BACKGROUND Lymphovascular invasion(LVI)and perineural invasion(PNI)are associated with decreased survival in colorectal cancer(CRC),but its significance in N1c stage remains to be clearly defined.AIM We retrospectivel...BACKGROUND Lymphovascular invasion(LVI)and perineural invasion(PNI)are associated with decreased survival in colorectal cancer(CRC),but its significance in N1c stage remains to be clearly defined.AIM We retrospectively identified 107 consecutive patients who had CRC with N1c disease radically resected at our hospital.Tumors were reviewed for LVI and PNI by one pathologist blinded to the patients’outcomes.Disease-free survival(DFS),overall survival(OS)and cancer-specific survival(CSS)were determined using the Kaplan-Meier method,with LVI and PNI prognosis differences determined by multivariate analysis using the Cox multiple hazards model.Results were compared using log-rank test.The receiver operating characteristic(ROC)curve was used to evaluate the prognostic predictive ability.RESULTS The median follow-up time was 63.17(45.33-81.37)months for DFS,with 33.64%(36/107)of patients experiencing recurrence;21.5%of tumors were found to be LVI positive and 44.9%PNI positive.The 5-year DFS rate was greater for patients with LVI-negative tumors compared with LVI-positive tumors(74.0%vs 35.6%),and PNI was similar(82.5%vs 45.1%).On multivariate analysis,LVI[hazard ratio(HR)=3.368,95%confidence interval(CI):1.628-6.966,P=0.001]and PNI(HR=3.055,95%CI:1.478-6.313,P=0.002)were independent prognostic factors for DFS.All patients could be divided into three groups of patients with different prognosis according to LVI and PNI.The 5-year ROC curve for LVI,PNI and their combination prediction of DFS was 0.646,0.709 and 0.759,respectively.Similar results were seen for OS and CSS.CONCLUSION LVI and PNI could serve as independent prognostic factors of outcomes in N1c CRC patients.Patients with LVI or PNI should be given more attention during treatment.展开更多
In order to better describe the phenomenon of biological invasion,this paper introduces a free boundary model of biological invasion.Firstly,the right free boundary is added to the equation with logistic terms.Secondl...In order to better describe the phenomenon of biological invasion,this paper introduces a free boundary model of biological invasion.Firstly,the right free boundary is added to the equation with logistic terms.Secondly,the existence and uniqueness of local solutions are proved by the Sobolev embedding theorem and the comparison principle.Finally,according to the relevant research data and contents of red fire ants,the diffusion area and nest number of red fire ants were simulated without external disturbance.This paper mainly simulates the early diffusion process of red fire ants.In the early diffusion stage,red fire ants grow slowly and then spread over a large area after reaching a certain number.展开更多
BACKGROUND Microvascular invasion(MVI)is a significant risk factor for recurrence and metastasis following hepatocellular carcinoma(HCC)surgery.Currently,there is a paucity of preoperative evaluation approaches for MV...BACKGROUND Microvascular invasion(MVI)is a significant risk factor for recurrence and metastasis following hepatocellular carcinoma(HCC)surgery.Currently,there is a paucity of preoperative evaluation approaches for MVI.AIM To investigate the predictive value of texture features and radiological signs based on multiparametric magnetic resonance imaging in the non-invasive preoperative prediction of MVI in HCC.METHODS Clinical data from 97 HCC patients were retrospectively collected from January 2019 to July 2022 at our hospital.Patients were classified into two groups:MVI-positive(n=57)and MVI-negative(n=40),based on postoperative pathological results.The correlation between relevant radiological signs and MVI status was analyzed.MaZda4.6 software and the mutual information method were employed to identify the top 10 dominant texture features,which were combined with radiological signs to construct artificial neural network(ANN)models for MVI prediction.The predictive performance of the ANN models was evaluated using area under the curve,sensitivity,and specificity.ANN models with relatively high predictive performance were screened using the DeLong test,and the regression model of multilayer feedforward ANN with backpropagation and error backpropagation learning method was used to evaluate the models’stability.RESULTS The absence of a pseudocapsule,an incomplete pseudocapsule,and the presence of tumor blood vessels were identified as independent predictors of HCC MVI.The ANN model constructed using the dominant features of the combined group(pseudocapsule status+tumor blood vessels+arterial phase+venous phase)demonstrated the best predictive performance for MVI status and was found to be automated,highly operable,and very stable.CONCLUSION The ANN model constructed using the dominant features of the combined group can be recommended as a noninvasive method for preoperative prediction of HCC MVI status.展开更多
BACKGROUND Glioblastoma multiforme(GBM)is the most aggressive and prevalent primary malignant brain tumor in adults,marked by poor prognosis and high invasiveness.Traditional GBM invasion assays,such as those involvin...BACKGROUND Glioblastoma multiforme(GBM)is the most aggressive and prevalent primary malignant brain tumor in adults,marked by poor prognosis and high invasiveness.Traditional GBM invasion assays,such as those involving mouse brain xenografts,are often time-consuming and limited in efficiency.In this context,stem cell-derived neural organoids(NOs)have emerged as advanced,threedimensional,human-relevant platforms that mimic the cellular architecture and microenvironment of the human brain.These models provide novel opportunities to investigate glioblastoma stem cell invasion,a critical driver of tumor progression and therapeutic resistance.AIM To evaluate studies using stem cell-derived NOs to model glioblastoma migration/invasion,focusing on methodologies,applications and therapeutic implications.METHODS We conducted a systematic review following PRISMA guidelines,searching PubMed and Scopus for studies published between March 2019 and March 2025 that investigated NOs in the context of glioblastoma invasion/migration.After screening 377 articles based on predefined inclusion and exclusion criteria,10 original research articles were selected for analysis.Extracted data were categorized into four analytical domains:(1)Tumor model formation;(2)NO characteristics;(3)NO differentiation protocols;and(4)Invasion/migration assessment methodologies.RESULTS The included studies exhibit significant methodological heterogeneity GBM model development,particularly regarding model type,cell source and culture conditions.Most studies(70%)used suspension cell models,while 30%employed spheroids,with most research focusing on patient-derived glioblastoma stem cells.NOs were predominantly generated from human induced pluripotent stem cells using both guided and unguided differentiation protocols.Confocal fluorescence microscopy was the primary method used for assessing invasion,revealing invasion depths of up to 300μm.Organoid maturity and co-culture duration influenced results,while key factors for model optimization included tumor cell density,organoid age and extracellular matrix composition.Some studies also tested therapeutic strategies such as Zika virus and microRNA modulation.Collectively,findings support the utility of NOs as effective tools for studying GBM behavior and therapeutic responses in a humanized three-dimensional context.CONCLUSION Human NOs represent promising platforms for modeling glioblastoma invasion in a humanized three-dimensional environment.However,a limited number of studies and methodological heterogeneity hinder reproducibility.Protocol standardization is essential to enhance the translational application of these models.展开更多
