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

Abstract

Aim: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: BRAF; CD147; EMMPRIN; KRAS; gender; local recurrence; rectal cancer.

FIGURE 1

Immunohistochemical staining of CD147 in rectal cancer tissues. Panels (A–D) illustrate the four levels of staining intensity observed for CD147 using the clone 8D6 antibody. (A) No detectable staining (colorless/null), (B) low staining intensity with weak and focal staining, (C) moderate and diffuse staining intensity, and (D) high/strong and widespread staining intensity. Staining was performed on formalin‐fixed, paraffin‐embedded tissue sections, with hematoxylin counterstaining. Magnification: ×100.