Predictive significance of MPT-driven necrosis-related genes signature in gastric cancer and their impact on the tumor microenvironment.

[BACKGROUND] Gastric cancer (GC) presents significant management challenges. MPT-driven necrosis (MPTDN) plays a significant role in various conditions, but its connection with GC is unclear. This study aimed to investigate the predictive significance of MPTDN-related genes (MPTDNRGs) in GC and their effect on the tumor immune microenvironment (TIME).

[METHODS] RNA sequencing data for GC were sourced from TCGA and GEO databases. The mutation profiles and MPTDNRG expression between tumor and normal samples were assessed. Prognostic mRNAs were identified using univariate Cox regression and LASSO regression. GC patients were classified into high- and low-risk groups according to risk scores, followed by survival analysis and evaluation of correlations between MPTDN score and clinicopathological features, functional pathway, TIME, and responses to immunotherapy.

[RESULTS] MPTDNRGs exhibited a 64% mutation rate in GC, with 22 showing significant expression differences. Univariate Cox and LASSO regression identified 15 independently prognostic MPTDNRGs. The prognostic risk model stratified patients into two groups, revealing significant differences in overall and disease-free survival. A nomogram incorporating the signature and clinical characteristics showed strong specificity and sensitivity in predicting prognosis. The MPTDN score was significantly associated with clinical characteristics, functional pathways, and TIME. scRNA-seq analysis indicated higher MPTDN-signature expression in CD8 + T cells, malignant cells, and myofibroblasts. TIDE analysis suggested high-risk patients have reduced responses to immunotherapy, while low-risk patients could benefit more. Importantly, validation using urothelial carcinoma data confirmed a better prognosis for low-risk patients with immunotherapy.

[CONCLUSION] This study highlights the importance of MPTDN-related signatures in predicting GC prognosis and guiding therapeutic decisions.