HEPACAM2 expression for prognostic stratification in rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy.

BACKGROUND

Identification of molecular biomarkers associated with treatment response and survival outcomes may facilitate personalized therapeutic strategies in rectal cancer. HEPACAM2 (hepatocyte cell adhesion molecule 2), a member of the immunoglobulin superfamily, has been implicated in mitotic regulation and centrosome maturation and may influence tumor progression. Therefore, this study aimed to evaluate the prognostic significance of HEPACAM2 expression in patients with rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy.

METHODS

Mining of a publicly available gene expression dataset (GSE35452) identified HEPACAM2 as one of the significantly upregulated in CRT-resistant tumors. Immunohistochemical assessment of HEPACAM2 protein expression was performed on pretreatment biopsy specimens from 343 patients with rectal adenocarcinoma who underwent neoadjuvant CRT between 1998 and 2017. Associations between HEPACAM2 expression and clinicopathological variables were examined using chi-square testing. Survival outcomes were evaluated using Kaplan-Meier estimation and Cox proportional hazards regression.

RESULTS

High HEPACAM2 expression was associated with advanced pretreatment stage, nodal involvement, increased posttreatment residual disease, vascular and perineural invasion, and poor tumor regression (all p ≤ 0.005). In both univariable and multivariable analyses, high HEPACAM2 expression independently predicted worse disease-specific survival (HR 2.663, 95% CI 1.280-4.203, p = 0.005), locoregional recurrence-free survival (HR 4.311, 95% CI 1.130-5.960, p = 0.003), and metastasis-free survival (HR 5.711, 95% CI 2.657-12.278, p < 0.001).

CONCLUSIONS

These findings suggest that HEPACAM2 expression may represent a novel prognostic biomarker for rectal adenocarcinoma, although prospective studies are required to confirm its clinical utility.