The interaction effect between key autophagy-related biomarkers and HBV/HCV infections on the survival prognosis of hepatocellular carcinoma

Abstract

Aim: This study aimed to investigate the prognostic and diagnostic value of autophagy-related genes (ATGs) in hepatocellular carcinoma (HCC).

Methods: The expression profiles of differentially expressed ATGs (DEAs) were extracted from The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA), International Cancer Genome Consortium (ICGC), and TIMER databases. The biological functions and enrichment pathways related to the DEAs were determined. In the TCGA training cohort, univariate Cox regression was used to define HCC subtypes, and prognostic ATGs were submitted to LASSO Cox analyses to generate overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), and disease-specific survival (DSS)-related models. The ICGC validation cohort [the Liver Cancer-RIKEN JP (LIRI-JP)] was used to examine the predictive models. The Kaplan Meier, nomogram, and receiver operating characteristic (ROC) analyses were used to confirm the accuracy of the prediction. The relationship between prognostic signature and clinicopathologic parameters, genetic alterations, tumor microenvironment, and subcellular location annotation was also examined by multiple databases.

Results: A total of 50 DEAs were identified and enriched in autophagosome membrane, programmed cell death, and PI3K-Akt signaling pathways. BIRC5, GAPDH, FKBP1A, and RAC1 were significantly correlated with poor prognosis and were identified to be independent predictors for HCC OS and DSS (HR > 1.8, P < 0.05). The risk score of prognostic models has confirmed that BIRC5 was an independent prognostic factor. The calibration curve has validated the accuracy and reliability of the nomogram for survival years, as well as ICGC validation using the same risk models. BIRC5 may influence the mortality of hepatitis B and C patients. Immunohistochemistry showed that BIRC5 protein was moderately expressed in HCC and may influence tumor detection and genetic mutations. High amplification of BIRC5 may inhibit the immune infiltrates as CD4 T cells, macrophages, and neutrophils.

Conclusion:BIRC5 is overexpressed in HCC tissues, indicating a poor prognosis that could be a new prognostic biomarker, treatment target, and diagnostic signature for HCC.

Keywords

Hepatocellular carcinoma / autophagy / BIRC5 / prognosis / biomarker

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