Nasopharyngeal carcinoma(NPC)is a malignant tumor prevalent in southern China and Southeast Asia,where its early detection is crucial for improving patient prognosis and reducing mortality rates.However,existing scree...Nasopharyngeal carcinoma(NPC)is a malignant tumor prevalent in southern China and Southeast Asia,where its early detection is crucial for improving patient prognosis and reducing mortality rates.However,existing screening methods suffer from limitations in accuracy and accessibility,hindering their application in large-scale population screening.In this work,a surface-enhanced Raman spectroscopy(SERS)-based method was established to explore the profiles of different stratified components in saliva from NPC and healthy subjects after fractionation processing.The study findings indicate that all fractionated samples exhibit diseaseassociated molecular signaling differences,where small-molecule(molecular weight cut-offvalue is 10 kDa)demonstrating superior classification capabilities with sensitivity of 90.5%and speci-ficity of 75.6%,area under receiver operating characteristic(ROC)curve of 0:925±0:031.The primary objective of this study was to qualitatively explore patterns in saliva composition across groups.The proposed SERS detection strategy for fractionated saliva offers novel insights for enhancing the sensitivity and reliability of noninvasive NPC screening,laying the foundation for translational application in large-scale clinical settings.展开更多
BACKGROUND Bone is a major site of metastasis in nasopharyngeal carcinoma(NPC).Recently,nuclear factor kappa-beta ligand(RANKL)inhibitors have garnered attention for their ability to inhibit osteoclast formation and b...BACKGROUND Bone is a major site of metastasis in nasopharyngeal carcinoma(NPC).Recently,nuclear factor kappa-beta ligand(RANKL)inhibitors have garnered attention for their ability to inhibit osteoclast formation and bone resorption,as well as their potential to modulate immune functions and thereby enhance the efficacy of programmed cell death protein 1(PD-1)inhibitor therapy.CASE SUMMARY We present a case of a patient with NPC who developed sternal stalk metastasis and multiple bone metastases with soft tissue invasion following radical chemoradiotherapy and targeted therapy.Prior to chemotherapy,the patient experienced severe bone marrow suppression and opted out of further chemotherapy sessions.However,the patient received combination therapy,including RANKL inhibitors(denosumab)alongside PD-1,radiotherapy,and granulocyte-macrophage colonystimulating factor(PRaG)therapy(NCT05435768),and achieved 16 months of progression-free survival and more than 35 months of overall survival,without encountering any grade 2 or higher treatment-related adverse events.CONCLUSION Denosumab combined with PRaG therapy could be a new therapeutic approach for the second-line treatment in patients with bone metastases.展开更多
Objective:To investigate the chemical components of Semen podocarpi extract(SPE)and its effect on nasopharyngeal carcinoma cells and CNE-2R cells.Methods:Chemical components in SPE were identified by UPLC-MS/MS.CCK-8 ...Objective:To investigate the chemical components of Semen podocarpi extract(SPE)and its effect on nasopharyngeal carcinoma cells and CNE-2R cells.Methods:Chemical components in SPE were identified by UPLC-MS/MS.CCK-8 and cell cloning experiments were applied to evaluate the effects of SPE on the proliferation of CNE-2R cells,and a single-hit multitarget model was used to calculate the radiobiological parameters.Cell apoptosis and cell cycle were analyzed by flow cytometry,and the levels of genes and proteins of the Raf/MEK/ERK pathway were determined by RT-PCR and Western blotting.Results:A total of 37 compounds from SPE were identified,and SPE with or without irradiation inhibited the proliferation of CNE-2R cells.SPE also promoted apoptosis,arrested cells in the G_(2)/M phase,and presented radiosensitizing effects.Compared with irradiation alone,the effects of SPE+irradiation on apoptosis and cell cycle distribution were not significantly different.In addition,SPE had no significant effect on MEK gene expression.SPE significantly increased the gene expression of C-Raf and significantly reduced the protein expression of C-Raf,as well as the gene and protein expression of ERK1 and ERK2.The protein levels of C-Raf,ERK1,and ERK2 were also significantly lower in cells treated with SPE+irradiation than in cells treated with irradiation alone.Conclusions:The effects of SPE on inhibiting cell proliferation and promoting apoptosis are likely associated with cell cycle arrest and Raf/MEK/ERK pathway regulation,and the mechanism underlying radiosensitization by SPE may involve downregulating the protein expression of C-Raf,ERK1,and ERK2.展开更多
