Background: Insulin?like growth factor?binding protein?3(IGFBP?3) is suggested to predict the radiosensitivity and/or prognosis of patients with esophageal squamous cell carcinoma(ESCC). The present study was designed...Background: Insulin?like growth factor?binding protein?3(IGFBP?3) is suggested to predict the radiosensitivity and/or prognosis of patients with esophageal squamous cell carcinoma(ESCC). The present study was designed to investi?gate the clinical and prognostic efects of IGFBP?3 on ESCC.Methods: IGFBP?3 was detected by immunohistochemistry in parain?embedded tissues from 70 ESCC patients treated with radiotherapy alone and further examined by western blotting analysis in 10 pairs of fresh ESCC tissues and adjacent non?malignant esophageal specimens. Receiver operating characteristic(ROC) analysis was used to determine cut?of scores for tumor positivity and to evaluate patient survival status. The χ2 test was performed to analyze the association of IGFBP?3 expression with clinical characteristics and radiotherapy response. Associations between prognostic outcomes and IGFBP?3 expression were investigated using Kaplan–Meier analysis and the Cox proportional hazards model.Results: The threshold for IGFBP?3 positivity was set to greater than 65% [area under the ROC curve(AUC)(45.7%) were deined as having high IGFBP?3 expression= 0.690, P < 0.019]. Of the 70 ESCC patient tissues tested, 32. The levels of IGFBP?3 protein expression were decreased in 70.0%(7 of 10) of ESCC tissues compared with adjacent non?malignant esophageal tissue. In addition, IGFBP?3 expression was associated with pathologic classiication(P < 0.05 for T, N, and M categories and clinical stage). Patients with elevated protein level of IGFBP?3 in the tumor had an improved radiotherapy response and prolonged overall survival(P < 0.001).Conclusions: High level of IGFBP?3 expression in ESCC associates with early clinical stages and are predictive for favorable survival of the patients treated with radiotherapy.展开更多
Esophageal squamous cell carcinoma(ESCC)is among the most prevalent causes of cancer-related death in patients worldwide.Resistance to immunotherapy and chemotherapy results in worse survival outcomes in ESCC.It is ur...Esophageal squamous cell carcinoma(ESCC)is among the most prevalent causes of cancer-related death in patients worldwide.Resistance to immunotherapy and chemotherapy results in worse survival outcomes in ESCC.It is urgent to explore the underlying molecular mechanism of immune evasion and chemoresistance in ESCC.Here,we conducted RNA-sequencing analysis in ten ESCC tissues from cisplatin-based neoadjuvant chemotherapy patients.We found that DMRTA1 was extremely upregulated in the non-pathologic complete response(non-pCR)group.The proliferation rate of esophageal squamous carcinoma cells was markedly decreased after knockdown of DMRTA1 expression,which could increase cisplatin sensitivity in ESCC.Additionally,suppression of DMRTA1 could decrease the immune escape of esophageal squamous carcinoma cells.Further mechanistic studies suggest that DMRTA1 can promote its expression by binding to the promoter of SOX2,which plays important roles in the progression and chemoresistance of ESCC in the form of positive feedback.Therefore,DMRTA1 could be a potential target to suppress immune escape and overcome chemoresistance in ESCC.展开更多
Volatile organic compounds(VOCs)are carbon-based chemicals characterized by high vapor pressure and low boiling points under standard temperature and pressure conditions.VOCs are categorized as exogenous or endogenous...Volatile organic compounds(VOCs)are carbon-based chemicals characterized by high vapor pressure and low boiling points under standard temperature and pressure conditions.VOCs are categorized as exogenous or endogenous,depending on their source.Endogenous VOCs are metabolic byproducts eliminated via respiration.These compounds serve as indicators of human metabolic activity,reflecting differences in tumors compared to normal cell metabolism and the body's response to tumors.Examination of exhaled breath provides a noninvasive approach for assessing metabolic status by comparing VOC levels.Consequently,VOCs are increasingly studied as novel biomarkers for cancer screening,diagnosis,and treatment efficacy prediction.This review outlines VOC production mechanisms,their presence in tumor types,detection methodologies,and their implications for tumor screening,diagnosis,and prognosis.Nonetheless,challenges remain in the utilization of VOCs for cancer diagnosis and predicting treatment outcomes.Furthermore,this review discusses unresolved issues requiring attention to improve malignant tumor assessment,providing insights into their diagnosis,treatment,and prognosis.展开更多
