Identifying CTH and MAP1LC3B as ferroptosis biomarkers for prognostic indication in gastric cancer decoding

Abstract

Abstract Gastric cancer (GC), known for its high incidence and poor prognosis, urgently necessitates the identification of reliable prognostic biomarkers to enhance patient outcomes. We scrutinized data from 375 GC patients alongside 32 non-cancer controls, sourced from the TCGA database. A univariate Cox Proportional Hazards Model (COX) regression was employed to evaluate expressions of ferroptosis-related genes. This was followed by the application of Least Absolute Shrinkage and Selection Operator (LASSO) and multivariate COX regression for the development of prognostic models. The composition of immune cell subtypes was quantified utilizing CIBERSORT, with their distribution in GC versus control samples being comparatively analyzed. Furthermore, the correlation between the expressions of Cystathionine Gamma-Lyase (CTH) and Microtubule Associated Protein 1 Light Chain 3 Beta (MAP1LC3B) and the abundance of immune cell subtypes was explored. Our bioinformatics findings underwent validation through immunohistochemical analysis. Our prognostic models integrated CTH and MAP1LC3B. Survival analysis indicated that patients categorized as high-risk, as defined by the model, exhibited significantly lower survival rates compared to their low-risk counterparts. Notably, CTH expression inversely correlated with monocyte levels, while MAP1LC3B expression showed an inverse relationship with the abundance of M2 macrophages. Immunohistochemical validation corroborated lower expressions of CTH and MAP1LC3B in GC tissues relative to control samples, in concordance with our bioinformatics predictions. Our study suggests that the dysregulation of CTH, MAP1LC3B, and the accompanying monocyte-macrophage dynamics could be pivotal in the prognosis of GC. These elements present potential targets for prognostic assessment and therapeutic intervention.

Keywords

• Gastric cancer
• Ferroptosis
• Prognostic model
• Immune cell infiltration
• Immunohistochemistry