LRP1 expression in colon cancer predicts clinical outcome

// Camille Boulagnon-Rombi 1, 2 , Christophe Schneider 2, 3 , Chloe Leandri 4 , Albin Jeanne 2, 5 , Virginie Grybek 6 , Aude Marchal Bressenot 2 , Coralie Barbe 7 , Benjamin Marquet 1 , Saviz Nasri 8 , Christelle Coquelet 8 , Caroline Fichel 1 , Nicole Bouland 1 , Arnaud Bonnomet 9 , Reza Kianmanesh 10 , Anne-Sophie Lebre 6 , Olivier Bouche 4 , Marie-Daniele Diebold 1, 2 , Georges Bellon 2, 11 and Stephane Dedieu 2, 3 1 Laboratoire de Biopathologie, Centre Hospitalier Universitaire et Faculte de Medecine, Reims, France 2 CNRS UMR 7369, Matrice Extracellulaire et Dynamique Cellulaire, MEDyC, Reims, France 3 Universite de Reims Champagne-Ardenne, UFR Sciences Exactes et Naturelles, Campus Moulin de la Housse, Reims, France 4 Service de Gastro-enterologie et Cancerologie Digestive, Centre Hospitalier Universitaire, Reims, France 5 SATT Nord, Lille, France 6 Laboratoire de Genetique, Centre Hospitalier Universitaire, Reims, France 7 Unite d’Aide Methodologique, Centre Hospitalier Universitaire, Reims, France 8 CRB Tumorotheque de Champagne-Ardenne, Reims, France 9 Plateforme d’Imagerie Cellulaire et Tissulaire, Universite de Reims Champagne-Ardenne, Reims, France 10 Service de Chirurgie Digestive, Centre Hospitalier Universitaire, Reims, France 11 Laboratoire de Biochimie, Centre Hospitalier Universitaire, Reims, France Correspondence to: Camille Boulagnon-Rombi, email: camille.boulagnon@gmail.com 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 BRAF V600E 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.