Deletion at 6q24.2-26 predicts longer survival of high-grade serous epithelial ovarian cancer patients
Por:
Kamieniak, MM, Rico, D, Milne, RL, Munoz-Repeto, I, Ibanez, K, Grillo, MA, Domingo, S, Borrego, S, Cazorla, A, Garcia-Bueno, JM, Hernando, S, Garcia-Donas, J, Hernandez-Agudo, E, Cajal, TRY, Robles-Diaz, L, Marquez-Rodas, I, Cusido, M, Saez, R, Lacambra-Calvet, C, Osorio, A, Urioste, M, Cigudosa, JC, Paz-Ares, L, Palacios, J, Benitez, J, Garcia, MJ
Publicada:
1 feb 2015
Resumen:
Standard treatments for advanced high-grade serous ovarian carcinomas (HGSOCs) show significant side-effects and provide only short-term survival benefits due to disease recurrence. Thus, identification of novel prognostic and predictive biomarkers is urgently needed. We have used 42 paraffin-embedded HGSOCs, to evaluate the utility of DNA copy number alterations, as potential predictors of clinical outcome. Copy number-based unsupervised clustering stratified HGSOCs into two clusters of different immunohistopathological features and survival outcome (HR = 0.15, 95%CI = 0.03-0.81; P-adj = 0.03). We found that loss at 6q24.2-26 was significantly associated with the cluster of longer survival independently from other confounding factors (HR = 0.06, 95%CI = 0.01-0.43, P-adj = 0.005). The prognostic value of this deletion was validated in two independent series, one consisting of 36 HGSOCs analyzed by fluorescent in situ hybridization (P = 0.04) and another comprised of 411 HGSOCs from the Cancer Genome Atlas study (TCGA) (HR = 0.67, 95% CI = 0.48-0.93, P-adj = 0.019). In addition, we confirmed the association of low expression of the genes from the region with longer survival in 799 HGSOCs (HR = 0.74, 95% CI = 0.61-0.90, log-rank P = 0.002) and 675 high-FIGO stage HGSOCs (HR = 0.76, 95% CI = 0.61-0.96, log-rank P = 0.02) available from the online tool KM-plotter. Finally, by integrating copy number, RNAseq and survival data of 296 HGSOCs from TCGA we propose a few candidate genes that can potentially explain the association. Altogether our findings indicate that the 6q24.2-26 deletion is an independent marker of favorable outcome in HGSOCs with potential clinical value as it can be analyzed by FISH on tumor sections and guide the selection of patients towards more conservative therapeutic strategies in order to reduce side-effects and improve quality of life. (C) 2014 The Authors. Published by Elsevier B.V. on behalf of Federation of European Biochemical Societies.
Filiaciones:
Kamieniak, MM:
Spanish Natl Canc Res Ctr CNIO, Human Genet Grp, Madrid 28029, Spain
Rico, D:
Spanish Natl Canc Res Ctr CNIO, Struct Computat Biol Grp, Madrid 28029, Spain
Milne, RL:
Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic 3004, Australia
Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Biostat & Epidemiol, Melbourne, Vic 3010, Australia
Munoz-Repeto, I:
Spanish Natl Canc Res Ctr CNIO, Human Genet Grp, Madrid 28029, Spain
Ibanez, K:
Spanish Natl Canc Res Ctr CNIO, Struct Computat Biol Grp, Madrid 28029, Spain
Grillo, MA:
Spanish Natl Canc Res Ctr CNIO, Mol Cytogenet Grp, Madrid 28029, Spain
Domingo, S:
Spanish Natl Canc Res Ctr CNIO, Human Genet Grp, Madrid 28029, Spain
Borrego, S:
Univ Seville, CSIC, Univ Hosp Virgen Rocio, Dept Genet, Seville 41013, Spain
Univ Seville, CSIC, Univ Hosp Virgen Rocio, Dept Reprod, Seville 41013, Spain
Univ Seville, CSIC, Univ Hosp Virgen Rocio, Dept Fetal Med, Seville 41013, Spain
Cazorla, A:
Fdn Jimenez Diaz, Dept Pathol, E-28040 Madrid, Spain
Garcia-Bueno, JM:
Hosp Gen Albacete, Dept Oncol, Albacete 02006, Spain
Hernando, S:
Fdn Hosp Alcorcon, Dept Oncol, Alcorcon 28922, Spain
Garcia-Donas, J:
Oncol Ctr Clara Campal, Med Oncol Serv, Madrid 28050, Spain
Hernandez-Agudo, E:
Spanish Natl Canc Res Ctr CNIO, Breast Canc Clin Res Unit, Madrid 28029, Spain
Cajal, TRY:
Hosp Sant Pau, Med Oncol Serv, Barcelona 08026, Spain
Robles-Diaz, L:
Hosp 12 Octubre, Familial Canc Unit, E-28041 Madrid, Spain
Hosp 12 Octubre, Dept Med Oncol, E-28041 Madrid, Spain
Marquez-Rodas, I:
Univ Complutense Calle Doctor Esquerdo, Inst Invest Sanitaria Gregorio Maranon, Med Oncol Serv, Madrid 28007, Spain
Cusido, M:
Inst Univ Dexeus, Dept Obstet & Gynecol, Barcelona 08028, Spain
Saez, R:
Hosp Donostia, Genet Lab, San Sebastian 20080, Spain
Lacambra-Calvet, C:
Hosp Sever Ochoa, Dept Internal Med, Madrid 28911, Spain
Osorio, A:
Spanish Natl Canc Res Ctr CNIO, Human Genet Grp, Madrid 28029, Spain
Biomed Network Res Ctr Rare Dis CIBERER, Madrid, Spain
Urioste, M:
Spanish Natl Canc Res Ctr CNIO, Familial Canc Clin Unit, Madrid 28029, Spain
Biomed Network Res Ctr Rare Dis CIBERER, Madrid, Spain
Cigudosa, JC:
Spanish Natl Canc Res Ctr CNIO, Mol Cytogenet Grp, Madrid 28029, Spain
Biomed Network Res Ctr Rare Dis CIBERER, Madrid, Spain
Paz-Ares, L:
Univ Hosp Virgen Rocio, Dept Med Oncol, Seville 41013, Spain
Palacios, J:
Hosp Univ Ramon & Cajal, Dept Pathol, Madrid 28034, Spain
Benitez, J:
Spanish Natl Canc Res Ctr CNIO, Human Genet Grp, Madrid 28029, Spain
Biomed Network Res Ctr Rare Dis CIBERER, Madrid, Spain
Garcia, MJ:
Spanish Natl Canc Res Ctr CNIO, Human Genet Grp, Madrid 28029, Spain
Biomed Network Res Ctr Rare Dis CIBERER, Madrid, Spain
Green Published, hybrid
|