Filopodia function as cellular sensors,detecting the microenvironment and directing cell migration.They play a crucial role in cancer metastasis.Quantifying the filopodia characteristics of cancer cells is a prerequis...Filopodia function as cellular sensors,detecting the microenvironment and directing cell migration.They play a crucial role in cancer metastasis.Quantifying the filopodia characteristics of cancer cells is a prerequisite for studying the complex role of filopodia in cancer cell metastasis.Several algorithms have been developed,yet most of these algorithms are typically suited for extracting filopodia from individual cells.This paper aims to develop an independent algorithm(MC-FiloAssay)for quantifying filopodia in multi-cell environments.The filopodia of nasopharyngeal carcinoma cells(CNE2 and 5-8F)and normal nasopharyngeal epithelial cells(NP69)were quantified with MC-FiloAssay.A linear regression analysis comparing filopodia lengths measured by MC-FiloAssay and manual annotation yielded a coefficient of determination(R^(2)=0.99),indicating high accuracy in multi-cell filopodia extraction.Furthermore,MC-FiloAssay outperforms existing algorithms under low signal conditions and in multi-cell fields of view.Analysis of CNE2 cells at different confluences revealed that confluence does not affect filopodia length or width but influences filopodia density.Additionally,significant differences were observed between CNE2 and the other two cell lines(5-8 F and NP69):CNE2 filopodia were longer,thinner,and more densely distributed.These results demonstrate that MCFiloAssay is a robust tool for multi-cell filopodia quantification.展开更多
Various genetic association studies have identified numerous single nucleotide polymorphisms(SNPs)associated with nasopharyngeal carcinoma(NPC)risk.However,these studies have predominantly focused on common variants,l...Various genetic association studies have identified numerous single nucleotide polymorphisms(SNPs)associated with nasopharyngeal carcinoma(NPC)risk.However,these studies have predominantly focused on common variants,leaving the contribution of rare variants to the“missing heritability”largely unexplored.Here,we integrate genotyping data from 3925 NPC cases and 15,048 healthy controls to identify a rare SNP,rs141121474,resulting in a Glu510Lys mutation in KLHDC4 gene linked to increased NPC risk.Subsequent analyses reveal that KLHDC4 is highly expressed in NPC and correlates with poorer prognosis.Functional characterizations demonstrate that KLHDC4 acts as an oncogene in NPC cells,enhancing their migratory and metastatic capabilities,with these effects being further augmented by the Glu510Lys mutation.Mechanistically,the Glu510Lys mutant exhibits increased interaction with Vimentin compared to the wild-type KLHDC4(KLHDC4-WT),leading to elevated Vimentin protein stability and modulation of the epithelial-mesenchymal transition process,thereby promoting tumor metastasis.Moreover,Vimentin knockdown significantly mitigates the oncogenic effects induced by overexpression of both KLHDC4-WT and the Glu510Lys variant.Collectively,our findings highlight the critical role of the rare KLHDC4 variant rs141121474 in NPC progression and propose its potential as a diagnostic and therapeutic target for NPC patients.展开更多
Objective:Radiotherapy(RT)is the definitive treatment for stageⅡnasopharyngeal carcinoma(NPC),which is classified as stagesⅠA andⅠB in the latest ninth edition of American Joint Committee on Cancer(AJCC)/Union for ...Objective:Radiotherapy(RT)is the definitive treatment for stageⅡnasopharyngeal carcinoma(NPC),which is classified as stagesⅠA andⅠB in the latest ninth edition of American Joint Committee on Cancer(AJCC)/Union for International Cancer Control(UICC).A crucial question is whether concurrent chemo-radiotherapy(CCRT)could derive additional benefits to this recent“down-staging”subgroup of NPC patients.This study aimed to interrogate clinical and radiomic features for predicting 5-year progression-free survival(PFS)of stageⅡNPC treated with RT alone or CCRT.Methods:Imaging and clinical data of 166 stageⅡNPC(eighth edition AJCC/UICC)patients were collected.Data were allocated into training,internal testing,and external testing sets.For each case,851 radiomic features were extracted and 10 clinical features were collected.Radiomic and clinical features most associated with the 5-year PFS were selected separately.A combined model was developed using multivariate logistic regression by integrating selected features and treatment option to predict 5-year PFS.Model performances were evaluated by area under the receiver operating curve(AUC),prediction accuracy,and decision curve analysis.Survival analyses including Kaplan-Meier analysis and Cox regression model were performed for further analysis.Results:Thirteen radiomic features,three clinical features,and treatment option were considered for model development.The combined model showed higher prognostic performance than using either.For the merged testing set(internal and external testing sets),AUC is 0.76(combined)vs.0.56-0.80(clinical or radiomic alone)and accuracy is 0.75(combined)vs.0.62-0.73(clinical or radiomic alone).Kaplan-Meier analysis using the combined model showed significant discrimination in PFS of the predicted low-risk and high-risk groups in the training and internal testing cohorts(P<0.05).Conclusions:Integrating with clinical and radiomic features could provide prognostic information on 5-year PFS under either treatment regimen,guiding individualized decisions of chemotherapy based on the predicted treatment outcome.展开更多
