ColoLipidGene: signature of lipid metabolism-related genes to predict prognosis in stage-II colon cancer patients.

// Teodoro Vargas 1 , Juan Moreno-Rubio 2, 3 , Jesus Herranz 4 , Paloma Cejas 2, 5 , Susana Molina 1 , Margarita Gonzalez-Vallinas 1 , Marta Mendiola 2 , Emilio Burgos 5, 6 , Cristina Aguayo 5, 7 , Ana B. Custodio 5, 7 , Isidro Machado 5, 8 , David Ramos 5, 9 , Meritxell Gironella 5, 10 , Isabel Espinosa-Salinas 1 , Ricardo Ramos 11 , Roberto Martin-Hernandez 4 , Alberto Risueno 12 , Javier De Las Rivas 12 , Guillermo Reglero 1 , Ricardo Yaya 5, 13 , Carlos Fernandez-Martos 5, 13 , Jorge Aparicio 5, 14 , Joan Maurel 5, 15 , Jaime Feliu 5, 7 , Ana Ramirez de Molina 1 1 Molecular Oncology, IMDEA-Food Institute, CEI UAM+CSIC, Madrid (Spain) 2 Translational Oncology Laboratory, La Paz University Hospital (IdiPAZ), Madrid (Spain) 3 Precision Oncology Laboratory (POL), Infanta Sofia University Hospital, Madrid (Spain) 4 Biostatistics and Bioinformatics Unit, IMDEA-Food Institute, CEI UAM+CSIC, Madrid (Spain) 5 Grupo Espanol Multidisciplinar en Cancer Digestivo (GEMCAD) 6 Pathology Department, La Paz University Hospital (IdiPAZ), Madrid (Spain) 7 Medical Oncology, La Paz University Hospital (IdiPAZ), Madrid (Spain) 8 Pathology Department, Oncologic Institute of Valencia (IVO), Valencia (Spain) 9 Molecular Pathology, La Fe University Hospital, Valencia (Spain) 10 Gastrointestinal and Pancreatic Oncology, Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBEREHD), Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Hospital Clinic, Barcelona (Spain) 11 Genomics Unit, Science Park, Madrid (Spain) 12 Bioinformatics and Functional Genomics Research Group, Cancer Research Center (CSIC-USAL), Salamanca (Spain) 13 Medical Oncology, Oncologic Institute of Valencia (IVO), Valencia (Spain) 14 Medical Oncology, La Fe University Hospital, Valencia (Spain) 15 Medical Oncology and Translational Genomics Group and Targeted Therapeutics, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Hospital Clinic, Barcelona (Spain) Correspondence to: Ana Ramirez de Molina, e-mail: ana.ramirez@imdea.org Keywords: colon cancer, lipid metabolism, biomarker, prognosis Received: December 22, 2014      Accepted: January 09, 2015      Published: February 06, 2015 ABSTRACT Lipid metabolism plays an essential role in carcinogenesis due to the requirements of tumoral cells to sustain increased structural, energetic and biosynthetic precursor demands for cell proliferation. We investigated the association between expression of lipid metabolism-related genes and clinical outcome in intermediate-stage colon cancer patients with the aim of identifying a metabolic profile associated with greater malignancy and increased risk of relapse. Expression profile of 70 lipid metabolism-related genes was determined in 77 patients with stage II colon cancer. Cox regression analyses using c-index methodology was applied to identify a metabolic-related signature associated to prognosis. The metabolic signature was further confirmed in two independent validation sets of 120 patients and additionally, in a group of 264 patients from a public database. The combined analysis of these 4 genes, ABCA1, ACSL1, AGPAT1 and SCD, constitutes a metabolic-signature (ColoLipidGene) able to accurately stratify stage II colon cancer patients with 5-fold higher risk of relapse with strong statistical power in the four independent groups of patients. The identification of a group of 4 genes that predict survival in intermediate-stage colon cancer patients allows delineation of a high-risk group that may benefit from adjuvant therapy, and avoids the toxic and unnecessary chemotherapy in patients classified as low-risk group.