Abstract
Prognostic signatures have been proposed as clinical tools to estimate prognosis in hepatocellular carcinoma (HCC), which is the second most common contributor to cancer-related death at present globally. Autophagy-related genes play a dynamic and fundamental role in HCC, but knowledge of their utility as prognostic markers is limited. Here, we facilitated univariate and multivariate Cox proportional hazards regression analyses to reveal that 3 autophagy-related genes (BIRC5, FOXO1 and SQSTM1) were closely related to the survival of HCC. Then, we generated a prognosis index (PI) for predicting overall survival (OS) based on the three genes, which was an independent prognostic indicator for the OS of HCC (HR = 1.930, 95% CI: 1.200–3.104, P = 0.007). The PI showed moderate performance for predicting the survival of HCC patients and its efficacy was validated by data from three microarrays (GSE10143, GSE10186 and GSE17856). Furthermore, we deeply mined the integrated large-scale datasets from public microarrays and immunohistochemistry to validate the overexpression of BIRC5 and SQSTM1 while down-regulated FOXO1 expression in HCC. Bioinformatic analysis offered the hypothesis that proliferative signals in high-risk HCC patients were disturbing and thereby facilitated inferior clinical outcomes. Collectively, the prognostic signature we proposed is a promising biomarker for monitoring outcome of HCC. Nevertheless, prospective experimental studies are needed to validate the clinical utility.
Highlights
Hepatocellular carcinoma (HCC), the predominant primary tumor of the liver, is the second most common contributor to cancer-related death at present globally [1,2,3]
A total of 234 genes involved directly or indirectly in autophagy were downloaded via the online database Human Autophagy Database (HADb)
After extracting expression data of these 234 autophagy-related genes from The Cancer Genome Atlas (TCGA), 33 differentially expressed genes in hepatocellular carcinoma (HCC) were identified (Figures 1 and 2), which were used for further investigation on their prognostic value
Summary
Hepatocellular carcinoma (HCC), the predominant primary tumor of the liver, is the second most common contributor to cancer-related death at present globally [1,2,3]. The considerably high mortality rate of liver tumor seriously threatens humanity, where 40,710 of the estimated new liver cancer cases in the United States in 2017 [4]. Surgical resection technology or transplantation rapidly improved, the 5-year survival rate of HCC patients remains relatively low [5, 6]. The dismal clinical outcome of HCC is in part driven by the delay in diagnosis and the still-rudimentary prognosis monitoring [7]. Extensive analyses for identifying reliable biomarkers with prognostic significance that target major oncogenes in HCC is imperative Hepatocarcinogenesis is heterogeneous and contains a multi-step process, including genetic and epigenetic factors that forms its unique molecular fingerprint.
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