Prognostic Significance of CD47 and DHX9 in Metastatic Rectal Cancer
Abstract
Background/Objectives: The prognosis of metastatic rectal cancer remains poor, and few reliable prognostic biomarkers are available. DHX9 and CD47 have been implicated in colorectal cancer biology, but their prognostic value in metastatic disease remains unclear. We evaluated the associations of DHX9 and CD47 expression with clinical characteristics, molecular markers and overall survival. Methods: This retrospective, single-center cohort study included 65 patients with metastatic rectal cancer treated between 2010 and 2023. Expression of DHX9 and CD47 in primary tumor tissue was assessed by immunohistochemistry and classified as low or high. Clinical characteristics, metastatic presentation (de novo or recurrent), metastatic sites and molecular markers (KRAS, NRAS, BRAF and HER2) were recorded. Associations with marker expression were examined. Overall survival was analyzed using the Kaplan–Meier method, log-rank test and multivariable Cox proportional hazards regression adjusted for clinical and molecular factors. Results: High DHX9 expression was observed in 87.7% of tumors and high CD47 expression in 35.4%. During a median follow-up of 24 months, 53.1% of patients died. High CD47 expression was associated with shorter overall survival (log-rank p = 0.016) and this association persisted after adjustment for age, sex, metastatic presentation and DHX9 expression (HR = 2.71; 95% CI 1.34–5.48; p = 0.006). The association remained significant after further adjustment for RAS/RAF mutation status and HER2 positivity (HR = 2.78; 95% CI 1.02–7.59; p = 0.047). DHX9 expression was not associated with overall survival (log-rank p = 0.243). Expression of neither marker differed between de novo and recurrent metastatic disease or according to RAS, BRAF or HER2 status. Conclusions: In this exploratory, single-centre analysis, high CD47 expression was associated with shorter overall survival, whereas DHX9 expression was not. These hypothesis-generating findings require confirmation in larger, prospective, multicentre studies before any clinical application.