BACKGROUND Nasopharyngeal carcinoma(NPC),exhibiting high incidence in southern China,is linked to genetic and environmental factors.Vitamin D metabolism,involving transport[group-specific component(GC)protein]and acti...BACKGROUND Nasopharyngeal carcinoma(NPC),exhibiting high incidence in southern China,is linked to genetic and environmental factors.Vitamin D metabolism,involving transport[group-specific component(GC)protein]and activation[25-hydroxylase(CYP2R1)enzyme],may influence NPC susceptibility and radiotherapy response.Polymorphisms in GC and CYP2R1 genes affect protein function and serum 25-hydroxyvitamin D[25(OH)D]levels,and are implicated in other cancers.However,their role in NPC-particularly in high-risk Han Chinese populations-and interaction with vitamin D status remains unclear.This case control study(360 NPC patients,550 controls)investigates these relationships to inform prevention and personalized therapy.AIM To investigate the association between vitamin D binding protein(GC)and CYP2R1 gene polymorphisms with susceptibility to NPC and radiotherapy response.METHODS A case control study design was adopted,and 360 patients with NPC and 550 healthy controls were included.TaqMan method was used to perform genotyping on GC gene loci rs4588,rs7041,and CYP2R1 gene loci rs10741657,rs12794714.Serum 25(OH)D levels were detected,and the relationship between gene polymorphisms and NPC risk and radiotherapy response was analyzed.RESULTS The GC gene rs4588 TT genotype was significantly associated with the risk of NPC in both the codominant model[odds ratio(OR)=1.68,95%CI:1.15-2.45,P=0.007]and the recessive model(OR=1.56,95%CI:1.02-2.38,P=0.039).The association between the rs4588 TT genotype and the risk of NPC was more significant in the male subgroup(OR=1.87,95%CI:1.11-3.15,P=0.019)and the squamous cell carcinoma subgroup(OR=1.89,95%CI:1.19-3.00,P=0.007).The serum 25(OH)D level of the rs7041 AA genotype carriers was significantly lower than that of the CC genotype(P<0.001).The CYP2R1 gene rs10741657 AA genotype was associated with higher serum 25(OH)D levels(P=0.003).The rs12794714 AA genotype was associated with radiotherapy resistance(OR=1.76,95%CI:1.18-2.63,P=0.005).Stratified analysis showed that the association between rs4588 and rs12794714 was significant only in the subgroup with higher 25(OH)D levels.CONCLUSION GC and CYP2R1 genes polymorphisms are associated with NPC susceptibility and radiotherapy response,and this association may be affected by serum 25(OH)D levels.This study provides a new idea for the prevention and individualized treatment in NPC.展开更多
According to the International Cancer Research Institute of the World Health Organization data,nasopharyngeal carcinoma(NPC)remains a significant health concern,particularly in regions such as Southeast Asia and south...According to the International Cancer Research Institute of the World Health Organization data,nasopharyngeal carcinoma(NPC)remains a significant health concern,particularly in regions such as Southeast Asia and southern China.Recently,substantial progress has been made in the field of basic and translational research on NPC,enhancing our understanding of the molecular mechanisms underlying the disease and paving the way for precise therapeutic approaches.This review summarizes the advances in NPC research,focusing on key areas that include radiotherapy and chemotherapy resistance and tumor metastasis,microenvironment,metabolism,microbiome,and biomarkers.Additionally,future research directions in NPC are discussed to provide valuable insights to advance the field further.展开更多
Accurate cancer staging is the foundation of precision oncology and guides prognosis prediction and therapeutic decision-making. The conjoint TNM System by the American Joint Committee on Cancer (AJCC) and the Interna...Accurate cancer staging is the foundation of precision oncology and guides prognosis prediction and therapeutic decision-making. The conjoint TNM System by the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC) has served as the global standard for tumor classification since inception.展开更多
