Association Between CD147 Expression, RAS Mutational Status, and Local Recurrence in Resected Locally Advanced Rectal Cancer

TL;DR

This study investigates whether CD147 expression and RAS mutations are linked to local recurrence in rectal cancer patients after treatment.

Contribution

The study reveals a notable association between RAS mutations and CD147 expression in male rectal cancer patients.

Findings

CD147 expression and mutational status were not associated with local recurrence in rectal cancer.

RAS mutations were notably associated with elevated CD147 expression in male patients.

The association was confirmed in an independent validation cohort of 86 rectal cancer patients.

Abstract

About 5% to 10% of rectal cancer (RC) patients experience local disease recurrence after chemoradiotherapy (CRT) and surgery. Identifying patients at high risk of local recurrence (LR) could lead to the personalized management of the patients. Multiple clinicopathological parameters are associated with LR. However, the potential of tumors for local regrowth may partially lie in the expression of pro‐tumoral factors and genetic characteristics. In this work, we aimed to evaluate the association of tumor CD147 expression, a well‐described cancer aggressiveness biomarker, and mutational status, with post‐resection RC LR.

We retrospectively analyzed all patients experiencing LR after CRT and resection at Bordeaux University Hospital (2010 to 2019) and matched a LR‐negative control cohort. CD147 expression was evaluated by immunohistochemistry on post‐neoadjuvant treatment residual tumors. Mutational status was assessed by next‐generation sequencing. Correlations with LR rates were evaluated.

The analysis included 29 patients with recurrences and 60 without. The pathological node invasion stage (p = 0.023) and the median number of invaded nodes (p = 0.008) were significantly associated with LR. CD147 expression and mutational status were not associated with LR. Nonetheless, a notable association was observed between RAS mutation and elevated CD147 expression, particularly in male patients (p = 0.005). We confirmed this association in an independent validation cohort of 86 RC patients.

CD147 tumor expression levels and mutational status do not appear to be associated with resected RC LR. However, the association between RAS mutational status and CD147 expression in male patients tends to confirm the relationship between RAS activating mutations and tumor aggressiveness, as well as their sex‐related impact on colorectal tumor biology.

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