BACKGROUND Investigating molecular biomarkers that accurately predict prognosis is of considerable clinical significance.Accumulating evidence suggests that long noncoding ribonucleic acids(lncRNAs)are frequently aber...BACKGROUND Investigating molecular biomarkers that accurately predict prognosis is of considerable clinical significance.Accumulating evidence suggests that long noncoding ribonucleic acids(lncRNAs)are frequently aberrantly expressed in colorectal cancer(CRC).AIM To elucidate the prognostic function of multiple lncRNAs serving as biomarkers in CRC.METHODS We performed lncRNA expression profiling using the lncRNA mining approach in large CRC cohorts from The Cancer Genome Atlas(TCGA)database.Receiver operating characteristic analysis was performed to identify the optimal cutoff point at which patients could be classified into the high-risk or low-risk groups.Based on the Cox coefficient of the individual lncRNAs,we identified a ninelncRNA signature that was associated with the survival of CRC patients in the training set(n=175).The prognostic value of this nine-lncRNA signature was validated in the testing set(n=174)and TCGA set(n=349).The prognostic models,consisting of these nine CRC-specific lncRNAs,performed well for risk stratification in the testing set and TCGA set.Time-dependent receiver operating characteristic analysis indicated that this predictive model had good performance.RESULTS Multivariate Cox regression and stratification analysis demonstrated that this nine-lncRNA signature was independent of other clinical features in predicting overall survival.Functional enrichment analysis of Kyoto Encyclopedia of Genes and Genomes pathways and Gene Ontology terms further indicated that these nine prognostic lncRNAs were closely associated with carcinogenesis-associated pathways and biological functions in CRC.CONCLUSION A nine-lncRNA expression signature was identified and validated that could improve the prognosis prediction of CRC,thereby providing potential prognostic biomarkers and efficient therapeutic targets for patients with CRC.展开更多
BACKGROUND Accumulating evidence has revealed that several long non-coding ribonucleic acids(lncRNAs)are crucial in the progress of hepatocellular carcinoma(HCC).AIM To classify a long non-coding RNA,i.e.,lncRNA W5,an...BACKGROUND Accumulating evidence has revealed that several long non-coding ribonucleic acids(lncRNAs)are crucial in the progress of hepatocellular carcinoma(HCC).AIM To classify a long non-coding RNA,i.e.,lncRNA W5,and to determine the clinical significance and potential roles of lncRNA W5 in HCC.METHODS The results showed that lncRNA W5 expression was significantly downregulated in HCC cell lines and tissues.Analysis of the association between lncRNA W5 expression levels and clinicopathological features suggested that low lncRNA W5 expression was related to large tumor size(P<0.01),poor histological grade(P<0.05)and serious portal vein tumor thrombosis(P<0.05).Furthermore,Kaplan-Meier survival analysis showed that low expression of lncRNA W5 predicts poor overall survival(P=0.016).RESULTS Gain-of-loss function experiments,including cell counting kit8 assays,colony formation assays,and transwell assays,were performed in vitro to investigate thebiological roles of lncRNA W5.In vitro experiments showed that ectopic overexpression of lncRNA W5 suppressed HCC cell proliferation,migration and invasion;conversely,silencing of lncRNA W5 promoted cell proliferation,migration and invasion.In addition,acting as a tumor suppressor gene in HCC,lncRNA W5 inhibited the growth of HCC xenograft tumors in vivo.CONCLUSION These results showed that lncRNA W5 is down-regulated in HCC,and it may suppress HCC progression and predict poor clinical outcomes in patients with HCC.LncRNA W5 may serve as a potential HCC prognostic biomarker in addition to a therapeutic target.展开更多
基金National Natural Science Foundation of China,No.81860433the Natural Science Youth Foundation of Jiangxi Province,No.20192BAB215036+2 种基金the Foundation for Fostering Young Scholar of Nanchang University,No.PY201822National Natural Science Foundation of China,No.81960359the Key Technology Research and Development Program of Jiangxi Province,No.20202BBG73024.
文摘BACKGROUND Investigating molecular biomarkers that accurately predict prognosis is of considerable clinical significance.Accumulating evidence suggests that long noncoding ribonucleic acids(lncRNAs)are frequently aberrantly expressed in colorectal cancer(CRC).AIM To elucidate the prognostic function of multiple lncRNAs serving as biomarkers in CRC.METHODS We performed lncRNA expression profiling using the lncRNA mining approach in large CRC cohorts from The Cancer Genome Atlas(TCGA)database.Receiver operating characteristic analysis was performed to identify the optimal cutoff point at which patients could be classified into the high-risk or low-risk groups.Based on the Cox coefficient of the individual lncRNAs,we identified a ninelncRNA signature that was associated with the survival of CRC patients in the training set(n=175).The prognostic value of this nine-lncRNA signature was validated in the testing set(n=174)and TCGA set(n=349).The prognostic models,consisting of these nine CRC-specific lncRNAs,performed well for risk stratification in the testing set and TCGA set.Time-dependent receiver operating characteristic analysis indicated that this predictive model had good performance.RESULTS Multivariate Cox regression and stratification analysis demonstrated that this nine-lncRNA signature was independent of other clinical features in predicting overall survival.Functional enrichment analysis of Kyoto Encyclopedia of Genes and Genomes pathways and Gene Ontology terms further indicated that these nine prognostic lncRNAs were closely associated with carcinogenesis-associated pathways and biological functions in CRC.CONCLUSION A nine-lncRNA expression signature was identified and validated that could improve the prognosis prediction of CRC,thereby providing potential prognostic biomarkers and efficient therapeutic targets for patients with CRC.
基金Supported by National High Technology Research and Development Program of China,No.2015AA020924Natural Science Foundation of Beijing,China,No.7202194 and No.7162185.
文摘BACKGROUND Accumulating evidence has revealed that several long non-coding ribonucleic acids(lncRNAs)are crucial in the progress of hepatocellular carcinoma(HCC).AIM To classify a long non-coding RNA,i.e.,lncRNA W5,and to determine the clinical significance and potential roles of lncRNA W5 in HCC.METHODS The results showed that lncRNA W5 expression was significantly downregulated in HCC cell lines and tissues.Analysis of the association between lncRNA W5 expression levels and clinicopathological features suggested that low lncRNA W5 expression was related to large tumor size(P<0.01),poor histological grade(P<0.05)and serious portal vein tumor thrombosis(P<0.05).Furthermore,Kaplan-Meier survival analysis showed that low expression of lncRNA W5 predicts poor overall survival(P=0.016).RESULTS Gain-of-loss function experiments,including cell counting kit8 assays,colony formation assays,and transwell assays,were performed in vitro to investigate thebiological roles of lncRNA W5.In vitro experiments showed that ectopic overexpression of lncRNA W5 suppressed HCC cell proliferation,migration and invasion;conversely,silencing of lncRNA W5 promoted cell proliferation,migration and invasion.In addition,acting as a tumor suppressor gene in HCC,lncRNA W5 inhibited the growth of HCC xenograft tumors in vivo.CONCLUSION These results showed that lncRNA W5 is down-regulated in HCC,and it may suppress HCC progression and predict poor clinical outcomes in patients with HCC.LncRNA W5 may serve as a potential HCC prognostic biomarker in addition to a therapeutic target.