Combined Prognostic Significance of ARID1A Expression and Metastatic Lymph Node Ratio in Predicting Outcomes of Colorectal Cancer

This study investigated the prognostic significance of AT-rich interactive domain 1A (ARID1A) protein expression and the metastatic lymph node ratio (mLNR) in colorectal cancer (CRC). Immunohistochemical analysis of 78 primary resected CRC specimens revealed that 85.9% exhibited low ARID1A expression, as determined by histological (H)-score and quantitative assessment. High mLNR was observed in 17.9% of cases. Notably, low ARID1A expression combined with high mLNR was significantly associated with advanced AJCC stage, increased lymph node involvement (pN stage), lymph node metastasis (LNM), lymphovascular invasion, and comorbidities. Kaplan-Meier survival analysis demonstrated that both low ARID1A expression and high mLNR were significantly associated with reduced progression-free survival (PFS). Univariable Cox proportional hazards regression identified mLNR, AJCC stage, pN stage, distant metastasis (pM stage), and LNM as significant predictors of shorter PFS. Multivariable analysis further identified mLNR and pM stage as independent prognostic factors. In addition, GEPIA2-based transcriptomic analysis revealed significant correlations between ARID1A and LNM-associated genes, such as insulin-like growth factor 1 receptor (IGF1R), heat shock protein 47 (HSP47), and vascular endothelial growth factor C (VEGF-C). These genes also showed significant prognostic relevance for survival outcomes in patients with colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ) cohorts within the TCGA database. In conclusion, diminished ARID1A expression and elevated mLNR are associated with aggressive tumor features and poorer prognosis, suggesting their potential utility as combined prognostic biomarkers in CRC. HIGHLIGHTS Low ARID1A and high mLNR link to aggressive features in colorectal cancer. ARID1A loss and mLNR elevation predict poor progression-free survival in CRC. mLNR and pM stage emerge as independent prognostic factors in multivariable analysis. ARID1A correlates with LNM-associated genes (IGF1R, HSP47, VEGF-C) tied to poor survival in TCGA. The combined assessment of ARID1A and mLNR improves outcome prediction in patients with colorectal cancer. GRAPHICAL ABSTRACT