ColoLipidGene: signature of lipid metabolism-related genes to predict prognosis in stage-II colon cancer patients.
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.
Molecular Oncology, IMDEA-Food Institute, CEI UAM+CSIC, Madrid (Spain).
Teodoro
T
Vargas
Translational Oncology Laboratory, La Paz University Hospital (IdiPAZ), Madrid (Spain).|Precision Oncology Laboratory (POL), Infanta Sofía University Hospital, Madrid (Spain).
Juan
J
Moreno-Rubio
Biostatistics and Bioinformatics Unit, IMDEA-Food Institute, CEI UAM+CSIC, Madrid (Spain).
Jesús
J
Herranz
Translational Oncology Laboratory, La Paz University Hospital (IdiPAZ), Madrid (Spain).|Grupo Español Multidisciplinar en Cáncer Digestivo (GEMCAD).
Paloma
P
Cejas
Molecular Oncology, IMDEA-Food Institute, CEI UAM+CSIC, Madrid (Spain).
Susana
S
Molina
Molecular Oncology, IMDEA-Food Institute, CEI UAM+CSIC, Madrid (Spain).
Margarita
M
González-Vallinas
Translational Oncology Laboratory, La Paz University Hospital (IdiPAZ), Madrid (Spain).
Marta
M
Mendiola
Grupo Español Multidisciplinar en Cáncer Digestivo (GEMCAD).|Pathology Department, La Paz University Hospital (IdiPAZ), Madrid (Spain).
Emilio
E
Burgos
Grupo Español Multidisciplinar en Cáncer Digestivo (GEMCAD).|Medical Oncology, La Paz University Hospital (IdiPAZ), Madrid (Spain).
Cristina
C
Aguayo
Grupo Español Multidisciplinar en Cáncer Digestivo (GEMCAD).|Medical Oncology, La Paz University Hospital (IdiPAZ), Madrid (Spain).
Ana B
AB
Custodio
Grupo Español Multidisciplinar en Cáncer Digestivo (GEMCAD).|Pathology Department, Oncologic Institute of Valencia (IVO), Valencia (Spain).
Isidro
I
Machado
Grupo Español Multidisciplinar en Cáncer Digestivo (GEMCAD).|Molecular Pathology, La Fe University Hospital, Valencia (Spain).
David
D
Ramos
Grupo Español Multidisciplinar en Cáncer Digestivo (GEMCAD).|Gastrointestinal and Pancreatic Oncology, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Barcelona (Spain).
Meritxell
M
Gironella
Molecular Oncology, IMDEA-Food Institute, CEI UAM+CSIC, Madrid (Spain).
Isabel
I
Espinosa-Salinas
Genomics Unit, Science Park, Madrid (Spain).
Ricardo
R
Ramos
Biostatistics and Bioinformatics Unit, IMDEA-Food Institute, CEI UAM+CSIC, Madrid (Spain).
Roberto
R
Martín-Hernández
Bioinformatics and Functional Genomics Research Group, Cancer Research Center (CSIC-USAL), Salamanca (Spain).
Alberto
A
Risueño
Bioinformatics and Functional Genomics Research Group, Cancer Research Center (CSIC-USAL), Salamanca (Spain).
Javier
J
De Las Rivas
Molecular Oncology, IMDEA-Food Institute, CEI UAM+CSIC, Madrid (Spain).
Guillermo
G
Reglero
Grupo Español Multidisciplinar en Cáncer Digestivo (GEMCAD).|Medical Oncology, Oncologic Institute of Valencia (IVO), Valencia (Spain).
Ricardo
R
Yaya
Grupo Español Multidisciplinar en Cáncer Digestivo (GEMCAD).|Medical Oncology, Oncologic Institute of Valencia (IVO), Valencia (Spain).
Carlos
C
Fernández-Martos
Grupo Español Multidisciplinar en Cáncer Digestivo (GEMCAD).|Medical Oncology, La Fe University Hospital, Valencia (Spain).
Jorge
J
Aparicio
Grupo Español Multidisciplinar en Cáncer Digestivo (GEMCAD).|Medical Oncology and Translational Genomics Group and Targeted Therapeutics, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Barcelona (Spain).
Joan
J
Maurel
Grupo Español Multidisciplinar en Cáncer Digestivo (GEMCAD).|Medical Oncology, La Paz University Hospital (IdiPAZ), Madrid (Spain).
Jaime
J
Feliu
Molecular Oncology, IMDEA-Food Institute, CEI UAM+CSIC, Madrid (Spain).
Ana
A
Ramírez de Molina
D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase / Q000235:genetics / Q000378:metabolism; D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012008:Recurrence; D012044:Regression Analysis; D012189:Retrospective Studies; D013230:Stearoyl-CoA Desaturase / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome
D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; D064286:ATP Binding Cassette Transporter 1; D051792:Basic Helix-Loop-Helix Proteins; D013230:Stearoyl-CoA Desaturase; C577836:ABCA1 protein, human; C065500:ASCL1 protein, human; C523776:SCD1 protein, human; C544779:AGPAT1 protein, human
biomarker; colon cancer; lipid metabolism; prognosis