期刊
WORLD JOURNAL OF GASTROENTEROLOGY
卷 25, 期 14, 页码 1715-1728出版社
BAISHIDENG PUBLISHING GROUP INC
DOI: 10.3748/wjg.v25.i14.1715
关键词
Senescence-associated genes; Hepatocellular carcinoma; Overall survival; Risk model; Asian patients
资金
- National Natural Science Foundation of China [81773128, 81871998]
- Natural Science Basic Research Plan in Shaanxi Province of China [2018JM7013, 2017JM8039]
- Research Fund for Young Star of Science and Technology in Shaanxi Province [2018KJXX-022]
- China Postdoctoral Science Foundation [2018M641000]
BACKGROUND Cellular senescence is a recognized barrier for progression of chronic liver diseases to hepatocellular carcinoma (HCC). The expression of a cluster of genes is altered in response to environmental factors during senescence. However, it is questionable whether these genes could serve as biomarkers for HCC patients. AIM To develop a signature of senescence-associated genes (SAGs) that predicts patients' overall survival (OS) to improve prognosis prediction of HCC. METHODS SAGs were identified using two senescent cell models. Univariate COX regression analysis was performed to screen the candidate genes significantly associated with OS of HCC in a discovery cohort (GSE14520) for the least absolute shrinkage and selection operator modelling. Prognostic value of this seven-gene signature was evaluated using two independent cohorts retrieved from the GEO (GSE14520) and the Cancer Genome Atlas datasets, respectively. Time-dependent receiver operating characteristic (ROC) curve analysis was conducted to compare the predictive accuracy of the seven-SAG signature and serum alpha-fetoprotein (AFP). RESULTS A total of 42 SAGs were screened and seven of them, including KIF18B, CEP55, CIT, MCM7, CDC45, EZH2, and MCM5, were used to construct a prognostic formula. All seven genes were significantly downregulated in senescent cells and upregulated in HCC tissues. Survival analysis indicated that our seven-SAG signature was strongly associated with OS, especially in Asian populations, both in discovery and validation cohorts. Moreover, time-dependent ROC curve analysis suggested the seven-gene signature had a better predictive accuracy than serum AFP in predicting HCC patients' 1-, 3-, and 5-year OS. CONCLUSION We developed a seven-SAG signature, which could predict OS of Asian HCC patients. This risk model provides new clinical evidence for the accurate diagnosis and targeted treatment of HCC.
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