Background:Blood-based cell-free DNA(cfDNA)methylation testing has emerged as a promising approach for multi-cancer early detection(MCED),holding the potential to improve cancer survival rates.However,traditional bisu...Background:Blood-based cell-free DNA(cfDNA)methylation testing has emerged as a promising approach for multi-cancer early detection(MCED),holding the potential to improve cancer survival rates.However,traditional bisulfite-based methods often encounter sensitivity limitations in detecting early-stage malignancies or certain cancer types.In the INSPECTOR study,we developed a MCED and cancer signal origin(CSO)system specifically designed for early-stage or hard-to-detect cancers,including those of the lung,breast,colorectum,liver,esophagus,stomach,pancreas,and ovary.Methods:We established a comprehensive methylation marker discovery database(n=6,342)by integrating public datasets(n=4,699)and in-house samples(n=1,643),all processed using human TET(hTET)enzyme-assisted whole-methylome sequencing(GM-seq).This enabled the design of a targeted panel encompassing 155,362 methylated CpG sites.Leveraging hTET-assisted high-depth next-generation sequencing(NGS),our blood test achieved amedian unique depth of 1,093×.Multicenter case-control cohorts,including various pathological subtypes,were used for training,validation,and independent validation of MCED and CSO models,and to verify the clinical feasibility.Results:Clinical validation was conducted across multi-center case-control cohorts,including 1,071 participants in the training set,581 in the validation set,and 824 in the independent validation set.TheMCEDassay demonstrated robust performancewith a specificity of 99.1%and sensitivity of 83.2%in the training set,99.0%and 81.8%in the validation set,and comparable results in the independent validation set(99.0%specificity,81.9%sensitivity).Notably,sensitivity reached 65.5%for stage I cancers,79.7%for stage II,and 71.3%for stages I-II combined.The sensitivities for different cancer types were as follows:esophageal(79.2%),gastric(76.1%),colorectal(86.2%),pancreatic(66.7%),liver(100.0%),lung(72.9%),breast(88.9%),and ovarian(87.9%).The CSO model exhibited strong accuracy,with top-1 cancer origin prediction rates of 87.9%(validation)and 87.4%(independent validation),rising to 95.1%and 94.5%for top-2 predictions,respectively.For stage I cancers specifically,the top-1 accuracy was 85.5%.Conclusions:These findings underscore the efficacy of the hTET-assisted cfDNA methylation sequencing system across diverse cancer types,particularly in early stages.Enzyme-assisted NGS test of methylated cfDNA thus enhances the clinical utility of non-invasive blood-based screening.展开更多
基金supported by a Grant from the National Natural Science Foundation of China (NSFC 81272487)the Foundation of Guangdong Esophageal Cancer Research Institute (M201415)
文摘Background: Insulin?like growth factor?binding protein?3(IGFBP?3) is suggested to predict the radiosensitivity and/or prognosis of patients with esophageal squamous cell carcinoma(ESCC). The present study was designed to investi?gate the clinical and prognostic efects of IGFBP?3 on ESCC.Methods: IGFBP?3 was detected by immunohistochemistry in parain?embedded tissues from 70 ESCC patients treated with radiotherapy alone and further examined by western blotting analysis in 10 pairs of fresh ESCC tissues and adjacent non?malignant esophageal specimens. Receiver operating characteristic(ROC) analysis was used to determine cut?of scores for tumor positivity and to evaluate patient survival status. The χ2 test was performed to analyze the association of IGFBP?3 expression with clinical characteristics and radiotherapy response. Associations between prognostic outcomes and IGFBP?3 expression were investigated using Kaplan–Meier analysis and the Cox proportional hazards model.Results: The threshold for IGFBP?3 positivity was set to greater than 65% [area under the ROC curve(AUC)(45.7%) were deined as having high IGFBP?3 expression= 0.690, P < 0.019]. Of the 70 ESCC patient tissues tested, 32. The levels of IGFBP?3 protein expression were decreased in 70.0%(7 of 10) of ESCC tissues compared with adjacent non?malignant esophageal tissue. In addition, IGFBP?3 expression was associated with pathologic classiication(P < 0.05 for T, N, and M categories and clinical stage). Patients with elevated protein level of IGFBP?3 in the tumor had an improved radiotherapy response and prolonged overall survival(P < 0.001).Conclusions: High level of IGFBP?3 expression in ESCC associates with early clinical stages and are predictive for favorable survival of the patients treated with radiotherapy.
基金funded by the Department of Education of Yunnan Province(No.2021J0244).
