A telomere-related gene panel predicts the prognosis and Immune Status in gastric cancer

Abstract

Telomeres play a crucial role in the development and progression of cancers. However, the impact of telomere-related genes (TRGs) on the prognosis and tumor immune microenvironment (TIME) of gastric cancer (GC) remains unclear. Therefore, a comprehensive investigation of the association between TRGs and GC is necessary. The TRG risk panel was constructed by combining differentially expressed gene analysis, weighted gene co-expression network analyses, the Least Absolute Shrinkage and Selection Operator regression, and stepwise regression analysis in the TCGA cohort and has been validated in a GEO cohort. The major impacts of the signature on the TIME and immunotherapy response were also evaluated. The prognosis model comprised 9 TRGs (CABP2, CALML6, CFAP58, DST, ELOVL2, HIST1H3G, MYF6, PDE1B and TOP3B), stratifying patients into two risk groups. Individuals with low-risk scores exhibited superior prognoses than those with high-risk scores (P < 0.001). The prognostic signature was found to be an independent factor with good predictive power for overall survival. The high-risk group tended to have higher TME scores and an inert immune status with a higher infiltration proportion of Treg cells, M2 macrophages, resting dendritic cells and resting NK cells. Additionally, the low-risk group had higher TMB, lower TIDE and a higher immunotherapy response rate. Additionally, we confirmed the expression of the nine genes in GC tissues using RT-qPCR. Our TRG-based panel has a significant role in the prognosis, TIME, and immunotherapy response. This may suggest that the TRG panel could be a powerful tool for guiding clinical treatment decisions.