Objective Histamine N-methyltransferase(HNMT)is involved primarily in histamine metabolism,but emerging evidence suggests its potential role in cancer progression.This study investigated the role of HNMT in nasopharyn...Objective Histamine N-methyltransferase(HNMT)is involved primarily in histamine metabolism,but emerging evidence suggests its potential role in cancer progression.This study investigated the role of HNMT in nasopharyngeal carcinoma(NPC)and its impact on interferon(IFN)signaling,thioredoxin-interacting protein(TXNIP),and p53 tumor suppressor pathways.Methods HNMT expression in NPC tissues and cell lines was analyzed via qPCR and Western blotting.Functional assays,including cell proliferation,migration,invasion,and apoptosis,were performed after HNMT knockdown or overexpression.Transcriptomic sequencing was used to identify differentially expressed genes(DEGs).In addition,we examined the relationship between HNMT and the IFN/TXNIP/p53 axis via rescue experiments in vitro and in vivo models via qPCR and Western blotting.Results HNMT knockdown reduced cell proliferation,migration,and invasion,and promoted apoptosis in NPC tissues and cell lines.TXNIP was the most significantly upregulated gene following HNMT knockdown.Inhibition of the IFN pathway reversed these effects,confirming the role of HNMT in downregulating the IFN/TXNIP/p53 pathway.An in vivo study revealed that HNMT overexpression correlated with reduced expression of TXNIP and p53 in NCG mice.Conclusion In NPC,HNMT promotes tumor growth and progression by inhibiting the IFN/TXNIP/p53 axis.These findings suggest that targeting the HNMT axis or restoring its function could provide new therapeutic strategies for NPC.展开更多
BACKGROUND Circulating tumor DNA(ctDNA)-based liquid biopsy has been found to be effective for the detection of minimal residual disease and the evaluation of prognostic risk in various solid tumors,with good sensitiv...BACKGROUND Circulating tumor DNA(ctDNA)-based liquid biopsy has been found to be effective for the detection of minimal residual disease and the evaluation of prognostic risk in various solid tumors,with good sensitivity and specificity for identifying patients at high risk of recurrence.However,use of its results as a biomarker for guiding the treatment and predicting the prognosis of naso-pharyngeal carcinoma(NPC)has not been reported.CASE SUMMARY In this case study of a patient with stage IVb NPC,we utilized ctDNA as an independent biomarker to guide treatment.Chemotherapy was administered in the early stages of the disease,and local intensity-modulated radiation therapy was added when the patient tested positive for ctDNA,while radiation therapy was stopped and the patient was observed when the ctDNA test was negative.During the follow-up period,ctDNA signals became positive before tumor progression and became negative again at the end of treatment.We also explored the potential of ctDNA in combination with Epstein-Barr virus(EBV)DNA status to predict the prognosis of NPC patients,as well as the criteria for selecting genetic mutations and the testing cycle for ctDNA analysis.CONCLUSION The results of ctDNA-based liquid biopsy can serve as an independent biomarker,either independently or in conjunction with EBV DNA status,to guide the treatment and predict the prognosis of NPC.展开更多
It is hereby declared that the article entitled“miR-34c-3p Inhibits Nasopharyngeal Carcinoma Development via Inhibiting M2 Polarization of Macrophages”(Yuzi Ji,Yujie Wang,Jiqing Ma,Zhihua Yin,Fei Liu,Yanzi Zang,Guan...It is hereby declared that the article entitled“miR-34c-3p Inhibits Nasopharyngeal Carcinoma Development via Inhibiting M2 Polarization of Macrophages”(Yuzi Ji,Yujie Wang,Jiqing Ma,Zhihua Yin,Fei Liu,Yanzi Zang,Guangke Wang,and Yong Tai),published in Biomedical and Environmental Sciences February 2025,Volume 38(2),Page 219-229.展开更多
Objective miR-34c-3p is down-regulated in nasopharyngeal carcinoma(NPC).The biological role of miR-34c-3p in NPC and its underlying mechanisms are unknown and were explored in this study.Methods Flow cytometry and imm...Objective miR-34c-3p is down-regulated in nasopharyngeal carcinoma(NPC).The biological role of miR-34c-3p in NPC and its underlying mechanisms are unknown and were explored in this study.Methods Flow cytometry and immunohistochemical staining were employed to detect cluster of differentiation 86(CD86)and cluster of differentiation 206(CD206)expression;quantitative real-time polymerase chain reaction(qRT-PCR)and western blotting were employed to examine mRNA expression and protein levels;cell counting kit-8(CCK8)and transwell assays were employed to assess cell proliferation,migration,and invasion;and hematoxylin-eosin(HE)staining was employed to assess pathological changes in tumor tissues.Results Our results revealed that the miR-34c-3p mimic markedly inhibited M2 polarization of macrophages by targeting SLC7A11,and M2 macrophages transfected with the miR-34c-3p mimic inhibited the proliferation,migration,and invasion of NPC cells.The in vivo experiments further confirmed that miR-34c-3p mimics blocked tumor growth and reduced inflammatory infiltration in tumor tissues.Conclusion This study provides novel insights into the pathogenesis of NPC and a new treatment strategy.展开更多
基金financially supported by National Natural Science Foundation ofChina(No.12374405)Provincial Science Foundation for Distinguished Young Scholars of Fujian(No.2024J010024)+1 种基金Natural Science Foundation of Fujian Province of China(No.2023J011267)Major Research Projects for Young and Middle-aged Researchers of Fujian Provincial Health Commission(No.2021ZQNZD010).
