Abstract
Accumulating evidence has proved that autophagy serves as a tumor promoter in formed malignancies, and the autophagy-related prognostic signatures have been constructed as clinical tools to predict prognosis in many high-mortality cancers. Autophagy-related genes have participated in the development and metastasis of hepatocellular carcinoma (HCC), but the understanding of their prognostic value is limited. Thereafter, LIMMA and survival analysis were conducted in both ICGC and TCGA databases and a total of 10 hub autophagy-related genes, namely, NPC1, CDKN2A, RPTOR, SPHK1, HGS, BIRC5, SPNS1, BAK1, ATIC, and MAPK3, were collected. Then, GO, KEGG, correlation, consensus, and PCA analyses were utilized to reveal their potential targeted role in HCC treatment. Single-cell RNA-seq of cancer stem cells also indicated that there was a positive correlation between these genes and stemness. In parallel, we applied univariate, LASSO, and multivariate regression analyses to study the autophagy-related genes and finally proposed that ATIC and BIRC5 were the valuable prognostic indicators of HCC. The signature based on ATIC and BIRC5 exhibited moderate power for predicting the survival of HCC in the ICGC cohort, and its efficacy was further validated in the TCGA cohort. Taken together, we suggested that 10 aforementioned hub genes are promising therapeutic targets of HCC and the ATIC/BIRC5 prognostic signature is a practical prognostic indicator for HCC patients.
Highlights
As one of the most generally diagnosed and the predominant cause of cancer-associated death, hepatocellular carcinoma (HCC) still remains challenging to cure and demanding to better predict its prognosis (Siegel et al, 2017; Bray et al, 2018)
We focused on the predictive value of autophagy-associated hub genes and assembled an accurate prognosis signature based on the International Cancer Genome Consortium (ICGC) dataset, and the power of the model was re-confirmed by the The Cancer Genome Atlas (TCGA) dataset
Found out the expression data of HCC in ICGC and TCGA based on 232 autophagy-related genes collected from Human Autophagy Database (HADb)
Summary
As one of the most generally diagnosed and the predominant cause of cancer-associated death, hepatocellular carcinoma (HCC) still remains challenging to cure and demanding to better predict its prognosis (Siegel et al, 2017; Bray et al, 2018). During the initiation of cancer, autophagy could resist tumor proliferation by eliminating aberrant cytosolic components like altered proteins and organelles. Once the cancer has established and developed, autophagy, functioned as a cell death controller in mature cancer cells (Mathew et al, 2007; Bhutia et al, 2013), is capable of supporting tumor growth via preserving neoplasms from stressful conditions, involving necrosis and inflammation, hypoxia, and nutrient deficiency (Degenhardt et al, 2006; Lorin et al, 2013). The autophagy-related gene signature has been constructed to predict prognosis in multiple tumors, including resected pancreatic cancer (Ko et al, 2013), glioma (Zhang H. et al, 2017), and breast tumor (Gu et al, 2016). The specific relationship between autophagy and HCC has not yet been fully elucidated by far
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