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

descriptionPublicationkeyboard_double_arrow_right Article 30 Jun 2021 Spain English Publisher:WileyJournal:Molecular Oncology, volume 15, pages 3,691-3,705 (issn: 1574-7891, eissn: 1878-0261,

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Authors: David S. Moura; Maria Peña‐Chilet; Juan Antonio Cordero Varela; Ramiro Alvarez‐Alegret; Carolina Agra‐Pujol; Francisco Izquierdo; Rafael Ramos; +23 Authors

doi: 10.1002/1878-0261.12996

pmid: 33983674

pmc: PMC8637557

handle: 10261/269160 , 11351/6693 , 20.500.13003/19404 , 10668/17787

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

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Abstract

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.

Country

Spain

Related Organizations

Hebron University
Palestinian-administered areas
Autonomous University of Barcelona
Spain
University of Seville
Spain
Complutense University of Madrid
Spain
University of Leon
Spain

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Keywords

ADN - Reparació, DNA Repair, Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia, Trabectedina, Estudios Retrospectivos, Dioxoles, gene signature, ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias de tejido conjuntivo y de tejidos blandos::sarcoma, predictive biomarkers, Predictive biomarkers, Recombinación homóloga, Tetrahydroisoquinolines, PHENOMENA AND PROCESSES::Chemical Phenomena::Biochemical Phenomena::DNA Repair, Gene signature, Humans, Sarcoma - Tractament, Antineoplastic Agents, Alkylating, RC254-282, Research Articles, Retrospective Studies, Other subheadings::Other subheadings::Other subheadings::/drug therapy, ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome, Perfilación de la expresión génica, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Sarcoma, Antineoplásicos Alquilantes, Neoplasias, Tetrahidroisoquinolinas, Humanos, DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Connective and Soft Tissue::Sarcoma, TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento, Daño del ADN, FENÓMENOS Y PROCESOS::fenómenos químicos::fenómenos bioquímicos::reparación del ADN, Eficacia, Reparación del ADN, trabectedin, Avaluació de resultats (Assistència sanitària), Pacientes, Supervivencia sin progresión, gene signature, predictive biomarkers, trabectedin, DNA Damage, Trabectedin

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