A mitochondrial permeability transition-associated lncRNA signature predicts prognosis and the immune response in gastric cancer

Gastric cancer (GC) ranks among the most prevalent malignancies globally, with persistently high and increasing incidence and mortality rates. The mitochondrial permeability transition (MPT) is pivotal in deciding whether cells perish or persist, and long non-coding RNAs (lncRNAs) function as key regulators shaping cancer progression. In this research, an MPT-associated lncRNA-based prognostic model was developed, and the patterns of immune cell infiltration in GC were explored. First, lncRNAs associated with MPT were identified, the data of which were from 407 GC patients. Next, a predictive model was developed and rigorously assessed for precision and dependability using various analytical techniques. These included Cox proportional hazards regression, Kaplan - Meier survival estimates, and receiver operating characteristic (ROC) curve evaluation to ensure robust validation. In addition, further studies were conducted, including gene function enrichment analysis, immune infiltration pattern assessment, tumor mutation burden (TMB) analysis, and drug sensitivity evaluation. Finally, PINK1 - AS function was confirmed in GC cell lines through in vitro validation. An efficient predictive model was developed, adeptly categorizing patients into high- and low-risk categories, demonstrating notable disparities in survival outcomes. The model demonstrated independence and efficacy across clinical factors and disease stages. Principal components analysis (PCA) confirmed the effectiveness of risk stratification, and a clinical nomogram was developed for survival prediction. Gene function enrichment analysis revealed the involvement of differentially expressed genes (DEGs) and lncRNAs in immune processes and cancer pathways. Immune infiltration analysis revealed distinct patterns of immune cells between the risk groups. Patients with high risk exhibited elevated TMB levels and poorer survival outcomes. Sensitivity analysis of medications indicated varied drug reactions across the risk categories. In vitro studies have revealed that PINK1-AS facilitates the progression of GC cell lines. The MPT-related lncRNA model holds promises for predicting GC prognosis and optimizing treatment strategies. However, further validation is needed to determine its clinical potential.