文摘Nasopharyngeal carcinoma(NPC)is a malignant tumor prevalent in southern China and Southeast Asia,where its early detection is crucial for improving patient prognosis and reducing mortality rates.However,existing screening methods suffer from limitations in accuracy and accessibility,hindering their application in large-scale population screening.In this work,a surface-enhanced Raman spectroscopy(SERS)-based method was established to explore the profiles of different stratified components in saliva from NPC and healthy subjects after fractionation processing.The study findings indicate that all fractionated samples exhibit diseaseassociated molecular signaling differences,where small-molecule(molecular weight cut-offvalue is 10 kDa)demonstrating superior classification capabilities with sensitivity of 90.5%and speci-ficity of 75.6%,area under receiver operating characteristic(ROC)curve of 0:925±0:031.The primary objective of this study was to qualitatively explore patterns in saliva composition across groups.The proposed SERS detection strategy for fractionated saliva offers novel insights for enhancing the sensitivity and reliability of noninvasive NPC screening,laying the foundation for translational application in large-scale clinical settings.
基金Supported by The Suzhou Medical Center,No.Szlcyxzx202103The National Natural Science Foundation of China,No.82171828+15 种基金The Key R and D Plan of Jiangsu Province(Development of Social),No.BE2021652The Subject Construction Support Project of The Second Affiliated Hospital of Soochow University,No.XKTJHRC20210011The Wu Jieping Medical Foundation,No.320.6750.2021-01-12The Special Project of"Technological Innovation"Project of CNNC Medical Industry Co.Ltd,No.ZHYLTD2021001The Suzhou Science and Education Health Project,No.KJXW2021018Foundation of Chinese Society of Clinical Oncology,No.Y-pierrefabre202102-0113 and No.Y-XD202002/zb-0015The Beijing Bethune Charitable Foundation,No.STLKY0016The Research Projects of China Baoyuan Investment Co.Ltd,No.270004The Suzhou Gusu Health Talent Program,No.GSWS2022028The Open Project of State Key Laboratory of Radiation Medicine and Protection of Soochow University,No.GZN1202302The New Medical Technology Project of the Second Affiliated Hospital of Soochow University,No.23zl001The Multi-center Clinical Research Project for Major Diseases in Suzhou,No.DZXYJ202304The Postgraduate Research and Practice Innovation Program of Jiangsu Province,No.SJCX24_1814The Gusu Health Talent Research Fund,No.GSWS2022053The National Natural Science Foundation of China,No.82102824The Scientific Research Program for Young Talents of China National Nuclear Corporation。
文摘BACKGROUND Bone is a major site of metastasis in nasopharyngeal carcinoma(NPC).Recently,nuclear factor kappa-beta ligand(RANKL)inhibitors have garnered attention for their ability to inhibit osteoclast formation and bone resorption,as well as their potential to modulate immune functions and thereby enhance the efficacy of programmed cell death protein 1(PD-1)inhibitor therapy.CASE SUMMARY We present a case of a patient with NPC who developed sternal stalk metastasis and multiple bone metastases with soft tissue invasion following radical chemoradiotherapy and targeted therapy.Prior to chemotherapy,the patient experienced severe bone marrow suppression and opted out of further chemotherapy sessions.However,the patient received combination therapy,including RANKL inhibitors(denosumab)alongside PD-1,radiotherapy,and granulocyte-macrophage colonystimulating factor(PRaG)therapy(NCT05435768),and achieved 16 months of progression-free survival and more than 35 months of overall survival,without encountering any grade 2 or higher treatment-related adverse events.CONCLUSION Denosumab combined with PRaG therapy could be a new therapeutic approach for the second-line treatment in patients with bone metastases.
基金supported by the Project of Administration of Traditional Chinese Medicine of Guangxi Zhuang Autonomous Region(grant number GZSY22-69)the Middle/Young aged Teachers’Research Ability Improvement Project of Guangxi Higher Education(grant number 2024KY0120).
