Abstract
BackgroundHepatocellular carcinoma (HCC) is the seventh most common malignancy and the second most common cause of cancer-related deaths. Autophagy plays a crucial role in the development and progression of HCC.MethodsUnivariate and Lasso Cox regression analyses were performed to determine a gene model that was optimal for overall survival (OS) prediction. Patients in the GSE14520 and GSE54236 datasets of the Cancer Genome Atlas (TCGA) were divided into the high-risk and low-risk groups according to established ATG models. Univariate and multivariate Cox regression analyses were used to identify risk factors for OS for the purpose of constructing nomograms. Calibration and receiver operating characteristic (ROC) curves were used to evaluate model performance. Real-time PCR was used to validate the effects of the presence or absence of an autophagy inhibitor on gene expression in HepG2 and Huh7 cell lines.ResultsOS in the high-risk group was significantly shorter than that in the low-risk group. Gene set enrichment analysis (GSEA) indicated that the association between the low-risk group and autophagy- as well as immune-related pathways was significant. ULK2, PPP3CC, and NAFTC1 may play vital roles in preventing HCC progression. Furthermore, tumor environment analysis via ESTIMATION indicated that the low-risk group was associated with high immune and stromal scores. Based on EPIC prediction, CD8+ T and B cell fractions in the TCGA and GSE54236 datasets were significantly higher in the low-risk group than those in the high-risk group. Finally, based on the results of univariate and multivariate analyses three variables were selected for nomogram development. The calibration plots showed good agreement between nomogram prediction and actual observations. Inhibition of autophagy resulted in the overexpression of genes constituting the gene model in HepG2 and Huh7 cells.ConclusionsThe current study determined the role played by autophagy-related genes (ATGs) in the progression of HCC and constructed a novel nomogram that predicts OS in HCC patients, through a combined analysis of TCGA and gene expression omnibus (GEO) databases.
Highlights
Autophagy is a conserved intracellular degradation process by which cell components, such as cellular organelles, proteins, and invading microbes, are degraded in lysosomes to provide basic materials and energy for cells
The objective of the current study was to determine the role of autophagy-related genes (ATGs) in the progression of Hepatocellular carcinoma (HCC), construct a novel nomogram capable of predicting overall survival (OS) in HCC patients and identify the mechanism underlying these processes via a combined analysis of data from the TCGA and gene expression omnibus (GEO)
Of the 487 ATGs, 60 differentially expressed genes (DEAs) were identified in the TCGA dataset based on the following criteria:
Summary
Autophagy is a conserved intracellular degradation process by which cell components, such as cellular organelles, proteins, and invading microbes, are degraded in lysosomes to provide basic materials and energy for cells. It serves as a double-edged sword in tumorigenesis and metastasis. Inhibition of autophagy elevates the inflammatory response, thereby promoting cancer progression [7,8,9]. Previous studies have indicated that autophagy supports the survival and proliferation of cancer cells and metastasis-related behavior [12]. Autophagy plays a dual role in cancer development and progression. Autophagy plays a crucial role in the development and progression of HCC
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