Evaluation of serum folate receptor alpha levels in colon cancer: Association with diagnosis, clinical stage, and metastasis.

Abstract

e15052 Background: Folate and folate receptor alpha (FRα) are critical for cell proliferation and DNA synthesis. FRα is overexpressed in various malignancies, including ovarian and lung cancer. This study aimed to analyze serum folate and FRα levels in colon cancer patients and evaluate their association with diagnosis, staging, and metastasis. Methods: This prospective case-control study included 77 patients with colon cancer and 81 healthy controls. Serum folate and Folate Receptor Alpha (FRα) levels were measured by ELISA method, and statistical comparisons were made between cancer and control groups. The associations between these biomarkers and tumor stage, metastasis status, Neutrophil-to-Lymphocyte Ratio (NLR) levels were evaluated in the colon cancer cohort. Results: Demographic and clinical characteristics of the groups are presented in Table 1. Serum FRα levels were elevated in colon cancer versus controls (p < 0.001), while serum folate levels were reduced (p < 0.001). Multivariate logistic regression identified serum FRα as an independent predictor of colon cancer (p = 0.019), after adjusting for sex, age, and folate status. After Propensity Score Matching based on age, median serum FRα in the colon cancer group was 3244.01 pg/mL (IQR: 2603.45 – 4301.04 pg/mL), higher than matched controls (median: 2340.20 pg/mL, IQR: 2028.70 – 3520.41 pg/mL). This confirmed FRα levels remained significant after age adjustment (Wilcoxon Signed-Rank Test, p = 0.016), indicating elevated serum FRα is associated with colon cancer. Post-hoc analyses showed FRα expression was higher in Stage 4 patients versus Stage 2 and 3 disease (p = 0.005), with increased levels in metastatic cases (p = 0.001). FRα levels were elevated in liver metastasis compared to extrahepatic metastases (p < 0.001). ROC analysis indicated moderate diagnostic potential (AUC: 0.665) but high sensitivity (83.1%). The predictive value for metastasis was stronger (AUC: 0.727), with serum levels elevated in liver versus extrahepatic spread (p < 0.001). Elevated FRα levels were associated with high NLR≥3 (p = 0.014). Conclusions: This study is the first prospective investigation showing elevated serum FRα levels in colon cancer, particularly in patients with liver metastases and stage 4 disease. While serum FRα showed high sensitivity for colon cancer detection, its limited specificity suggests it cannot serve as a standalone diagnostic marker. However, its predictive value for metastatic disease was stronger, with significantly higher levels in liver metastasis compared to extrahepatic spread. The demonstration of elevated serum FRα in hepatic metastasis highlights its prognostic value and potential as a non-invasive tool for identifying aggressive phenotypes and guiding FRα-targeted therapies in advanced colon cancer.