Circulating tumor cell free DNA genes as biomarker for platinum resistant ovarian cancer diagnosis

Clinical management of the most lethal gynecological cancer begins by optimal debulking with first-line platinum-based chemotherapy. However, in ~80% patients, ovarian cancer will recur and is thereafter typically lethal. Biomarker panels identifying platinum-resistance enables better stratification of patients for precision therapy. Serum retrospectively collected from poor (24 months PFI) prognosis patients were evaluated using circulating tumor cell free DNA (cfDNA). DNA from both groups showed 50 – 10,000 bp fragments. cfDNA sequencing and pairwise analysis showed that gene dosages varied: high (29 genes) and low (64 genes), among poor and favorable prognosis patients. Gene ontology analysis of higher dose genes predominantly grouped into cytoskeletal proteins; while lower dose genes, as hydrolases and receptors. Higher dosage genes searched for cancer-relatedness in Reactome database indicated 15 genes were referenced with cancer. Among them 3 genes, TGFBR2, ZMIZ2 and NRG2, were interacting with more than 4 cancer-associated genes. Protein expression analysis of tumor samples indicated that TGFBR2 was downregulated and ZMIZ2 was upregulated in poor prognosis patients. Thus, we propose serum cfDNA gene dosage in combination with their protein expression in tumor samples can be developed as biomarker panels for platinum-resistance determination amongst ovarian cancer patients.