A two-gene epigenetic signature for the prediction of response to neoadjuvant chemotherapy in triple-negative breast cancer patients

• DOI: 10.1186/s13148-019-0626-0
• Publication Date: 2019-02-20T07:23:59Z
• Authors: Begoña Pineda; Angel Diaz-Lagares; José Alejandro Pé...; Octavio Burgués; Inés González-Bar...; Ana B. Crujeiras; Juan Sandoval; Manel Esteller; Ana Lluch; Pilar Eroles
• Keywords: Triple-negative breast cancer; Gene signature

Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) varies between 30 and 40% approximately. To provide further insight into the prediction of pCR, we evaluated role an epigenetic methylation-based signature. Epigenetic assessment DNA extracted from biopsy archived samples previous to NAC TNBC patients was performed. Patients included were categorized according responder (pCR or residual burden, RCB = 0) non-responder (non-pCR > patients. A methyloma study performed a discovery cohort by Infinium HumanMethylation450 BeadChip (450K array) Illumina. The silencing those methylated genes validated bisulfite pyrosequencing (PyroMark Q96 System version 2.0.6, Qiagen) qRT-PCR independent TN cell lines. Twenty-four validation cohorts, respectively. In cohort, nine differentially methylated: six presented higher methylation (LOC641519, LEF1, HOXA5, EVC2, TLX3, CDKL2) three greater (FERD3L, CHL1, TRIP10). After validation, two-gene (FER3L TRIP10) score predicted 0 with area under ROC curve (AUC) 0.905 (95% CI 0.805–1.000). positive showed 78.6% versus only 10.7% if signature negative. These results suggest that pCR could be accurately FERD3L TRIP10 genes. Further prospective these findings is warranted.