A DNA damage repair gene-associated signature predicts responses of patients with advanced soft-tissue sarcoma to treatment with trabectedin

被引：13

作者：

Moura, David S. ^{[1
]}

Pena-Chilet, Maria ^{[1
,2
,3
]}

Cordero Varela, Juan Antonio ^{[1
]}

Alvarez-Alegret, Ramiro ^{[4
]}

Agra-Pujol, Carolina ^{[5
]}

Izquierdo, Francisco ^{[6
]}

Ramos, Rafael ^{[7
]}

Ortega-Medina, Luis ^{[8
]}

Martin-Davila, Francisco ^{[9
]}

Castilla-Ramirez, Carolina ^{[10
]}

Nieves Hernandez-Leon, Carmen ^{[11
]}

Romagosa, Cleofe ^{[12
]}

Vaz Salgado, Maria Angeles ^{[13
]}

Lavernia, Javier ^{[14
]}

Bague, Silvia ^{[15
]}

Mayodormo-Aranda, Empar ^{[16
]}

Vicioso, Luis ^{[17
]}

Hernandez Barcelo, Jose Emilio ^{[18
]}

Rubio-Casadevall, Jordi ^{[19
]}

de Juan, Ana ^{[20
]}

Fiano-Valverde, Maria Concepcion ^{[21
]}

Hindi, Nadia ^{[1
,22
,23
,24
]}

Lopez-Alvarez, Maria ^{[1
]}

Lacerenza, Serena ^{[1
]}

Dopazo, Joaquin ^{[1
,2
,3
,25
]}

Gutierrez, Antonio ^{[26
]}

Alvarez, Rosa ^{[27
]}

Valverde, Claudia ^{[28
]}

Martinez-Trufero, Javier ^{[29
]}

Martin-Broto, Javier ^{[1
,22
,23
,24
]}

机构：

[1] Univ Seville, Inst Biomed Seville IBIS, CSIC, HUVR, Seville, Spain

[2] Hosp Virgen del Rocio, Fdn Progreso & Salud FPS, CDCA, Clin Bioinformat Area, Seville, Spain

[3] Hosp Virgen del Rocio, Ctr Invest Biomed Red Enfermedades Raras CIBERER, FPS, Bioinformat Rare Dis BiER, Seville, Spain

[4] Miguel Servet Univ Hosp, Pathol Dept, Zaragoza, Spain

[5] Gregorio Maranon Univ Hosp, Pathol Dept, Madrid, Spain

[6] Complejo Asistencial Univ Leon, Pathol Anat Serv, Leon, Spain

[7] Son Espases Univ Hosp, Pathol Dept, Mallorca, Spain

[8] Hosp Clin San Carlos, Pathol Dept, Madrid, Spain

[9] Ciudad Real Gen Hosp, Pathol Dept, Ciudad Real, Spain

[10] Univ Hosp Virgen del Rocio, Pathol Dept, Seville, Spain

[11] Canarias Univ Hosp, Pathol Dept, Santa Cruz De Tenerife, Spain

[12] Vall dHebron Univ Hosp, Pathol Dept, Barcelona, Spain

[13] Ramon y Cajal Univ Hosp, Med Oncol Dept, Madrid, Spain

[14] Inst Valenciano Oncol, Med Oncol Dept, Valencia, Spain

[15] Hosp Santa Creu & Sant Pau, Pathol Serv, Barcelona, Spain

[16] Hosp Univ & Politecn La Fe, Pathol Dept, Valencia, Spain

[17] Virgen de la Victoria Univ Hosp, Pathol Dept, Malaga, Spain

[18] Virgen de la Arrixaca Univ Hosp, Pathol Dept, Murcia, Spain

[19] Hosp Josep Trueta, Catalan Inst Oncol, Med Oncol Dept, Girona, Spain

[20] Marques de Valdecilla Univ Hosp, Med Oncol Dept, Santander, Spain

[21] Alvaro Cunqueiro Hosp, Dept Histopathol, Univ Hosp Complex Vigo, Vigo, Spain

[22] Univ Hosp Fdn Jimenez Diaz, Med Oncol Dept, Madrid, Spain

[23] Univ Hosp Gen Villalba, Madrid, Spain

[24] Inst Invest Sanitaria Fdn Jimenez Diaz IIS FJD, Madrid, Spain

[25] Hosp Virgen del Rocio, FPS, INB ELIXIR Es, Seville, Spain

[26] Son Espases Univ Hosp, Hematol Dept, Mallorca, Spain

[27] Gregorio Maranon Univ Hosp, Med Oncol Dept, Madrid, Spain

[28] Vall dHebron Univ Hosp, Med Oncol Dept, Barcelona, Spain

[29] Miguel Servet Univ Hosp, Med Oncol Dept, Zaragoza, Spain

来源：

MOLECULAR ONCOLOGY | 2021年 / 15卷 / 12期

关键词：

gene signature; predictive biomarkers; trabectedin; MYXOID LIPOSARCOMA; CLINICAL BENEFIT; PHASE-II; TRANSCRIPTION; ANTITUMOR; ECTEINASCIDIN-743; EXPRESSION; MECHANISM; CLONING; ERCC1;

D O I：

10.1002/1878-0261.12996

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Predictive biomarkers of trabectedin represent an unmet need in advanced soft-tissue sarcomas (STS). DNA damage repair (DDR) genes, involved in homologous recombination or nucleotide excision repair, had been previously described as biomarkers of trabectedin resistance or sensitivity, respectively. The majority of these studies only focused on specific factors (ERCC1, ERCC5, and BRCA1) and did not evaluate several other DDR-related genes that could have a relevant role for trabectedin efficacy. In this retrospective translational study, 118 genes involved in DDR were evaluated to determine, by transcriptomics, a predictive gene signature of trabectedin efficacy. A six-gene predictive signature of trabectedin efficacy was built in a series of 139 tumor samples from patients with advanced STS. Patients in the high-risk gene signature group showed a significantly worse progression-free survival compared with patients in the low-risk group (2.1 vs 6.0 months, respectively). Differential gene expression analysis defined new potential predictive biomarkers of trabectedin sensitivity (PARP3 and CCNH) or resistance (DNAJB11 and PARP1). Our study identified a new gene signature that significantly predicts patients with higher probability to respond to treatment with trabectedin. Targeting some genes of this signature emerges as a potential strategy to enhance trabectedin efficacy.

引用

页码：3691 / 3705

页数：15

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PLOS ONE, 2013, 8 (12)

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