Low MATR3 Expression Is Associated with Poor Prognosis in Endometrial Carcinoma: An Integrated Immunohistochemical and Transcriptomic Analysis

Endometrial carcinoma (EC) is the most common malignancy of the female genital tract, yet reliable prognostic biomarkers remain limited. Matrin-3 (MATR3), a nuclear matrix protein involved in genome stability and RNA processing, has been implicated in various cancers, but its role in EC has not been described. Here, we performed an integrated analysis combining immunohistochemical evaluation of MATR3 protein expression in a retrospective institutional cohort of 112 patients with EC and in silico analysis of MATR3 mRNA expression in 172 TCGA cases. Immunohistochemical analysis revealed nuclear MATR3 expression in both EC and normal endometrial tissues, with significantly lower protein levels in EC compared to control tissues (p < 0.0001). MATR3 mRNA was significantly reduced in EC tumour tissues compared to adjacent normal tissues (p < 0.0001). Low MATR3 protein expression was associated with shorter OS after adjustment for age, histological grade, pT, pN and pM in an LVSI-stratified Cox model (HR = 2.296; 95% CI: 1.284–4.104; p = 0.0050). Low MATR3 mRNA expression was associated with improved overall survival in TCGA (median OS = 110.1 months; HR = 2.174; 95% CI: 1.066–4.43; p = 0.0303). Co-expression analysis identified BCLAF1 and TOP2B as key positive correlates, while TRAPPC5 and FASTK showed the strongest negative correlations. Genes positively correlated with MATR3 mRNA expression were enriched for nuclear transcription and RNA-processing annotations, whereas negatively correlated genes were enriched for mitochondrial processes. These associations do not establish a mechanistic link between MATR3 and pathway activity. Our findings support further investigation of MATR3 as a candidate prognostic marker in EC, with independent validation and functional studies required.