Following the publication,concerns have been raised about a number of figures in this article.The western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in man...Following the publication,concerns have been raised about a number of figures in this article.The western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.展开更多
The published article titled“lncRNA FEZF1-AS1 Is Associated with Prognosis in Lung Adenocarcinoma and Promotes Cell Proliferation,Migration,and Invasion”has been retracted from Oncology Research,Vol.27,No.1,2019,pp...The published article titled“lncRNA FEZF1-AS1 Is Associated with Prognosis in Lung Adenocarcinoma and Promotes Cell Proliferation,Migration,and Invasion”has been retracted from Oncology Research,Vol.27,No.1,2019,pp.39–45.展开更多
Published:18 July 2025 The published article titled“Inhibition of Liver Carcinoma Cell Invasion and Metastasis by Knockdown of Cullin7 In Vitro and In Vivo”has been retracted from Oncology Research,Vol.23,No.4,2015,...Published:18 July 2025 The published article titled“Inhibition of Liver Carcinoma Cell Invasion and Metastasis by Knockdown of Cullin7 In Vitro and In Vivo”has been retracted from Oncology Research,Vol.23,No.4,2015,pp.171–181.DOI:10.3727/096504016X14519995067562 URL:https://www.techscience.com/or/v23n4/57554 Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.In addition,the western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.展开更多
The published article titled“Swainsonine inhibits invasion and the EMT process in esophageal carcinoma cells by targeting twist1”has been retracted from Oncology Research,Vol.26,No.8,2018,pp.1207–1213.
Microvascular invasion(MVI)is a critical factor in hepatocellular carcinoma(HCC)prognosis,particularly in hepatitis B virus(HBV)-related cases.This editorial examines a recent study by Xu et al who developed models to...Microvascular invasion(MVI)is a critical factor in hepatocellular carcinoma(HCC)prognosis,particularly in hepatitis B virus(HBV)-related cases.This editorial examines a recent study by Xu et al who developed models to predict MVI and high-risk(M2)status in HBV-related HCC using contrast-enhanced computed tomography(CECT)radiomics and clinicoradiological factors.The study analyzed 270 patients,creating models that achieved an area under the curve values of 0.841 and 0.768 for MVI prediction,and 0.865 and 0.798 for M2 status prediction in training and validation datasets,respectively.These results are comparable to previous radiomics-based approaches,which reinforces the potential of this method in MVI prediction.The strengths of the study include its focus on HBV-related HCC and the use of widely accessible CECT imaging.However,limitations,such as retrospective design and manual segmentation,highlight areas for improvement.The editorial discusses the implications of the study including the need for standardized radiomics approaches and the potential impact on personalized treatment strategies.It also suggests future research directions,such as exploring mechanistic links between radiomics features and MVI,as well as integrating additional biomarkers or imaging modalities.Overall,this study contributes significantly to HCC management,paving the way for more accurate,personalized treatment approaches in the era of precision oncology.展开更多
BACKGROUND Liver transplant(LT)is one of the main treatment options in selected patients with hepatocellular carcinoma(HCC).Overall,macrovascular invasion has been shown to be associated with an increased risk of tumo...BACKGROUND Liver transplant(LT)is one of the main treatment options in selected patients with hepatocellular carcinoma(HCC).Overall,macrovascular invasion has been shown to be associated with an increased risk of tumor recurrence and mortality after LT in HCC.Macrovascular invasion detected on imaging is often considered a contraindication for LT in HCC.AIM To investigate the effect of macrovascular invasion in explant on post-LT survival in HCC patients using a large national transplant database in the United States.METHODS LT recipients with HCC between the years 2012 and 2022 were identified by using the United Network for Organ Sharing/Organ Procurement Transplant Network database.Patients who underwent deceased-donor LT with available liver explant pathology data were included.Kaplan-Meier curves were used for survival analysis,and multistep regression analysis was used to determine the predictors of mortality.RESULTS A total of 13638 LT recipients with HCC and available explant pathology were included.Of these,254(1.8%)showed macrovascular invasion,1712(12.6%)had microvascular invasion,and 11672(85.6%)had absent invasion.Poor tumor differentiation was more common with macrovascular invasion than with microvascular or absent invasion(22.4%,17.7%,and 5.1%,respectively,P<0.001).Post-transplant survival at 1 year,3 years,and 5 years was lower in the macrovascular group than in the microvascular and absent invasion cohort(83.6%,66.6%,55.7%vs 90.8%,76.2%,66.6%vs 93.9%,86.8%,80.7%,P<0.001).Similarly,transplant recipients whose explants were poorly differentiated had worse 1-year,3-year,and 5-year survival than those with well-differentiated tumors and those with complete necrosis(86.1%,67.1%,60.4%vs 94.3%,87.7%,81.9%vs 94.8%,89.7%,84.2%,P<0.001).In multivariable modeling,macrovascular invasion was associated with higher mortality risk compared to absent invasion[hazard ratio(HR)=2.3,95%CI:1.9–2.7],and poor differentiation carried greater mortality risk than complete necrosis(HR=2.3,95%CI:2.0–2.7).CONCLUSION Macrovascular invasion accounted for a minority of cases at 1.8%.Macrovascular invasion and poor tumor differentiation on liver explants in patients with HCC were associated with significantly higher post-LT mortality,meaning that the extent of tumor involvement and tumor biology are important predictors of post-LT survival in HCC.However,the overall 5-year survival in patients with macrovascular invasion may still be within an acceptable range.展开更多
