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...

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Main Authors: Anaëlle Isnard, Laure‐Amandine Cramier, Rémi Vergara, Mehdi Boubaddi, Donatien Fouche, Benjamin Fernandez, Nathalie Senant, Quentin Denost, Éric Rullier, Pierre Dubus, Sandrine Dabernat, Charles Dupin, Véronique Vendrely, Anne Rullier, Samuel Amintas
Format: Article
Language:English
Published: Wiley 2025-08-01
Series:Cancer Medicine
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Online Access:https://doi.org/10.1002/cam4.71087
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author Anaëlle Isnard
Laure‐Amandine Cramier
Rémi Vergara
Mehdi Boubaddi
Donatien Fouche
Benjamin Fernandez
Nathalie Senant
Quentin Denost
Éric Rullier
Pierre Dubus
Sandrine Dabernat
Charles Dupin
Véronique Vendrely
Anne Rullier
Samuel Amintas
author_facet Anaëlle Isnard
Laure‐Amandine Cramier
Rémi Vergara
Mehdi Boubaddi
Donatien Fouche
Benjamin Fernandez
Nathalie Senant
Quentin Denost
Éric Rullier
Pierre Dubus
Sandrine Dabernat
Charles Dupin
Véronique Vendrely
Anne Rullier
Samuel Amintas
author_sort Anaëlle Isnard
collection DOAJ
description 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.
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spelling doaj-art-e1a70d2b9dfe4e72a58e6fc4b8fc4e282025-08-20T03:46:34ZengWileyCancer Medicine2045-76342025-08-011415n/an/a10.1002/cam4.71087Association Between CD147 Expression, RAS Mutational Status, and Local Recurrence in Resected Locally Advanced Rectal CancerAnaëlle Isnard0Laure‐Amandine Cramier1Rémi Vergara2Mehdi Boubaddi3Donatien Fouche4Benjamin Fernandez5Nathalie Senant6Quentin Denost7Éric Rullier8Pierre Dubus9Sandrine Dabernat10Charles Dupin11Véronique Vendrely12Anne Rullier13Samuel Amintas14CHU Bordeaux, Tumor Biology and Tumor Bank Laboratory Pessac FranceSurgical Pathology Department CHU Bordeaux Bordeaux FranceSurgical Pathology Department CHU Bordeaux Bordeaux FranceBRIC (BoRdeaux Institute of onCology), UMR1312, INSERM, University of Bordeaux Bordeaux FranceDigestive Surgery Department CHU Bordeaux Pessac FranceBRIC (BoRdeaux Institute of onCology), UMR1312, INSERM, University of Bordeaux Bordeaux FranceHistopathology Platform, TBM‐Core, University of Bordeaux Bordeaux FranceBordeaux Colorectal Institute Bordeaux FranceBRIC (BoRdeaux Institute of onCology), UMR1312, INSERM, University of Bordeaux Bordeaux FranceCHU Bordeaux, Tumor Biology and Tumor Bank Laboratory Pessac FranceBRIC (BoRdeaux Institute of onCology), UMR1312, INSERM, University of Bordeaux Bordeaux FranceBRIC (BoRdeaux Institute of onCology), UMR1312, INSERM, University of Bordeaux Bordeaux FranceBRIC (BoRdeaux Institute of onCology), UMR1312, INSERM, University of Bordeaux Bordeaux FranceSurgical Pathology Department CHU Bordeaux Bordeaux FranceCHU Bordeaux, Tumor Biology and Tumor Bank Laboratory Pessac FranceABSTRACT 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.https://doi.org/10.1002/cam4.71087BRAFCD147EMMPRINgenderKRASlocal recurrence
spellingShingle Anaëlle Isnard
Laure‐Amandine Cramier
Rémi Vergara
Mehdi Boubaddi
Donatien Fouche
Benjamin Fernandez
Nathalie Senant
Quentin Denost
Éric Rullier
Pierre Dubus
Sandrine Dabernat
Charles Dupin
Véronique Vendrely
Anne Rullier
Samuel Amintas
Association Between CD147 Expression, RAS Mutational Status, and Local Recurrence in Resected Locally Advanced Rectal Cancer
Cancer Medicine
BRAF
CD147
EMMPRIN
gender
KRAS
local recurrence
title Association Between CD147 Expression, RAS Mutational Status, and Local Recurrence in Resected Locally Advanced Rectal Cancer
title_full Association Between CD147 Expression, RAS Mutational Status, and Local Recurrence in Resected Locally Advanced Rectal Cancer
title_fullStr Association Between CD147 Expression, RAS Mutational Status, and Local Recurrence in Resected Locally Advanced Rectal Cancer
title_full_unstemmed Association Between CD147 Expression, RAS Mutational Status, and Local Recurrence in Resected Locally Advanced Rectal Cancer
title_short Association Between CD147 Expression, RAS Mutational Status, and Local Recurrence in Resected Locally Advanced Rectal Cancer
title_sort association between cd147 expression ras mutational status and local recurrence in resected locally advanced rectal cancer
topic BRAF
CD147
EMMPRIN
gender
KRAS
local recurrence
url https://doi.org/10.1002/cam4.71087
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