5-Hydroxymethylcytosine signals in serum are a predictor of chemoresistance in high-grade serous ovarian cancer

The genome-wide profiling of 5-hydroxymethylcytosine (5hmC) on circulating cell-free DNA (cfDNA) has revealed promising biomarkers for a variety of diseases. The purpose of our study is to investigate if 5hmC profiles from serum cfDNA are novel predictive biomarkers for the development of chemoresistance in high-grade serous ovarian cancer (HGSOC). We hypothesized that 5-hmC profiles associate with the development of chemoresistance and elucidate pathways that may drive chemoresistance in HGSOC. We developed a novel multivariate model based on clinico-pathologic data and a cfDNA-derived 5hmC-annotated gene that can predict response to platinum-based chemotherapy in intermediate-sensitive HGSOC. These results merit further investigation of our model as a predictive model. Patients diagnosed with HGSOC and with known platinum sensitivity status (Across all cohorts: sensitive n= 40, intermediate n= 34, resistant n= 37, and recurrent n= 20) were selected for this study. Nano-hmC-Seal was performed on cfDNA isolated from archived serum samples and differential 5hmC annotations were identified using DESeq2 to establish a model predictive of chemoresistance.