High PMS2 Expression-Based Nomogram for Risk Stratification in Resected Hepatocellular Carcinoma: Application to...

Hepatocellular carcinoma (HCC) progresses rapidly with a poor prognosis due to the lack of reliable recurrence risk markers. Accurate prognostic stratification and individualized recurrence prediction remain major clinical challenges, hindering treatment optimization, particularly for adjuvant or neoadjuvant therapy. Although defects in mismatch repair (MMR) mechanisms are well studied, the role of elevated MMR protein expression-particularly post-meiotic segregation increased 2 (PMS2)-has remained unclear. This study aimed to investigate the prognostic value of PMS2 overexpression and develop an integrated predictive model to improve risk stratification and guide therapy selection. We analyzed 173 HCC patients and demonstrated that elevated PMS2 expression was significantly associated with poorer disease-free survival (DFS) (p < 0.001) and overall survival (OS) (p < 0.001). Cellular and animal models confirmed the pro-proliferative role of PMS2 in HCC progression. Multivariate analysis identified high PMS2 expression [HR: 3.109 (2.019-4.786), p < 0.001], high Phosphorylated-Protein Kinase B (p-AKT) expression [HR: 2.201 (1.304-3.715), p = 0.003], Barcelona Clinic Liver Cancer (BCLC) stage [HR: 2.635 (1.156-5.992), p = 0.021], and poor pathological differentiation [HR: 1.729 (1.098-2.722), p = 0.018] as independent risk factors for poor DFS. The nomogram based on these factors demonstrated good predictive performance and effectively stratified patients into high-risk and low-risk groups (p < 0.001). In an exploratory analysis of a separate cohort receiving neoadjuvant immunotherapy, preliminary data suggested that high-risk patients might derive greater survival benefit (p=0.044). These findings highlight PMS2 overexpression as a potential prognostic biomarker and provide a promising predictive tool for personalized treatment planning in HCC, warranting further validation in prospective studies.