文摘Objective:To investigate the chemical components of Semen podocarpi extract(SPE)and its effect on nasopharyngeal carcinoma cells and CNE-2R cells.Methods:Chemical components in SPE were identified by UPLC-MS/MS.CCK-8 and cell cloning experiments were applied to evaluate the effects of SPE on the proliferation of CNE-2R cells,and a single-hit multitarget model was used to calculate the radiobiological parameters.Cell apoptosis and cell cycle were analyzed by flow cytometry,and the levels of genes and proteins of the Raf/MEK/ERK pathway were determined by RT-PCR and Western blotting.Results:A total of 37 compounds from SPE were identified,and SPE with or without irradiation inhibited the proliferation of CNE-2R cells.SPE also promoted apoptosis,arrested cells in the G_(2)/M phase,and presented radiosensitizing effects.Compared with irradiation alone,the effects of SPE+irradiation on apoptosis and cell cycle distribution were not significantly different.In addition,SPE had no significant effect on MEK gene expression.SPE significantly increased the gene expression of C-Raf and significantly reduced the protein expression of C-Raf,as well as the gene and protein expression of ERK1 and ERK2.The protein levels of C-Raf,ERK1,and ERK2 were also significantly lower in cells treated with SPE+irradiation than in cells treated with irradiation alone.Conclusions:The effects of SPE on inhibiting cell proliferation and promoting apoptosis are likely associated with cell cycle arrest and Raf/MEK/ERK pathway regulation,and the mechanism underlying radiosensitization by SPE may involve downregulating the protein expression of C-Raf,ERK1,and ERK2.
基金supported by the National Natural Science Foundation of China(No.61975031)Fujian Provincial Health Technology Project(Grant number:2021GGA004)the Natural Science Foundation of Fujian Province(Grant number:2020J011104).
文摘Filopodia function as cellular sensors,detecting the microenvironment and directing cell migration.They play a crucial role in cancer metastasis.Quantifying the filopodia characteristics of cancer cells is a prerequisite for studying the complex role of filopodia in cancer cell metastasis.Several algorithms have been developed,yet most of these algorithms are typically suited for extracting filopodia from individual cells.This paper aims to develop an independent algorithm(MC-FiloAssay)for quantifying filopodia in multi-cell environments.The filopodia of nasopharyngeal carcinoma cells(CNE2 and 5-8F)and normal nasopharyngeal epithelial cells(NP69)were quantified with MC-FiloAssay.A linear regression analysis comparing filopodia lengths measured by MC-FiloAssay and manual annotation yielded a coefficient of determination(R^(2)=0.99),indicating high accuracy in multi-cell filopodia extraction.Furthermore,MC-FiloAssay outperforms existing algorithms under low signal conditions and in multi-cell fields of view.Analysis of CNE2 cells at different confluences revealed that confluence does not affect filopodia length or width but influences filopodia density.Additionally,significant differences were observed between CNE2 and the other two cell lines(5-8 F and NP69):CNE2 filopodia were longer,thinner,and more densely distributed.These results demonstrate that MCFiloAssay is a robust tool for multi-cell filopodia quantification.
基金supported by the National Natural Science Foundation(82261160657,82102490,and 81572781)the Guangdong Basic and Applied Basic Research Foundation(2024A1515013061)+2 种基金the Sci-Tech Project Foundation of Guangzhou City(2023A04J2141)Chang Jiang Scholars Program(J.-X.B.)the Hong Kong Research Grant Council(RGC)Theme-based Research Scheme Funds(T12-703/22-R and T12-703/23-N).
文摘Various genetic association studies have identified numerous single nucleotide polymorphisms(SNPs)associated with nasopharyngeal carcinoma(NPC)risk.However,these studies have predominantly focused on common variants,leaving the contribution of rare variants to the“missing heritability”largely unexplored.Here,we integrate genotyping data from 3925 NPC cases and 15,048 healthy controls to identify a rare SNP,rs141121474,resulting in a Glu510Lys mutation in KLHDC4 gene linked to increased NPC risk.Subsequent analyses reveal that KLHDC4 is highly expressed in NPC and correlates with poorer prognosis.Functional characterizations demonstrate that KLHDC4 acts as an oncogene in NPC cells,enhancing their migratory and metastatic capabilities,with these effects being further augmented by the Glu510Lys mutation.Mechanistically,the Glu510Lys mutant exhibits increased interaction with Vimentin compared to the wild-type KLHDC4(KLHDC4-WT),leading to elevated Vimentin protein stability and modulation of the epithelial-mesenchymal transition process,thereby promoting tumor metastasis.Moreover,Vimentin knockdown significantly mitigates the oncogenic effects induced by overexpression of both KLHDC4-WT and the Glu510Lys variant.Collectively,our findings highlight the critical role of the rare KLHDC4 variant rs141121474 in NPC progression and propose its potential as a diagnostic and therapeutic target for NPC patients.