文摘Esophageal squamous cell carcinoma(ESCC)is among the most prevalent causes of cancer-related death in patients worldwide.Resistance to immunotherapy and chemotherapy results in worse survival outcomes in ESCC.It is urgent to explore the underlying molecular mechanism of immune evasion and chemoresistance in ESCC.Here,we conducted RNA-sequencing analysis in ten ESCC tissues from cisplatin-based neoadjuvant chemotherapy patients.We found that DMRTA1 was extremely upregulated in the non-pathologic complete response(non-pCR)group.The proliferation rate of esophageal squamous carcinoma cells was markedly decreased after knockdown of DMRTA1 expression,which could increase cisplatin sensitivity in ESCC.Additionally,suppression of DMRTA1 could decrease the immune escape of esophageal squamous carcinoma cells.Further mechanistic studies suggest that DMRTA1 can promote its expression by binding to the promoter of SOX2,which plays important roles in the progression and chemoresistance of ESCC in the form of positive feedback.Therefore,DMRTA1 could be a potential target to suppress immune escape and overcome chemoresistance in ESCC.
文摘Volatile organic compounds(VOCs)are carbon-based chemicals characterized by high vapor pressure and low boiling points under standard temperature and pressure conditions.VOCs are categorized as exogenous or endogenous,depending on their source.Endogenous VOCs are metabolic byproducts eliminated via respiration.These compounds serve as indicators of human metabolic activity,reflecting differences in tumors compared to normal cell metabolism and the body's response to tumors.Examination of exhaled breath provides a noninvasive approach for assessing metabolic status by comparing VOC levels.Consequently,VOCs are increasingly studied as novel biomarkers for cancer screening,diagnosis,and treatment efficacy prediction.This review outlines VOC production mechanisms,their presence in tumor types,detection methodologies,and their implications for tumor screening,diagnosis,and prognosis.Nonetheless,challenges remain in the utilization of VOCs for cancer diagnosis and predicting treatment outcomes.Furthermore,this review discusses unresolved issues requiring attention to improve malignant tumor assessment,providing insights into their diagnosis,treatment,and prognosis.
基金the Ethics Committee of the Cancer Prevention Center,Sun Yat-sen University(SL-B2023-717-01)Chinese PLA General Hospital(S2021-427-01)+2 种基金The Sixth Affiliated Hospital of Sun Yat-sen University(2024ZSLYEC-361)Gansu Provincial Cancer Hospital(IRB-PJ-2024-043)Shenzhen Bao’an District Songgang People’s Hospital(PY202408020003).
文摘Background:Blood-based cell-free DNA(cfDNA)methylation testing has emerged as a promising approach for multi-cancer early detection(MCED),holding the potential to improve cancer survival rates.However,traditional bisulfite-based methods often encounter sensitivity limitations in detecting early-stage malignancies or certain cancer types.In the INSPECTOR study,we developed a MCED and cancer signal origin(CSO)system specifically designed for early-stage or hard-to-detect cancers,including those of the lung,breast,colorectum,liver,esophagus,stomach,pancreas,and ovary.Methods:We established a comprehensive methylation marker discovery database(n=6,342)by integrating public datasets(n=4,699)and in-house samples(n=1,643),all processed using human TET(hTET)enzyme-assisted whole-methylome sequencing(GM-seq).This enabled the design of a targeted panel encompassing 155,362 methylated CpG sites.Leveraging hTET-assisted high-depth next-generation sequencing(NGS),our blood test achieved amedian unique depth of 1,093×.Multicenter case-control cohorts,including various pathological subtypes,were used for training,validation,and independent validation of MCED and CSO models,and to verify the clinical feasibility.Results:Clinical validation was conducted across multi-center case-control cohorts,including 1,071 participants in the training set,581 in the validation set,and 824 in the independent validation set.TheMCEDassay demonstrated robust performancewith a specificity of 99.1%and sensitivity of 83.2%in the training set,99.0%and 81.8%in the validation set,and comparable results in the independent validation set(99.0%specificity,81.9%sensitivity).Notably,sensitivity reached 65.5%for stage I cancers,79.7%for stage II,and 71.3%for stages I-II combined.The sensitivities for different cancer types were as follows:esophageal(79.2%),gastric(76.1%),colorectal(86.2%),pancreatic(66.7%),liver(100.0%),lung(72.9%),breast(88.9%),and ovarian(87.9%).The CSO model exhibited strong accuracy,with top-1 cancer origin prediction rates of 87.9%(validation)and 87.4%(independent validation),rising to 95.1%and 94.5%for top-2 predictions,respectively.For stage I cancers specifically,the top-1 accuracy was 85.5%.Conclusions:These findings underscore the efficacy of the hTET-assisted cfDNA methylation sequencing system across diverse cancer types,particularly in early stages.Enzyme-assisted NGS test of methylated cfDNA thus enhances the clinical utility of non-invasive blood-based screening.