BACKGROUND Microvascular invasion(MVI)is an important prognostic factor in hepatocellular carcinoma(HCC),but its preoperative prediction remains challenging.AIM To develop and validate a 2.5-dimensional(2.5D)deep lear...BACKGROUND Microvascular invasion(MVI)is an important prognostic factor in hepatocellular carcinoma(HCC),but its preoperative prediction remains challenging.AIM To develop and validate a 2.5-dimensional(2.5D)deep learning-based multiinstance learning(MIL)model(MIL signature)for predicting MVI in HCC,evaluate and compare its performance against the radiomics signature and clinical signature,and assess its prognostic predictive value in both surgical resection and transcatheter arterial chemoembolization(TACE)cohorts.METHODS A retrospective cohort consisting of 192 patients with pathologically confirmed HCC was included,of whom 68 were MVI-positive and 124 were MVI-negative.The patients were randomly assigned to a training set(134 patients)and a validation set(58 patients)in a 7:3 ratio.An additional 45 HCC patients undergoing TACE treatment were included in the TACE validation cohort.A modeling strategy based on computed tomography arterial phase images was implemented,utilizing 2.5D deep learning in combination with a MIL framework for the prediction of MVI in HCC.Moreover,this method was compared with the radiomics signature and clinical signatures,and the predictive performance of the various models was evaluated using receiver operating characteristic curves and decision curve analysis(DCA),with DeLong’s test applied to compare the area under the curve(AUC)between models.Kaplan-Meier curves were utilized to analyze differences in recurrence-free survival(RFS)or progression-free survival(PFS)among different HCC treatment cohorts stratified by MIL signature risk.RESULTS MIL signature demonstrated superior performance in the validation set(AUC=0.877),significantly surpassing the radiomics signature(AUC=0.727,P=0.047)and clinical signature(AUC=0.631,P=0.004).DCA curves indicated that the MIL signature provided a greater clinical net benefit across the full spectrum of risk thresholds.In the prognostic analysis,high-and low-risk groups stratified by the MIL signature exhibited significant differences in RFS within the surgical resection cohort(training set P=0.0058,validation set P=0.031)and PFS within the TACE treatment cohort(P=0.045).CONCLUSION MIL signature demonstrates more accurate MVI prediction in HCC,surpassing radiomics signature and clinical signature,and offers precise prognostic stratification,thereby providing new technical support for personalized HCC treatment strategies.展开更多
BACKGROUND Extramural venous invasion(EMVI)is a critical prognostic factor in gastric cancer(GC);however,its detection and underlying molecular mechanisms remain underexplored.AIM To investigate the relationship betwe...BACKGROUND Extramural venous invasion(EMVI)is a critical prognostic factor in gastric cancer(GC);however,its detection and underlying molecular mechanisms remain underexplored.AIM To investigate the relationship between EMVI and expression of the circular RNA hsa_circ_0097977 in orthotopic GC mouse models.METHODS A retrospective analysis was conducted in addition to a preclinical animal study,involving 13 GC patients and 24 orthotopic GC mouse models,respectively.EMVI was assessed using axial T2-weighted fat suppression sequences on a 9.4T magnetic resonance imaging(MRI)with histopathological confirmation as the gold standard for EMVI.The impact of hsa_circ_0097977 on EMVI and GC cell function was evaluated.Statistical analyses comprised consistency,area under the curve analysis,correlation,χ^(2)/Fisher exact,and Mann-Whitney U/t-tests,with significance set at P<0.05.RESULTS EMVI was accurately detected using 9.4T MRI in orthotopic mouse models with an area under the curve of 0.843(sensitivity 78.6%,specificity 90.0%).MRI detected EMVI was the only imaging factor associated with distant metastasis(P=0.04).Furthermore,knockdown of hsa_circ_0097977 was the only factor associated with EMVI(P=0.043,0.038)and led to reduced invasion and increased apoptosis in GC cells.CONCLUSION EMVI,a risk factor for distant metastasis in GC,is detectable by 9.4T MRI and regulated by hsa_circ_0097977,making it a potential therapeutic target.展开更多
Objective:Lymphovascular invasion(LVI)is a crucial step in metastasis and is closely associated with poor prognosis in patients with breast cancer.However,its clinical and molecular characteristics remain insufficient...Objective:Lymphovascular invasion(LVI)is a crucial step in metastasis and is closely associated with poor prognosis in patients with breast cancer.However,its clinical and molecular characteristics remain insufficiently defined.We aimed to identify molecular targets for LVI-positive(LVI+)breast cancer and predict patient prognosis via the analysis of genomic variations using targeted sequencing.Methods:We established a large-scale targeted sequencing cohort of 4,079 breast cancer samples,which included 3,159 early-stage and locally advanced patients with available LVI statuses.Comparisons of somatic mutation frequencies and germline pathogenic/likely pathogenic(P/LP)mutation frequencies,mutational signature analyses,and mutual exclusivity and co-occurrence analyses were performed to identify key genomic features involved in LVI+patients.Additionally,Kaplan-Meier survival analysis was conducted to further explore the prognostic value of co-mutations in LVI+cases.Results:We observed that LVI+patients with the hormone receptor-positive/human epidermal growth factor receptor 2-negative(HR+/HER2-)and triple-negative breast cancer(TNBC)subtypes exhibited worse disease-free survival.Notably,HR+/HER2-and HER2+breast cancer patients with LVI displayed distinct genomic features compared with LVI-tumors.Specifically,LVI+HR+/HER2-tumors exhibited greater frequencies of somatic mutations in TP53 and ESR1,germline BRCA2 P/LP variations,and an enrichment of clock-like single-base substitution(SBS)1 mutational signatures.In contrast,LVI+HER2+tumors demonstrated a higher incidence of somatic PIK3CA mutations and increased activity of the apolipoprotein B m RNA editing enzyme catalytic polypeptide(APOBEC)-associated SBS2 signature.Furthermore,we revealed that the co-mutation of TP53 and NF1 could serve as a potential prognostic marker for LVI+HR+/HER2-patients.Conclusions:Our findings provide a comprehensive overview of the genomic characteristics of LVI in breast cancer,thereby offering insights that may help in refining precision treatment strategies for LVI+breast cancer patients.展开更多
Published:18 July 2025 The published article titled“Knockdown of REV7 Inhibits Breast Cancer Cell Migration and Invasion”has been retracted from Oncology Research,Vol.24,No.5,2016,pp.315–325.DOI:10.3727/096504016X1...Published:18 July 2025 The published article titled“Knockdown of REV7 Inhibits Breast Cancer Cell Migration and Invasion”has been retracted from Oncology Research,Vol.24,No.5,2016,pp.315–325.DOI:10.3727/096504016X14666990347590 URL:https://www.techscience.com/or/v24n5/56980.Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.In addition,the western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.展开更多
