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

被引：68

作者：

Vargas, Teodoro ^{[1
]}

Moreno-Rubio, Juan ^{[2
,3
]}

Herranz, Jesus ^{[4
]}

Cejas, Paloma ^{[2
,5
]}

Molina, Susana ^{[1
]}

Gonzalez-Vallinas, Margarita ^{[1
]}

Mendiola, Marta ^{[2
]}

Burgos, Emilio ^{[5
,6
]}

Aguayo, Cristina ^{[5
,7
]}

Custodio, Ana B. ^{[5
,7
]}

Machado, Isidro ^{[5
,8
]}

Ramos, David ^{[5
,9
]}

Gironella, Meritxell ^{[10
]}

Espinosa-Salinas, Isabel ^{[1
]}

Ramos, Ricardo ^{[11
]}

Martin-Hernandez, Roberto ^{[4
]}

Risueno, Alberto ^{[12
]}

De Las Rivas, Javier ^{[12
]}

Reglero, Guillermo ^{[1
]}

Yaya, Ricardo ^{[5
,13
]}

Fernandez-Martos, Carlos ^{[5
,13
]}

Aparicio, Jorge ^{[5
,14
]}

Maurel, Joan ^{[5
,15
,16
]}

Feliu, Jaime ^{[5
,7
]}

Ramirez de Molina, Ana ^{[1
]}

机构：

[1] CEI UAM CSIC, IMDEA Food Inst, Mol Oncol, Madrid, Spain

[2] La Paz Univ Hosp IdiPAZ, Translat Oncol Lab, Madrid, Spain

[3] Infanta Sofia Univ Hosp, POL, Madrid, Spain

[4] CEI UAM CSIC, IMDEA Food Inst, Biostat & Bioinformat Unit, Madrid, Spain

[5] Grp Espanol Multidisciplinar Canc Digest GEMCAD, Barcelona, Spain

[6] La Paz Univ Hosp IdiPAZ, Dept Pathol, Madrid, Spain

[7] La Paz Univ Hosp IdiPAZ, Med Oncol, Madrid, Spain

[8] IVO, Dept Pathol, Valencia, Spain

[9] La Fe Univ Hosp, Mol Pathol, Valencia, Spain

[10] Hosp Clin Barcelona, Gastrointestinal & Pancreat Oncol, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain

[11] Genom Unit, Madrid, Spain

[12] Canc Res Ctr CSIC USAL, Bioinformat & Funct Genom Res Grp, Salamanca, Spain

[13] IVO, Med Oncol, Valencia, Spain

[14] La Fe Univ Hosp, Med Oncol, Valencia, Spain

[15] Hosp Clin Barcelona, Med Oncol & Translat Genom Grp, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain

[16] Hosp Clin Barcelona, Targeted Therapeut, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain

来源：

ONCOTARGET | 2015年 / 6卷 / 09期

关键词：

colon cancer; lipid metabolism; biomarker; prognosis; ACYL-COA SYNTHETASE; COLORECTAL-CANCER; LUNG-CANCER; EXPRESSION; SURVIVAL; INHIBITION; RECURRENCE; PATHWAYS; LIGASE-4; PROTEIN;

D O I：

10.18632/oncotarget.3130

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：7348 / 7363

页数：16

共 33 条

[1] ColoGuideEx: a robust gene classifier specific for stage II colorectal cancer prognosis [J].

Agesen, Trude H. ;

Sveen, Anita ;

Merok, Marianne A. ;

Lind, Guro E. ;

Nesbakken, Arild ;

Skotheim, Rolf I. ;

Lothe, Ragnhild A. .

GUT, 2012, 61 (11) :1560-1567

[2] Molecular pathways in colorectal cancer [J].

Al-Sohaily, Sam ;

Biankin, Andrew ;

Leong, Rupert ;

Kohonen-Corish, Maija ;

Warusavitarne, Janindra .

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 2012, 27 (09) :1423-1431

[3]

[Anonymous], 2001, HARMONICON, DOI DOI 10.1016/S0167-5729(00)00007-8

[4] Overexpression of the ATP binding cassette gene ABCA1 determines resistance to Curcumin in M14 melanoma cells [J].

Bachmeier, Beatrice E. ;

Iancu, Cristina M. ;

Killian, Peter H. ;

Kronski, Emanuel ;

Mirisola, Valentina ;

Angelini, Giovanna ;

Jochum, Marianne ;

Nerlich, Andreas G. ;

Pfeffer, Ulrich .

MOLECULAR CANCER, 2009, 8

[5] Stage II colon cancer prognosis prediction by tumor gene expression profiling [J].

Barrier, Alain ;

Boelle, Pierre-Yves ;

Roser, Francois ;

Gregg, Jennifer ;

Tse, Chantal ;

Brault, Didier ;

Lacaine, Francois ;

Houry, Sidney ;

Huguier, Michel ;

Franc, Brigitte ;

Flahault, Antoine ;

Lemoine, Antoinette ;

Dudoit, Sandrine .

JOURNAL OF CLINICAL ONCOLOGY, 2006, 24 (29) :4685-4691

[6] American society of clinical oncology recommendations on adjuvant chemotherapy for stage II colon cancer [J].

Benson, AB ;

Schrag, D ;

Somerfield, MR ;

Cohen, AM ;

Figueredo, AT ;

Flynn, PJ ;

Krzyzanowska, MK ;

Maroun, J ;

McAllister, P ;

Van Cutsem, E ;

Brouwers, M ;

Charette, M ;

Haller, DG .

JOURNAL OF CLINICAL ONCOLOGY, 2004, 22 (16) :3408-3419

[7]

Cao Y, 2001, CANCER RES, V61, P8429

[8] Molecular staging for survival prediction of colorectal cancer patients [J].

Eschrich, S ;

Yang, I ;

Bloom, G ;

Kwong, KY ;

Boulware, D ;

Cantor, A ;

Coppola, D ;

Kruhoffer, M ;

Aaltonen, L ;

Orntoft, TF ;

Quackenbush, J ;

Yeatman, TJ .

JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (15) :3526-3535

[9] Altered regulation of metabolic pathways in human lung cancer discerned by 13C stable isotope-resolved metabolomics (SIRM) [J].

Fan, Teresa W. M. ;

Lane, Andrew N. ;

Higashi, Richard M. ;

Farag, Mohamed A. ;

Gao, Hong ;

Bousamra, Michael ;

Miller, Donald M. .

MOLECULAR CANCER, 2009, 8

[10] Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study [J].

Gray, Richard ;

Barnwell, Jennifer ;

McConkey, Christopher ;

Hills, Robert K. ;

Williams, Norman S. ;

Kerr, David J. .

LANCET, 2007, 370 (9604) :2020-2029

← 1 2 3 4 →