Development of a novel autophagy-related gene model for gastric cancer prognostic prediction

Abstract

Gastric cancer (GC) is a major global health issue and one of the leading causes of tumor-associated mortality worldwide. Autophagy is thought to play a critical role in the development and progression of GC, and this process is controlled by a set of conserved regulators termed autophagy-related genes (ATGs). However, the complex contribution of autophagy to cancers is not completely understood. Accordingly, we aimed to develop a prognostic model based on the specific role of ATGs in GC to improve the prediction of GC outcomes. First, we screened 148 differentially expressed ATGs between GC and normal tissues in The Cancer Genome Atlas (TCGA) cohort. Consensus clustering in these ATGs was performed, and based on that, 343 patients were grouped into two clusters. According to Kaplan–Meier survival analysis, cluster C2 had a worse prognosis than cluster C1. Then, a disease risk model incorporating nine differentially expressed ATGs was constructed based on the least absolute shrinkage and selection operator (LASSO) regression analysis, and the ability of this model to stratify patients into high- and low-risk groups was verified. The predictive value of the model was confirmed using both training and validation cohorts. In addition, the results of functional enrichment analysis suggested that GC risk is correlated with immune status. Moreover, autophagy inhibition increased sensitivity to cisplatin and exacerbated reactive oxygen species accumulation in GC cell lines. Collectively, the results indicated that this novel constructed risk model is an effective and reliable tool for predicting GC outcomes and could help with individual treatment through ATG targeting.

Regulation of NCOA4-mediated iron recycling ameliorates paraquat-induced lung injury by inhibiting ferroptosis

“…The occurrence of autophagy is complicated associating with more than 30 autophagy-related genes (ATG). Microtubule-associated protein light chain 3 (LC3), the most commonly used autophagy-related marker, has two subforms, LC3-I and LC3-II, and the conversion of LC3-I into LC3-II is a key step in the formation of autophagosome [34,35]. Autophagy has been regarded to play a dual role in the pathological process, acting as an adaptive response to protect tissue from stress, but excessive stimulation of autophagy can be lethal for the excess elimination of cytoplasmic content [27].…”

Identification of mitochondrial respiratory chain signature for predicting prognosis and immunotherapy response in stomach adenocarcinoma

“…Ferroptosis is a newly identified programmed cell death, typically characterized by free iron overload and lethal phospholipid peroxide generation. Increasing evidence has demonstrated that inducing ferroptosis represents a promising therapeutic strategy that preferentially targets iron-rich cancer cells such as HCC [ 67 , 68 ], NSCLC [ 69 ], PDAC [ 70 ], leukemia [ 38 ] and GC [ 71 , 72 ], and provides insights into reversing drug resistance in cancers. The mitochondrial electron transport chain is responsible for ATP production.…”