Objective:Anillin(ANLN)is considered an oncogene in various cancers,but its effect on cervical cancer remains poorly understood.Hence,this study aimed to describe the action of ANLN on cervical cancer development and ...Objective:Anillin(ANLN)is considered an oncogene in various cancers,but its effect on cervical cancer remains poorly understood.Hence,this study aimed to describe the action of ANLN on cervical cancer development and investigate the potential mechanism.Methods:Analysis of ANLN expression and its association with survival in carcinoma and endocervical adenocarcinoma(CESC)patients based on GEO and UALCAN databases.The tumor and adjacent normal tissues of 100 cervical cancer cases were harvested to detect the ANLN expression and explore its relationship with patient survival.Cell proliferation,apoptosis,migration,and invasion were measured by utilizing 5-ethynyl-2′-deoxyuridine(EdU)staining,Flow cytometry,and Transwell assay,respectively.ANLN andWnt expression were analyzed by RT-qPCR andWestern Blot.Results:ANLN was significantly elevated in tumor tissues,and cervical cancer cases with high ANLN expression exhibited poor survival and high dead proportion.Besides,ANLN induced cervical cancer cell proliferation,migration,and invasion and restrained cell apoptosis.In addition,ANLN promoted Wnt/β-catenin pathway activation.Furthermore,ANLN accelerated cell aggressive behaviors and suppressed cell apoptosis via activating the Wnt/β-catenin signaling in cervical cancer.Conclusion:ANLN was enhanced in cervical cancer tissues and related to poor prognosis.ANLN accelerated cervical cancer cell aggressive behaviors and suppressed cell apoptosis via activating theWnt/β-catenin pathway.展开更多
BACKGROUND Microvascular invasion(MVI)is a critical prognostic factor for postoperative hepatocellular carcinoma recurrence,but the reliability of its current pathological diagnosis remains uncertain.AIM To evaluate t...BACKGROUND Microvascular invasion(MVI)is a critical prognostic factor for postoperative hepatocellular carcinoma recurrence,but the reliability of its current pathological diagnosis remains uncertain.AIM To evaluate the accuracy of current 7-point sampling methods and propose an optimal pathological protocol using whole-mount slide imaging(WSI)for better MVI detection.METHODS We utilized 40 New Zealand white rabbits to establish VX2 liver tumor models.The entire tumor-containing liver lobe was subsequently obtained,following which five different sampling protocols(A-E)were employed to evaluate the detection rate,accuracy,quantity,and distribution of MVI,with the aim of identifying the optimal sampling method.RESULTS VX2 liver tumor models were successfully established in 37 rabbits,with an incidence of MVI of 81.1%(30/37).The detection rates[27%(10/37),43%(16/37),62%(23/37),68%(25/37),and 93%(14/15)]and quantity(15,36,107,125,and 395)of MVI increased significantly from protocols A to E.The distribution of MVI showed fewer MVIs farther away from the tumor,but the percentage of MVI detected quantity gradually increased from 6.7%to 48.3%in the distant nonneoplastic liver tissue from protocols A to E.Protocol C was identified as the optimal sampling method by comparing them in sequence.The sampling protocol of three consecutive interval WSIs at the tumor center(WSI3)was further screened to determine the optimal number of WSIs.Protocol A(7-point sampling method)exhibited only 46%accuracy and a high false-negative rate of 67%.Notably,the WSI3 protocol improved the accuracy to 78%and decreased the false-negative rate to 27%.CONCLUSION The current 7-point sampling method has a high false-negative rate in MVI detection.In contrast,the WSI3 protocol provides a practical and effective approach to improve MVI diagnostic accuracy,which is crucial for hepatocellular carcinoma diagnosis and treatment planning.展开更多
This paper highlights the innovative approach and findings of the recently published study by Xu et al,which underscores the integration of radiomics and clinicoradiological factors to enhance the preoperative predict...This paper highlights the innovative approach and findings of the recently published study by Xu et al,which underscores the integration of radiomics and clinicoradiological factors to enhance the preoperative prediction of microvascular invasion in patients with hepatitis B virus-related hepatocellular carcinoma(HBV-HCC).The study’s use of contrast-enhanced computed tomography radiomics to construct predictive models offers a significant advancement in the surgical planning and management of HBV-HCC,potentially transforming patient outcomes through more personalized treatment strategies.This editorial commends the study's contribution to precision medicine and discusses its implic-ations for future research and clinical practice.展开更多
In the article“MicroRNA-101 Targets CXCL12-Mediated Akt and Snail Signaling Pathways to Inhibit Cellular Proliferation and Invasion in Papillary Thyroid Carcinoma”(Oncology Research.2019 Jun 21;27(6):691-701,doi:10....In the article“MicroRNA-101 Targets CXCL12-Mediated Akt and Snail Signaling Pathways to Inhibit Cellular Proliferation and Invasion in Papillary Thyroid Carcinoma”(Oncology Research.2019 Jun 21;27(6):691-701,doi:10.3727/096504018X15426763753594),the IHC images for CXCL12 and Bcl-2 expressions in adjacent noncancer tissues(NCT)shown in Fig.5E were unintentionally duplicated.And Fig.5A,B was also unintentionally duplicated.These needed corrections to ensure the accuracy and integrity of the data presented.展开更多
Perineural invasion(PNI)by tumor cells is a key phenotype of highly-invasive oral squamous cell carcinoma(OSCC).Since Schwann cells(SCs)and fibroblasts maintain the physiological homeostasis of the peripheral nervous ...Perineural invasion(PNI)by tumor cells is a key phenotype of highly-invasive oral squamous cell carcinoma(OSCC).Since Schwann cells(SCs)and fibroblasts maintain the physiological homeostasis of the peripheral nervous system,and we have focused on cancer-associated fibroblasts(CAFs)for decades,it’s imperative to elucidate the impact of CAFs on SCs in PNI+OSCCs.We describe a disease progression-driven shift of PNI−towards PNI+during the progression of early-stage OSCC(31%,n=125)to late-stage OSCC(53%,n=97),characterized by abundant CAFs and nerve demyelination.CAFs inhibited SC proliferation/migration and reduced neurotrophic factors and myelin in vitro,and this involved up-regulated ER stress and decreased MAPK signals.Moreover,CAFs also aggravated the paralysis of the hind limb and PNI in vivo.Unexpectedly,leukemia inhibitory factor(LIF)was exclusively expressed on CAFs and up-regulated in metastatic OSCC.The LIF inhibitor EC330 restored CAF-induced SC inactivation.Thus,OSCC-derived CAFs inactivate SCs to aggravate nerve injury and PNI development.展开更多
基金Supported by the National High Level Hospital Clinical Research Funding,No.2023-NHLHCRF-BQ-32 and No.2023-NHLHCRFYYPPLC-ZR-13the Elite Medical Professionals Project of China-Japan Friendship Hospital,No.ZRJY2024-GG01.
