Development and Validation of a Novel Mitophagy-Related Gene Prognostic Signature for Hepatocellular Carcinoma Based on Immunoscore Classification of Tumor

Abstract

Emerging evidence suggested that mitophagy may play an important role in the progression of hepatocellular carcinoma (HCC), whereas the association between mitophagy-related genes and HCC patients’ prognosis remains unknown. In this study, we aimed to investigate the potential prognostic values of mitophagy-related genes (MRGs) on HCC patients at the genetic level. According to median immunoscore, we categorized HCC patients from TCGA cohort into two immune score groups, while 39 differential expression MRGs were identified. By using univariate analysis, we screened out 18 survival-associated MRGs, and then, the least absolute shrinkage and selection operator (LASSO) analysis was applied to construct a prognosis model that consisted of 9 MRGs (ATG7, ATG9A, BNIP3L, GABARAPL1, HTRA2, MAP1LC3B2, TFE3, TIGAR, and TOMM70). In our prognostic model, overall survival in the high and low-risk groups was significantly different P < 0.001 , and the respective areas under the curve (AUC) of our prognostic model were 0.686 for 3-year survival in the TCGA cohort and 0.776 for 3-year survival in the ICGC cohort. Moreover, we identified the risk score as the independent factor for predicting the HCC patients’ prognosis by using single and multifactor analyses, and a nomogram was also constructed for future clinical application. Further functional analyses showed that the immune status between two risk groups was significantly different. Our findings may provide a novel mitophagy-related gene signature, and these will be better used for prognostic prediction in HCC, thus improving patient outcome.

Induction of Genes Implicated in Stress Response and Autophagy by a Novel Quinolin-8-yl-nicotinamide QN523 in Pancreatic Cancer

“…As clearly illustrated by Bru-seq trace diagrams (Figure ), QN523 increases the transcription of select autophagy-related genes WIPI1 (12.8-fold, Figure A), FAM129A (16.8-fold, Figure B), homocysteine-inducible ER protein with ubiquitin like domain 1 (HERPUD1) (9.8-fold, Figure C), GABARAPL1 (7.8-fold, Figure D), HMOX1 (13-fold, Figure E), and MAP1LC3B (6.8-fold, Figure F). WIPI1, GABARAPL1, and MAP1LC3B are well-established autophagy-related genes and relevant cancer markers at both gene and protein levels. − HERPUD1 is a part of the ER-associated degradation machinery involved in ubiquitin-dependent degradation of misfolded proteins in the ER . FAM129A an ATF4 target genes plays a direct role in autophagy. , Heme oxygenase (HMOX1) acts as a cytoprotective gene against several forms of cell death including autophagy .…”

Six mitophagy-related hub genes as peripheral blood biomarkers of Alzheimer’s disease and their immune cell infiltration correlation

“…Mitophagy as a selective degradation process, is critical to keeping mitochondria healthy, producing ATP, and maintaining neuronal activity and survival by removing impaired mitochondria. MRGs have been previously reported as prognostic or diagnostic markers for various tumors, including pancreatic cancer ( Zhuo et al, 2022 ), breast cancer ( Zhao et al, 2022 ), and liver cancer ( Chen et al, 2021 ; Xu et al, 2022 ), whereas only a limited number of studies have examined the usefulness of them as AD biomarkers. Pakpian et al (2020) recently reported that alterations in mitochondrial dynamic-related genes in the peripheral blood may be useful for diagnosing AD.…”

A Mitophagy-Related Gene Signature for Subtype Identification and Prognosis Prediction of Hepatocellular Carcinoma

“…Xu et al used 16 survival MRGs to construct the prognosis model [ 65 ]. Chen et al categorized patients into two groups according to the median immune score and searched the MRGs between the groups to construct the prognosis model, but they did not construct mitophagy-related HCC subtypes [ 66 ]. Wang et al identified HCC subtypes based on 26 selection-free MRGs, while our study identified the low-risk C1 subtype and high-risk C2 subtype based on 21 survival-related MRGs [ 67 ].…”