DNA methylation markers panel can improve prediction of response to neoadjuvant chemotherapy in luminal B breast cancer.

Scientific Reports
Vladimir O SiginAlexander S Tanas

Abstract

Despite the advantages of neoadjuvant chemotherapy (NACT), associated toxicity is a serious complication that renders monitoring of the patients' response to NACT highly important. Thus, prediction of tumor response to treatment is imperative to avoid exposure of potential non-responders to deleterious complications. We have performed genome-wide analysis of DNA methylation by XmaI-RRBS and selected CpG dinucleotides differential methylation of which discriminates luminal B breast cancer samples with different sensitivity to NACT. With this data, we have developed multiplex methylation sensitive restriction enzyme PCR (MSRE-PCR) protocol for determining the methylation status of 10 genes (SLC9A3, C1QL2, DPYS, IRF4, ADCY8, KCNQ2, TERT, SYNDIG1, SKOR2 and GRIK1) that distinguish BC samples with different NACT response. Analysis of these 10 markers by MSRE-PCR in biopsy samples allowed us to reveal three top informative combinations of markers, (1) IRF4 and C1QL2; (2) IRF4, C1QL2, and ADCY8; (3) IRF4, C1QL2, and DPYS, with the areas under ROC curves (AUCs) of 0.75, 0.78 and 0.74, respectively. A classifier based on IRF4 and C1QL2 better meets the diagnostic panel simplicity requirements, as it consists of only two markers. Diagnos...Continue Reading

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Citations

Feb 10, 2021·Journal of Molecular and Cellular Cardiology·Matthew A Fischer, Thomas M Vondriska
Jun 3, 2021·International Journal of Molecular Sciences·Francesco PettiniOttavia Spiga

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Datasets Mentioned

BETA
GSE144221

Methods Mentioned

BETA
biopsy
RRBS
PCR
biopsies
methylation profiling
methylation sequencing
electrophoresis
PCA

Software Mentioned

Bismark
Bowtie 2 aligner
R
Ion Torrent
cvAUC R package

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