文摘BACKGROUND Lymphovascular invasion(LVI)and perineural invasion(PNI)are associated with decreased survival in colorectal cancer(CRC),but its significance in N1c stage remains to be clearly defined.AIM We retrospectively identified 107 consecutive patients who had CRC with N1c disease radically resected at our hospital.Tumors were reviewed for LVI and PNI by one pathologist blinded to the patients’outcomes.Disease-free survival(DFS),overall survival(OS)and cancer-specific survival(CSS)were determined using the Kaplan-Meier method,with LVI and PNI prognosis differences determined by multivariate analysis using the Cox multiple hazards model.Results were compared using log-rank test.The receiver operating characteristic(ROC)curve was used to evaluate the prognostic predictive ability.RESULTS The median follow-up time was 63.17(45.33-81.37)months for DFS,with 33.64%(36/107)of patients experiencing recurrence;21.5%of tumors were found to be LVI positive and 44.9%PNI positive.The 5-year DFS rate was greater for patients with LVI-negative tumors compared with LVI-positive tumors(74.0%vs 35.6%),and PNI was similar(82.5%vs 45.1%).On multivariate analysis,LVI[hazard ratio(HR)=3.368,95%confidence interval(CI):1.628-6.966,P=0.001]and PNI(HR=3.055,95%CI:1.478-6.313,P=0.002)were independent prognostic factors for DFS.All patients could be divided into three groups of patients with different prognosis according to LVI and PNI.The 5-year ROC curve for LVI,PNI and their combination prediction of DFS was 0.646,0.709 and 0.759,respectively.Similar results were seen for OS and CSS.CONCLUSION LVI and PNI could serve as independent prognostic factors of outcomes in N1c CRC patients.Patients with LVI or PNI should be given more attention during treatment.
基金Supported by National Natural Science Foundation of China(12101482)Postdoctoral Science Foundation of China(2022M722604)+2 种基金General Project of Science and Technology of Shaanxi Province(2023-YBSF-372)The Natural Science Foundation of Shaan Xi Province(2023-JCQN-0016)Shannxi Mathmatical Basic Science Research Project(23JSQ042)。
文摘In order to better describe the phenomenon of biological invasion,this paper introduces a free boundary model of biological invasion.Firstly,the right free boundary is added to the equation with logistic terms.Secondly,the existence and uniqueness of local solutions are proved by the Sobolev embedding theorem and the comparison principle.Finally,according to the relevant research data and contents of red fire ants,the diffusion area and nest number of red fire ants were simulated without external disturbance.This paper mainly simulates the early diffusion process of red fire ants.In the early diffusion stage,red fire ants grow slowly and then spread over a large area after reaching a certain number.
基金Supported by the National Natural Science Foundation of China,No.81560278the Health Commission of Guangxi Zhuang Autonomous Region,No.Z20200953,No.G201903023,and No.Z-A20221157Scientific Research and Technology Development Project of Nanning,No.20213122.
文摘BACKGROUND Microvascular invasion(MVI)is a significant risk factor for recurrence and metastasis following hepatocellular carcinoma(HCC)surgery.Currently,there is a paucity of preoperative evaluation approaches for MVI.AIM To investigate the predictive value of texture features and radiological signs based on multiparametric magnetic resonance imaging in the non-invasive preoperative prediction of MVI in HCC.METHODS Clinical data from 97 HCC patients were retrospectively collected from January 2019 to July 2022 at our hospital.Patients were classified into two groups:MVI-positive(n=57)and MVI-negative(n=40),based on postoperative pathological results.The correlation between relevant radiological signs and MVI status was analyzed.MaZda4.6 software and the mutual information method were employed to identify the top 10 dominant texture features,which were combined with radiological signs to construct artificial neural network(ANN)models for MVI prediction.The predictive performance of the ANN models was evaluated using area under the curve,sensitivity,and specificity.ANN models with relatively high predictive performance were screened using the DeLong test,and the regression model of multilayer feedforward ANN with backpropagation and error backpropagation learning method was used to evaluate the models’stability.RESULTS The absence of a pseudocapsule,an incomplete pseudocapsule,and the presence of tumor blood vessels were identified as independent predictors of HCC MVI.The ANN model constructed using the dominant features of the combined group(pseudocapsule status+tumor blood vessels+arterial phase+venous phase)demonstrated the best predictive performance for MVI status and was found to be automated,highly operable,and very stable.CONCLUSION The ANN model constructed using the dominant features of the combined group can be recommended as a noninvasive method for preoperative prediction of HCC MVI status.
基金Supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico,No.307318/2023-0 and No.102035/2024-5Fundação de AmparoàPesquisa do Estado de São Paulo,No.2023/10843-7 and No 2019/21070-3Nanotechnology National Laboratory System 2.0,Ministry of Science,Technology,Innovation and Communication,No.442539/2019-3.
