ИСТИНА

Background & Objectives: Gastric cancer remains a leading cause of cancer-related mortality globally, characterized by high incidence and heterogeneous outcomes necessitating reliable prognostic markers. This study aims to identify independent immunohistochemical (IHC) predictors of survival in gastric cancer patients untreated with immunotherapy, using the Cox proportional hazards model to assess intrinsic tumor biology. Methods: We evaluated 310 patients with gastric cancer who underwent surgical resection as primary treatment, without prior or subsequent immunotherapy. Tumors were histologically classified per Lauren: 119 intestinal, 114 intermediate, and 77 diffuse. A panel of 21 IHC markers—including mismatch repair proteins (MSH2, MSH6, MLH1, PMS2), PD-L1 (SP142 clone), E-cadherin, β-catenin, and others (e.g., HER2, p53)—was analyzed alongside Epstein-Barr virus (EBER) small RNA expression. Clinicopathological variables (age, sex, TNM stage, Lauren type) were correlated with survival outcomes using Cox regression analysis. Results: Male gender was associated with a 2.02-fold higher mortality risk (p<0.001), each additional year of age increased risk by 1.02-fold (p=0.02), N- stage (lymph node metastasis) by 1.61-fold (p<0.001), and M-stage (distant metastasis) by 2.52-fold (p<0.001); other clinicopathological traits were non- significant (p>0.05). Notably, MMR-negative status reduced mortality risk twofold (p=0.05), possibly due to increased tumor immunogenicity from elevated mutation burden. PD-L1 positivity (SP142) lowered mortality risk 4.35-fold (p=0.005), potentially by modulating immune suppression in the tumor microenvironment. In contrast, aberrant E-cadherin (p=0.019) and β-catenin (p=0.001) expression emerged as adverse prognostic factors, likely linked to Wnt pathway activation driving tumor aggressiveness. These findings highlight novel prognostic roles in untreated patients. Conclusion: Among gastric cancer patients not receiving immunotherapy, positive PD-L1 (SP142) and negative MMR status independently predict significantly better survival outcomes, whereas aberrant E-cadherin and β-catenin expression indicate poorer prognosis. These insights enhance risk stratification and suggest new avenues for personalized therapeutic strategies in future research.