文摘Objective:Radiotherapy(RT)is the definitive treatment for stageⅡnasopharyngeal carcinoma(NPC),which is classified as stagesⅠA andⅠB in the latest ninth edition of American Joint Committee on Cancer(AJCC)/Union for International Cancer Control(UICC).A crucial question is whether concurrent chemo-radiotherapy(CCRT)could derive additional benefits to this recent“down-staging”subgroup of NPC patients.This study aimed to interrogate clinical and radiomic features for predicting 5-year progression-free survival(PFS)of stageⅡNPC treated with RT alone or CCRT.Methods:Imaging and clinical data of 166 stageⅡNPC(eighth edition AJCC/UICC)patients were collected.Data were allocated into training,internal testing,and external testing sets.For each case,851 radiomic features were extracted and 10 clinical features were collected.Radiomic and clinical features most associated with the 5-year PFS were selected separately.A combined model was developed using multivariate logistic regression by integrating selected features and treatment option to predict 5-year PFS.Model performances were evaluated by area under the receiver operating curve(AUC),prediction accuracy,and decision curve analysis.Survival analyses including Kaplan-Meier analysis and Cox regression model were performed for further analysis.Results:Thirteen radiomic features,three clinical features,and treatment option were considered for model development.The combined model showed higher prognostic performance than using either.For the merged testing set(internal and external testing sets),AUC is 0.76(combined)vs.0.56-0.80(clinical or radiomic alone)and accuracy is 0.75(combined)vs.0.62-0.73(clinical or radiomic alone).Kaplan-Meier analysis using the combined model showed significant discrimination in PFS of the predicted low-risk and high-risk groups in the training and internal testing cohorts(P<0.05).Conclusions:Integrating with clinical and radiomic features could provide prognostic information on 5-year PFS under either treatment regimen,guiding individualized decisions of chemotherapy based on the predicted treatment outcome.
文摘BACKGROUND Nasopharyngeal carcinoma(NPC),exhibiting high incidence in southern China,is linked to genetic and environmental factors.Vitamin D metabolism,involving transport[group-specific component(GC)protein]and activation[25-hydroxylase(CYP2R1)enzyme],may influence NPC susceptibility and radiotherapy response.Polymorphisms in GC and CYP2R1 genes affect protein function and serum 25-hydroxyvitamin D[25(OH)D]levels,and are implicated in other cancers.However,their role in NPC-particularly in high-risk Han Chinese populations-and interaction with vitamin D status remains unclear.This case control study(360 NPC patients,550 controls)investigates these relationships to inform prevention and personalized therapy.AIM To investigate the association between vitamin D binding protein(GC)and CYP2R1 gene polymorphisms with susceptibility to NPC and radiotherapy response.METHODS A case control study design was adopted,and 360 patients with NPC and 550 healthy controls were included.TaqMan method was used to perform genotyping on GC gene loci rs4588,rs7041,and CYP2R1 gene loci rs10741657,rs12794714.Serum 25(OH)D levels were detected,and the relationship between gene polymorphisms and NPC risk and radiotherapy response was analyzed.RESULTS The GC gene rs4588 TT genotype was significantly associated with the risk of NPC in both the codominant model[odds ratio(OR)=1.68,95%CI:1.15-2.45,P=0.007]and the recessive model(OR=1.56,95%CI:1.02-2.38,P=0.039).The association between the rs4588 TT genotype and the risk of NPC was more significant in the male subgroup(OR=1.87,95%CI:1.11-3.15,P=0.019)and the squamous cell carcinoma subgroup(OR=1.89,95%CI:1.19-3.00,P=0.007).The serum 25(OH)D level of the rs7041 AA genotype carriers was significantly lower than that of the CC genotype(P<0.001).The CYP2R1 gene rs10741657 AA genotype was associated with higher serum 25(OH)D levels(P=0.003).The rs12794714 AA genotype was associated with radiotherapy resistance(OR=1.76,95%CI:1.18-2.63,P=0.005).Stratified analysis showed that the association between rs4588 and rs12794714 was significant only in the subgroup with higher 25(OH)D levels.CONCLUSION GC and CYP2R1 genes polymorphisms are associated with NPC susceptibility and radiotherapy response,and this association may be affected by serum 25(OH)D levels.This study provides a new idea for the prevention and individualized treatment in NPC.
基金supported by the National Natural Science Foundation of China(no.81930072 and no.82172870 to J.Ma)by the Key-Area Research and Development Program of Guangdong Province(no.2019B020230002 to J.Ma).
文摘According to the International Cancer Research Institute of the World Health Organization data,nasopharyngeal carcinoma(NPC)remains a significant health concern,particularly in regions such as Southeast Asia and southern China.Recently,substantial progress has been made in the field of basic and translational research on NPC,enhancing our understanding of the molecular mechanisms underlying the disease and paving the way for precise therapeutic approaches.This review summarizes the advances in NPC research,focusing on key areas that include radiotherapy and chemotherapy resistance and tumor metastasis,microenvironment,metabolism,microbiome,and biomarkers.Additionally,future research directions in NPC are discussed to provide valuable insights to advance the field further.