文摘BACKGROUND Glioblastoma multiforme(GBM)is the most aggressive and prevalent primary malignant brain tumor in adults,marked by poor prognosis and high invasiveness.Traditional GBM invasion assays,such as those involving mouse brain xenografts,are often time-consuming and limited in efficiency.In this context,stem cell-derived neural organoids(NOs)have emerged as advanced,threedimensional,human-relevant platforms that mimic the cellular architecture and microenvironment of the human brain.These models provide novel opportunities to investigate glioblastoma stem cell invasion,a critical driver of tumor progression and therapeutic resistance.AIM To evaluate studies using stem cell-derived NOs to model glioblastoma migration/invasion,focusing on methodologies,applications and therapeutic implications.METHODS We conducted a systematic review following PRISMA guidelines,searching PubMed and Scopus for studies published between March 2019 and March 2025 that investigated NOs in the context of glioblastoma invasion/migration.After screening 377 articles based on predefined inclusion and exclusion criteria,10 original research articles were selected for analysis.Extracted data were categorized into four analytical domains:(1)Tumor model formation;(2)NO characteristics;(3)NO differentiation protocols;and(4)Invasion/migration assessment methodologies.RESULTS The included studies exhibit significant methodological heterogeneity GBM model development,particularly regarding model type,cell source and culture conditions.Most studies(70%)used suspension cell models,while 30%employed spheroids,with most research focusing on patient-derived glioblastoma stem cells.NOs were predominantly generated from human induced pluripotent stem cells using both guided and unguided differentiation protocols.Confocal fluorescence microscopy was the primary method used for assessing invasion,revealing invasion depths of up to 300μm.Organoid maturity and co-culture duration influenced results,while key factors for model optimization included tumor cell density,organoid age and extracellular matrix composition.Some studies also tested therapeutic strategies such as Zika virus and microRNA modulation.Collectively,findings support the utility of NOs as effective tools for studying GBM behavior and therapeutic responses in a humanized three-dimensional context.CONCLUSION Human NOs represent promising platforms for modeling glioblastoma invasion in a humanized three-dimensional environment.However,a limited number of studies and methodological heterogeneity hinder reproducibility.Protocol standardization is essential to enhance the translational application of these models.
文摘Following the publication,concerns have been raised about a number of figures in this article.The western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.
文摘The published article titled“lncRNA FEZF1-AS1 Is Associated with Prognosis in Lung Adenocarcinoma and Promotes Cell Proliferation,Migration,and Invasion”has been retracted from Oncology Research,Vol.27,No.1,2019,pp.39–45.
文摘Published:18 July 2025 The published article titled“Inhibition of Liver Carcinoma Cell Invasion and Metastasis by Knockdown of Cullin7 In Vitro and In Vivo”has been retracted from Oncology Research,Vol.23,No.4,2015,pp.171–181.DOI:10.3727/096504016X14519995067562 URL:https://www.techscience.com/or/v23n4/57554 Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.In addition,the western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.
文摘The published article titled“Swainsonine inhibits invasion and the EMT process in esophageal carcinoma cells by targeting twist1”has been retracted from Oncology Research,Vol.26,No.8,2018,pp.1207–1213.
文摘Microvascular invasion(MVI)is a critical factor in hepatocellular carcinoma(HCC)prognosis,particularly in hepatitis B virus(HBV)-related cases.This editorial examines a recent study by Xu et al who developed models to predict MVI and high-risk(M2)status in HBV-related HCC using contrast-enhanced computed tomography(CECT)radiomics and clinicoradiological factors.The study analyzed 270 patients,creating models that achieved an area under the curve values of 0.841 and 0.768 for MVI prediction,and 0.865 and 0.798 for M2 status prediction in training and validation datasets,respectively.These results are comparable to previous radiomics-based approaches,which reinforces the potential of this method in MVI prediction.The strengths of the study include its focus on HBV-related HCC and the use of widely accessible CECT imaging.However,limitations,such as retrospective design and manual segmentation,highlight areas for improvement.The editorial discusses the implications of the study including the need for standardized radiomics approaches and the potential impact on personalized treatment strategies.It also suggests future research directions,such as exploring mechanistic links between radiomics features and MVI,as well as integrating additional biomarkers or imaging modalities.Overall,this study contributes significantly to HCC management,paving the way for more accurate,personalized treatment approaches in the era of precision oncology.
文摘BACKGROUND Liver transplant(LT)is one of the main treatment options in selected patients with hepatocellular carcinoma(HCC).Overall,macrovascular invasion has been shown to be associated with an increased risk of tumor recurrence and mortality after LT in HCC.Macrovascular invasion detected on imaging is often considered a contraindication for LT in HCC.AIM To investigate the effect of macrovascular invasion in explant on post-LT survival in HCC patients using a large national transplant database in the United States.METHODS LT recipients with HCC between the years 2012 and 2022 were identified by using the United Network for Organ Sharing/Organ Procurement Transplant Network database.Patients who underwent deceased-donor LT with available liver explant pathology data were included.Kaplan-Meier curves were used for survival analysis,and multistep regression analysis was used to determine the predictors of mortality.RESULTS A total of 13638 LT recipients with HCC and available explant pathology were included.Of these,254(1.8%)showed macrovascular invasion,1712(12.6%)had microvascular invasion,and 11672(85.6%)had absent invasion.Poor tumor differentiation was more common with macrovascular invasion than with microvascular or absent invasion(22.4%,17.7%,and 5.1%,respectively,P<0.001).Post-transplant survival at 1 year,3 years,and 5 years was lower in the macrovascular group than in the microvascular and absent invasion cohort(83.6%,66.6%,55.7%vs 90.8%,76.2%,66.6%vs 93.9%,86.8%,80.7%,P<0.001).Similarly,transplant recipients whose explants were poorly differentiated had worse 1-year,3-year,and 5-year survival than those with well-differentiated tumors and those with complete necrosis(86.1%,67.1%,60.4%vs 94.3%,87.7%,81.9%vs 94.8%,89.7%,84.2%,P<0.001).In multivariable modeling,macrovascular invasion was associated with higher mortality risk compared to absent invasion[hazard ratio(HR)=2.3,95%CI:1.9–2.7],and poor differentiation carried greater mortality risk than complete necrosis(HR=2.3,95%CI:2.0–2.7).CONCLUSION Macrovascular invasion accounted for a minority of cases at 1.8%.Macrovascular invasion and poor tumor differentiation on liver explants in patients with HCC were associated with significantly higher post-LT mortality,meaning that the extent of tumor involvement and tumor biology are important predictors of post-LT survival in HCC.However,the overall 5-year survival in patients with macrovascular invasion may still be within an acceptable range.
