Background:Hepatocellular carcinoma(HCC)is a major health problem and a primary cause of cancer-related death worldwide.Although great advances have achieved recently by large-scale high-throughput analysis,the precis...Background:Hepatocellular carcinoma(HCC)is a major health problem and a primary cause of cancer-related death worldwide.Although great advances have achieved recently by large-scale high-throughput analysis,the precise molecular mechanism underlying HCC progression remains to be clearly elucidated.We investigated the relationship between Tescalcin(TESC),a candidate oncogene,and clinicopathological features of HCC patients and explored the role of TECS in HCC development.Methods:To identify new genes involved in HCC development,we analyzed The Cancer Genome Atlas liver cancer database,and TESC was selected for further investigation.HCC tissue microarray analysis for TESC and its association with clinicopathological features were performed to investigate its clinical significance.TESC was knocked down by using short-hairpin RNAs.Cell proliferation was analyzed by WST-1 assay and cell counting.Cell apoptosis was tested by fluorescence-activated cell sorting.A subcutaneous xenograft tumor model in nude mice was established to determine the in vivo function of TESC.Affymetrix microarray was used to identify its molecular mechanism.Results:TESC was significantly increased in HCC tissues compared with the adjacent normal liver tissues.High expression of TESC was detected in 61 of 172 HCC patients by tissue microarray.Large tumor(>5 cm)and elevated total bilirubin were associated with high TESC expression(both P<0.050).In multivariate analysis,TESC was identified as an independent prognostic factor for short overall survival of HCC patients.TESC knockdown impaired HCC cell growth in vitro and in vivo.TESC knockdown significantly increased cell apoptosis in HCC cell lines.Furthermore,Affymetrix microarray analysis revealed that TESC knockdown inhibited tumor proliferation-related pathways while activated cell death-related pathways.Conclusion:TESC was identified as an independent prognostic factor for short overall survival of HCC patients,and was critical for HCC cell proliferation and survival.展开更多
基金supported by grants from the National Natural Science Foundation of China(81602143)Sun Yatsen University Cancer Center Physician-scientist Funding(16zxqk04)+3 种基金Guangdong Key Laboratory of Liver Disease Research(GS2017011002)National Science and Technology Major Project of China(2018ZX10302205,2018ZX10723204)National Natural Science Foundation of Guangdong(2017A030313605)Guangdong Province Medical Science and Technology Research Foundation(B2019132).
文摘Background:Hepatocellular carcinoma(HCC)is a major health problem and a primary cause of cancer-related death worldwide.Although great advances have achieved recently by large-scale high-throughput analysis,the precise molecular mechanism underlying HCC progression remains to be clearly elucidated.We investigated the relationship between Tescalcin(TESC),a candidate oncogene,and clinicopathological features of HCC patients and explored the role of TECS in HCC development.Methods:To identify new genes involved in HCC development,we analyzed The Cancer Genome Atlas liver cancer database,and TESC was selected for further investigation.HCC tissue microarray analysis for TESC and its association with clinicopathological features were performed to investigate its clinical significance.TESC was knocked down by using short-hairpin RNAs.Cell proliferation was analyzed by WST-1 assay and cell counting.Cell apoptosis was tested by fluorescence-activated cell sorting.A subcutaneous xenograft tumor model in nude mice was established to determine the in vivo function of TESC.Affymetrix microarray was used to identify its molecular mechanism.Results:TESC was significantly increased in HCC tissues compared with the adjacent normal liver tissues.High expression of TESC was detected in 61 of 172 HCC patients by tissue microarray.Large tumor(>5 cm)and elevated total bilirubin were associated with high TESC expression(both P<0.050).In multivariate analysis,TESC was identified as an independent prognostic factor for short overall survival of HCC patients.TESC knockdown impaired HCC cell growth in vitro and in vivo.TESC knockdown significantly increased cell apoptosis in HCC cell lines.Furthermore,Affymetrix microarray analysis revealed that TESC knockdown inhibited tumor proliferation-related pathways while activated cell death-related pathways.Conclusion:TESC was identified as an independent prognostic factor for short overall survival of HCC patients,and was critical for HCC cell proliferation and survival.
