Oncotarget

Research Papers: Pathology:

LRP1 expression in colon cancer predicts clinical outcome

Camille Boulagnon-Rombi _, Christophe Schneider, Chloé Leandri, Albin Jeanne, Virginie Grybek, Aude Marchal Bressenot, Coralie Barbe, Benjamin Marquet, Saviz Nasri, Christelle Coquelet, Caroline Fichel, Nicole Bouland, Arnaud Bonnomet, Reza Kianmanesh, Anne-Sophie Lebre, Olivier Bouché, Marie-Danièle Diebold, Georges Bellon and Stéphane Dedieu

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Oncotarget. 2018; 9:8849-8869. https://doi.org/10.18632/oncotarget.24225

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Abstract

Camille Boulagnon-Rombi1,2, Christophe Schneider2,3, Chloé Leandri4, Albin Jeanne2,5, Virginie Grybek6, Aude Marchal Bressenot2, Coralie Barbe7, Benjamin Marquet1, Saviz Nasri8, Christelle Coquelet8, Caroline Fichel1, Nicole Bouland1, Arnaud Bonnomet9, Reza Kianmanesh10, Anne-Sophie Lebre6, Olivier Bouché4, Marie-Danièle Diebold1,2, Georges Bellon2,11 and Stéphane Dedieu2,3

1Laboratoire de Biopathologie, Centre Hospitalier Universitaire et Faculté de Médecine, Reims, France

2CNRS UMR 7369, Matrice Extracellulaire et Dynamique Cellulaire, MEDyC, Reims, France

3Université de Reims Champagne-Ardenne, UFR Sciences Exactes et Naturelles, Campus Moulin de la Housse, Reims, France

4Service de Gastro-entérologie et Cancérologie Digestive, Centre Hospitalier Universitaire, Reims, France

5SATT Nord, Lille, France

6Laboratoire de Génétique, Centre Hospitalier Universitaire, Reims, France

7Unité d’Aide Méthodologique, Centre Hospitalier Universitaire, Reims, France

8CRB Tumorothèque de Champagne-Ardenne, Reims, France

9Plateforme d’Imagerie Cellulaire et Tissulaire, Université de Reims Champagne-Ardenne, Reims, France

10Service de Chirurgie Digestive, Centre Hospitalier Universitaire, Reims, France

11Laboratoire de Biochimie, Centre Hospitalier Universitaire, Reims, France

Correspondence to:

Camille Boulagnon-Rombi, email: [email protected]

Keywords: colorectal cancer; LRP1; miR-205; BRAF; microsatellite instability; Pathology

Received: May 11, 2017     Accepted: January 09, 2018     Published: January 13, 2018

ABSTRACT

LRP1 (low-density lipoprotein receptor-related protein 1), a multifunctional endocytic receptor, has recently been identified as a hub within a biomarker network for multi-cancer clinical outcome prediction. As its role in colon cancer has not yet been characterized, we here investigate the relationship between LRP1 and outcome.

Materials and Methods: LRP1 mRNA expression was determined in colon adenocarcinoma and paired colon mucosa samples, as well as in stromal and tumor cells obtained after laser capture microdissection. Clinical potential was further investigated by immunohistochemistry in a population-based colon cancer series (n = 307). LRP1 methylation, mutation and miR-205 expression were evaluated and compared with LRP1 expression levels.

Results: LRP1 mRNA levels were significantly lower in colon adenocarcinoma cells compared with colon mucosa and stromal cells obtained after laser capture microdissection. Low LRP1 immunohistochemical expression in adenocarcinomas was associated with higher age, right-sided tumor, loss of CDX2 expression, Annexin A10 expression, CIMP-H, MSI-H and BRAFV600E mutation. Low LRP1 expression correlated with poor clinical outcome, especially in stage IV patients. While LRP1 expression was downregulated by LRP1 mutation, LRP1 promoter was never methylated.

Conclusions: Loss of LRP1 expression is associated with worse colon cancer outcomes. Mechanistically, LRP1 mutation modulates LRP1 expression.


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