基金Supported by the National Natural Science Foundation of China,No.81560278The“Summit Plan(New Departure)”Project for the Development of Doctoral Degree Authorization Points and Professional Disciplines at the Affiliated Hospital of Youjiang Medical University for Nationalities,No.DF20244433+1 种基金Self-funded Research Project by the Guangxi Health and Wellness Committee,No.ZL20240824 and No.Z-L20240834The Project to Enhance the Research Foundations of Young and Mid-career Faculty in Guangxi Universities,No.2024KY0562 and No.2024KY0559。
文摘BACKGROUND Microvascular invasion(MVI)is an important prognostic factor in hepatocellular carcinoma(HCC),but its preoperative prediction remains challenging.AIM To develop and validate a 2.5-dimensional(2.5D)deep learning-based multiinstance learning(MIL)model(MIL signature)for predicting MVI in HCC,evaluate and compare its performance against the radiomics signature and clinical signature,and assess its prognostic predictive value in both surgical resection and transcatheter arterial chemoembolization(TACE)cohorts.METHODS A retrospective cohort consisting of 192 patients with pathologically confirmed HCC was included,of whom 68 were MVI-positive and 124 were MVI-negative.The patients were randomly assigned to a training set(134 patients)and a validation set(58 patients)in a 7:3 ratio.An additional 45 HCC patients undergoing TACE treatment were included in the TACE validation cohort.A modeling strategy based on computed tomography arterial phase images was implemented,utilizing 2.5D deep learning in combination with a MIL framework for the prediction of MVI in HCC.Moreover,this method was compared with the radiomics signature and clinical signatures,and the predictive performance of the various models was evaluated using receiver operating characteristic curves and decision curve analysis(DCA),with DeLong’s test applied to compare the area under the curve(AUC)between models.Kaplan-Meier curves were utilized to analyze differences in recurrence-free survival(RFS)or progression-free survival(PFS)among different HCC treatment cohorts stratified by MIL signature risk.RESULTS MIL signature demonstrated superior performance in the validation set(AUC=0.877),significantly surpassing the radiomics signature(AUC=0.727,P=0.047)and clinical signature(AUC=0.631,P=0.004).DCA curves indicated that the MIL signature provided a greater clinical net benefit across the full spectrum of risk thresholds.In the prognostic analysis,high-and low-risk groups stratified by the MIL signature exhibited significant differences in RFS within the surgical resection cohort(training set P=0.0058,validation set P=0.031)and PFS within the TACE treatment cohort(P=0.045).CONCLUSION MIL signature demonstrates more accurate MVI prediction in HCC,surpassing radiomics signature and clinical signature,and offers precise prognostic stratification,thereby providing new technical support for personalized HCC treatment strategies.
基金Supported by The National Natural Science Foundation of China,No.81901819Peking University People’s Hospital Scientific Research Development Funds,No.RDX2024-08Beijing Natural Science Foundation,No.7232187.
文摘BACKGROUND Extramural venous invasion(EMVI)is a critical prognostic factor in gastric cancer(GC);however,its detection and underlying molecular mechanisms remain underexplored.AIM To investigate the relationship between EMVI and expression of the circular RNA hsa_circ_0097977 in orthotopic GC mouse models.METHODS A retrospective analysis was conducted in addition to a preclinical animal study,involving 13 GC patients and 24 orthotopic GC mouse models,respectively.EMVI was assessed using axial T2-weighted fat suppression sequences on a 9.4T magnetic resonance imaging(MRI)with histopathological confirmation as the gold standard for EMVI.The impact of hsa_circ_0097977 on EMVI and GC cell function was evaluated.Statistical analyses comprised consistency,area under the curve analysis,correlation,χ^(2)/Fisher exact,and Mann-Whitney U/t-tests,with significance set at P<0.05.RESULTS EMVI was accurately detected using 9.4T MRI in orthotopic mouse models with an area under the curve of 0.843(sensitivity 78.6%,specificity 90.0%).MRI detected EMVI was the only imaging factor associated with distant metastasis(P=0.04).Furthermore,knockdown of hsa_circ_0097977 was the only factor associated with EMVI(P=0.043,0.038)and led to reduced invasion and increased apoptosis in GC cells.CONCLUSION EMVI,a risk factor for distant metastasis in GC,is detectable by 9.4T MRI and regulated by hsa_circ_0097977,making it a potential therapeutic target.
基金supported by grants from the National Natural Science Foundation of China(No.82373303,No.82072922,No.82403750)a grant from the Natural Science Foundation of Shanghai(No.24ZR1412600)。
文摘Objective:Lymphovascular invasion(LVI)is a crucial step in metastasis and is closely associated with poor prognosis in patients with breast cancer.However,its clinical and molecular characteristics remain insufficiently defined.We aimed to identify molecular targets for LVI-positive(LVI+)breast cancer and predict patient prognosis via the analysis of genomic variations using targeted sequencing.Methods:We established a large-scale targeted sequencing cohort of 4,079 breast cancer samples,which included 3,159 early-stage and locally advanced patients with available LVI statuses.Comparisons of somatic mutation frequencies and germline pathogenic/likely pathogenic(P/LP)mutation frequencies,mutational signature analyses,and mutual exclusivity and co-occurrence analyses were performed to identify key genomic features involved in LVI+patients.Additionally,Kaplan-Meier survival analysis was conducted to further explore the prognostic value of co-mutations in LVI+cases.Results:We observed that LVI+patients with the hormone receptor-positive/human epidermal growth factor receptor 2-negative(HR+/HER2-)and triple-negative breast cancer(TNBC)subtypes exhibited worse disease-free survival.Notably,HR+/HER2-and HER2+breast cancer patients with LVI displayed distinct genomic features compared with LVI-tumors.Specifically,LVI+HR+/HER2-tumors exhibited greater frequencies of somatic mutations in TP53 and ESR1,germline BRCA2 P/LP variations,and an enrichment of clock-like single-base substitution(SBS)1 mutational signatures.In contrast,LVI+HER2+tumors demonstrated a higher incidence of somatic PIK3CA mutations and increased activity of the apolipoprotein B m RNA editing enzyme catalytic polypeptide(APOBEC)-associated SBS2 signature.Furthermore,we revealed that the co-mutation of TP53 and NF1 could serve as a potential prognostic marker for LVI+HR+/HER2-patients.Conclusions:Our findings provide a comprehensive overview of the genomic characteristics of LVI in breast cancer,thereby offering insights that may help in refining precision treatment strategies for LVI+breast cancer patients.
文摘Published:18 July 2025 The published article titled“Knockdown of REV7 Inhibits Breast Cancer Cell Migration and Invasion”has been retracted from Oncology Research,Vol.24,No.5,2016,pp.315–325.DOI:10.3727/096504016X14666990347590 URL:https://www.techscience.com/or/v24n5/56980.Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.In addition,the western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.
