Abstract
Purpose Autophagy is a lysosomal degradation pathway that is essential for maintaining the homeostasis of the intracellular environment. Mounting evidence indicates that autophagy plays an essential role in the occurrence and development of hepatocellular cancer (HCC). This research is aimed at exploring the prognostic value of autophagy-related genes (ARGs) in HCC patients. Methods The Wilcoxon test was used to identify differentially expressed ARGs in The Cancer Genome Atlas (TCGA) HCC cohort. Then, the TCGA cohort was randomly divided into training and testing groups. Cox and LASSO regression models were used to screen for autophagy-related genes that affect overall survival (OS) in the TCGA training group. Based on the coefficient of risk genes, we constructed an autophagy-related gene signature for predicting the prognosis of HCC patients. Finally, we validated the prognostic significance of autophagy-related gene signature using the TCGA testing group and three external datasets. Results ATG10, BIRC5, GAPDH, and TMEM74 are risk genes for OS. According to the optimal cutoff value of risk score in each HCC dataset, HCC patients can divide into high- and low-risk groups. ARG risk score can significantly distinguish HCC patients with different survival outcomes. Meanwhile, the ARG risk score is independently correlated with OS in multiple HCC cohorts. Conclusions The autophagy-related risk score can effectively screen high-risk HCC patients and provide guidance for clinical prevention and treatment of HCC.
Highlights
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death in China and the fourth leading cause of cancer-related death in the world
There were no significant differences in age, gender, AJCC staging, differentiation, survival status, and survival time between the
The LASSO regression and multivariate regression analysis were utilized for further screening, and we found that ATG10, BIRC5, GAPDH, and TMEM74 are risk autophagy-related genes (ARGs) for overall survival (OS)
Summary
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death in China and the fourth leading cause of cancer-related death in the world. Despite significant advances in the diagnosis and treatment of HCC in recent years, the prognosis of hepatocellular carcinoma is still poor, owing to its high invasiveness [1, 2]. It is essential to explore the molecular mechanism of the occurrence and development of liver cancer, as it can lead to a new treatment strategy for the prevention and treatment of hepatocellular carcinoma. Changes in the level of autophagy are associated with a variety of human diseases, such as cancer, autoimmune diseases, and central nervous system diseases [3,4,5,6]. Several studies have shown that autophagy can inhibit the BioMed Research International
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