基金supported by the Sanming Project of Medicine in Shenzhen (SZSM202211017)。
文摘Accurate cancer staging is the foundation of precision oncology and guides prognosis prediction and therapeutic decision-making. The conjoint TNM System by the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC) has served as the global standard for tumor classification since inception.
基金supported by grants from Science Research Foundation of Yunnan Education Bureau(No.2023Y0631)Yunnan Provincial Science and Technology Project(No.202303AP140005).
文摘Objective Histamine N-methyltransferase(HNMT)is involved primarily in histamine metabolism,but emerging evidence suggests its potential role in cancer progression.This study investigated the role of HNMT in nasopharyngeal carcinoma(NPC)and its impact on interferon(IFN)signaling,thioredoxin-interacting protein(TXNIP),and p53 tumor suppressor pathways.Methods HNMT expression in NPC tissues and cell lines was analyzed via qPCR and Western blotting.Functional assays,including cell proliferation,migration,invasion,and apoptosis,were performed after HNMT knockdown or overexpression.Transcriptomic sequencing was used to identify differentially expressed genes(DEGs).In addition,we examined the relationship between HNMT and the IFN/TXNIP/p53 axis via rescue experiments in vitro and in vivo models via qPCR and Western blotting.Results HNMT knockdown reduced cell proliferation,migration,and invasion,and promoted apoptosis in NPC tissues and cell lines.TXNIP was the most significantly upregulated gene following HNMT knockdown.Inhibition of the IFN pathway reversed these effects,confirming the role of HNMT in downregulating the IFN/TXNIP/p53 pathway.An in vivo study revealed that HNMT overexpression correlated with reduced expression of TXNIP and p53 in NCG mice.Conclusion In NPC,HNMT promotes tumor growth and progression by inhibiting the IFN/TXNIP/p53 axis.These findings suggest that targeting the HNMT axis or restoring its function could provide new therapeutic strategies for NPC.
基金Supported by Beijing Bethune Charitable Foundation and Provincial Natural Science Foundation of Liaoning,No.2022-MS-190.
文摘BACKGROUND Circulating tumor DNA(ctDNA)-based liquid biopsy has been found to be effective for the detection of minimal residual disease and the evaluation of prognostic risk in various solid tumors,with good sensitivity and specificity for identifying patients at high risk of recurrence.However,use of its results as a biomarker for guiding the treatment and predicting the prognosis of naso-pharyngeal carcinoma(NPC)has not been reported.CASE SUMMARY In this case study of a patient with stage IVb NPC,we utilized ctDNA as an independent biomarker to guide treatment.Chemotherapy was administered in the early stages of the disease,and local intensity-modulated radiation therapy was added when the patient tested positive for ctDNA,while radiation therapy was stopped and the patient was observed when the ctDNA test was negative.During the follow-up period,ctDNA signals became positive before tumor progression and became negative again at the end of treatment.We also explored the potential of ctDNA in combination with Epstein-Barr virus(EBV)DNA status to predict the prognosis of NPC patients,as well as the criteria for selecting genetic mutations and the testing cycle for ctDNA analysis.CONCLUSION The results of ctDNA-based liquid biopsy can serve as an independent biomarker,either independently or in conjunction with EBV DNA status,to guide the treatment and predict the prognosis of NPC.
文摘It is hereby declared that the article entitled“miR-34c-3p Inhibits Nasopharyngeal Carcinoma Development via Inhibiting M2 Polarization of Macrophages”(Yuzi Ji,Yujie Wang,Jiqing Ma,Zhihua Yin,Fei Liu,Yanzi Zang,Guangke Wang,and Yong Tai),published in Biomedical and Environmental Sciences February 2025,Volume 38(2),Page 219-229.
文摘Objective miR-34c-3p is down-regulated in nasopharyngeal carcinoma(NPC).The biological role of miR-34c-3p in NPC and its underlying mechanisms are unknown and were explored in this study.Methods Flow cytometry and immunohistochemical staining were employed to detect cluster of differentiation 86(CD86)and cluster of differentiation 206(CD206)expression;quantitative real-time polymerase chain reaction(qRT-PCR)and western blotting were employed to examine mRNA expression and protein levels;cell counting kit-8(CCK8)and transwell assays were employed to assess cell proliferation,migration,and invasion;and hematoxylin-eosin(HE)staining was employed to assess pathological changes in tumor tissues.Results Our results revealed that the miR-34c-3p mimic markedly inhibited M2 polarization of macrophages by targeting SLC7A11,and M2 macrophages transfected with the miR-34c-3p mimic inhibited the proliferation,migration,and invasion of NPC cells.The in vivo experiments further confirmed that miR-34c-3p mimics blocked tumor growth and reduced inflammatory infiltration in tumor tissues.Conclusion This study provides novel insights into the pathogenesis of NPC and a new treatment strategy.