文摘Objective:Anillin(ANLN)is considered an oncogene in various cancers,but its effect on cervical cancer remains poorly understood.Hence,this study aimed to describe the action of ANLN on cervical cancer development and investigate the potential mechanism.Methods:Analysis of ANLN expression and its association with survival in carcinoma and endocervical adenocarcinoma(CESC)patients based on GEO and UALCAN databases.The tumor and adjacent normal tissues of 100 cervical cancer cases were harvested to detect the ANLN expression and explore its relationship with patient survival.Cell proliferation,apoptosis,migration,and invasion were measured by utilizing 5-ethynyl-2′-deoxyuridine(EdU)staining,Flow cytometry,and Transwell assay,respectively.ANLN andWnt expression were analyzed by RT-qPCR andWestern Blot.Results:ANLN was significantly elevated in tumor tissues,and cervical cancer cases with high ANLN expression exhibited poor survival and high dead proportion.Besides,ANLN induced cervical cancer cell proliferation,migration,and invasion and restrained cell apoptosis.In addition,ANLN promoted Wnt/β-catenin pathway activation.Furthermore,ANLN accelerated cell aggressive behaviors and suppressed cell apoptosis via activating the Wnt/β-catenin signaling in cervical cancer.Conclusion:ANLN was enhanced in cervical cancer tissues and related to poor prognosis.ANLN accelerated cervical cancer cell aggressive behaviors and suppressed cell apoptosis via activating theWnt/β-catenin pathway.
基金Supported by the National Natural Science Foundation of China,No.82072038 and No.82371975.
文摘BACKGROUND Microvascular invasion(MVI)is a critical prognostic factor for postoperative hepatocellular carcinoma recurrence,but the reliability of its current pathological diagnosis remains uncertain.AIM To evaluate the accuracy of current 7-point sampling methods and propose an optimal pathological protocol using whole-mount slide imaging(WSI)for better MVI detection.METHODS We utilized 40 New Zealand white rabbits to establish VX2 liver tumor models.The entire tumor-containing liver lobe was subsequently obtained,following which five different sampling protocols(A-E)were employed to evaluate the detection rate,accuracy,quantity,and distribution of MVI,with the aim of identifying the optimal sampling method.RESULTS VX2 liver tumor models were successfully established in 37 rabbits,with an incidence of MVI of 81.1%(30/37).The detection rates[27%(10/37),43%(16/37),62%(23/37),68%(25/37),and 93%(14/15)]and quantity(15,36,107,125,and 395)of MVI increased significantly from protocols A to E.The distribution of MVI showed fewer MVIs farther away from the tumor,but the percentage of MVI detected quantity gradually increased from 6.7%to 48.3%in the distant nonneoplastic liver tissue from protocols A to E.Protocol C was identified as the optimal sampling method by comparing them in sequence.The sampling protocol of three consecutive interval WSIs at the tumor center(WSI3)was further screened to determine the optimal number of WSIs.Protocol A(7-point sampling method)exhibited only 46%accuracy and a high false-negative rate of 67%.Notably,the WSI3 protocol improved the accuracy to 78%and decreased the false-negative rate to 27%.CONCLUSION The current 7-point sampling method has a high false-negative rate in MVI detection.In contrast,the WSI3 protocol provides a practical and effective approach to improve MVI diagnostic accuracy,which is crucial for hepatocellular carcinoma diagnosis and treatment planning.
基金Supported by Shandong Province Medical and Health Science and Technology Development Plan Project,No.202203030713Science and Technology Program of Yantai Affiliated Hospital of Binzhou Medical University,No.YTFY2022KYQD06。
文摘This paper highlights the innovative approach and findings of the recently published study by Xu et al,which underscores the integration of radiomics and clinicoradiological factors to enhance the preoperative prediction of microvascular invasion in patients with hepatitis B virus-related hepatocellular carcinoma(HBV-HCC).The study’s use of contrast-enhanced computed tomography radiomics to construct predictive models offers a significant advancement in the surgical planning and management of HBV-HCC,potentially transforming patient outcomes through more personalized treatment strategies.This editorial commends the study's contribution to precision medicine and discusses its implic-ations for future research and clinical practice.
文摘In the article“MicroRNA-101 Targets CXCL12-Mediated Akt and Snail Signaling Pathways to Inhibit Cellular Proliferation and Invasion in Papillary Thyroid Carcinoma”(Oncology Research.2019 Jun 21;27(6):691-701,doi:10.3727/096504018X15426763753594),the IHC images for CXCL12 and Bcl-2 expressions in adjacent noncancer tissues(NCT)shown in Fig.5E were unintentionally duplicated.And Fig.5A,B was also unintentionally duplicated.These needed corrections to ensure the accuracy and integrity of the data presented.
基金supported by the National Natural Science Foundation of China(82373037 and 82403486)the Natural Science Foundation of Jiangsu Province(BK20230054 and BK20230161)+1 种基金the China Postdoctoral Science Foundation(2023M741766)the Nanjing Medical Science and Technology Development Foundation,Nanjing Department of Health(YKK21182 and JQX23010).
文摘Perineural invasion(PNI)by tumor cells is a key phenotype of highly-invasive oral squamous cell carcinoma(OSCC).Since Schwann cells(SCs)and fibroblasts maintain the physiological homeostasis of the peripheral nervous system,and we have focused on cancer-associated fibroblasts(CAFs)for decades,it’s imperative to elucidate the impact of CAFs on SCs in PNI+OSCCs.We describe a disease progression-driven shift of PNI−towards PNI+during the progression of early-stage OSCC(31%,n=125)to late-stage OSCC(53%,n=97),characterized by abundant CAFs and nerve demyelination.CAFs inhibited SC proliferation/migration and reduced neurotrophic factors and myelin in vitro,and this involved up-regulated ER stress and decreased MAPK signals.Moreover,CAFs also aggravated the paralysis of the hind limb and PNI in vivo.Unexpectedly,leukemia inhibitory factor(LIF)was exclusively expressed on CAFs and up-regulated in metastatic OSCC.The LIF inhibitor EC330 restored CAF-induced SC inactivation.Thus,OSCC-derived CAFs inactivate SCs to aggravate nerve injury and PNI development.
