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

Background 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 the role of an epigenetic methylation-based signature. Methods Epigenetic assessment of DNA extracted from biopsy archived samples previous to NAC from TNBC patients was performed. Patients included were categorized according to previous response to NAC in responder (pCR or residual cancer burden, RCB = 0) or non-responder (non-pCR or RCB > 0) patients. A methyloma study was performed in a discovery cohort by the Infinium HumanMethylation450 BeadChip (450K arra…

Additional file 2: of A two-gene epigenetic signature for the prediction of response to neoadjuvant chemotherapy in triple-negative breast cancer patients

Thirty-five differentially methylated CpGs between responders and non-responders group selected from 450k array (delta value ≥ 0.2) corresponding to 23 genes located in promoter and island/shore (PPT 172 kb)

Additional file 3: of A two-gene epigenetic signature for the prediction of response to neoadjuvant chemotherapy in triple-negative breast cancer patients

Eleven differentially methylated CpGs, corresponding to 11 genes, showed significant methylation differences between non-responder and responder patients: 6 genes (LOC641518; LEF1; HOXA5; EVC2; CDKL2; TLX3) presented a methylation increase in non-responders group vs responders, and 5 genes (ZFHX4; LOC100192378; FERD3L; CHL1; TRIP10) decreased methylation level in non-responder patients compared to those who responded to NAC treatment (PPT 225 kb)

In the literature: April 2021

Additional file 1: of A two-gene epigenetic signature for the prediction of response to neoadjuvant chemotherapy in triple-negative breast cancer patients

List of all the biological processes enriched for the 71 differentially methylated genes between responder and non-responder patients according to the Gene Ontology analysis (DOCX 32 kb)

Additional file 5: of A two-gene epigenetic signature for the prediction of response to neoadjuvant chemotherapy in triple-negative breast cancer patients

Representation of the pathway interaction network of FERD3L and TRIP10 with other genes using Pathway Commons. FERD3L and TRIP10 are able to interact with different genes that have shown to be implicated in cancer drug resistance (PPT 452 kb)

Additional file 4: of A two-gene epigenetic signature for the prediction of response to neoadjuvant chemotherapy in triple-negative breast cancer patients

CpGs studied by pyrosequencing in the DC and in the VC to validate methylation in the candidate genes identified in the 450k array (Illumina). In bold, CpGs from 450k array. Normal type, consecutive CpGs (PPT 140 kb)

Additional file 6: of A two-gene epigenetic signature for the prediction of response to neoadjuvant chemotherapy in triple-negative breast cancer patients

Mean differences in methylation levels according to clinicopathological prognostic factors in both cohorts (DC+VC). cT, clinical tumor size; cN, clinical nodule affectation (PPTX 48 kb)

Additional file 8: of A two-gene epigenetic signature for the prediction of response to neoadjuvant chemotherapy in triple-negative breast cancer patients

Sequence of primers used by pyrosequencing in the validation assay of candidate genes obtained from 450k array (PPT 143 kb)

Additional file 7: of A two-gene epigenetic signature for the prediction of response to neoadjuvant chemotherapy in triple-negative breast cancer patients

Clinical inclusion and exclusion criteria followed to select TNBC patients for the methylation study (PPT 89 kb)