A TGF-β associated genetic score to define prognosis and platinum sensitivity in advanced epithelial ovarian cancer

Abstract Objective Epithelial ovarian cancer (EOC) is usually diagnosed at advanced stages with highly variable clinical outcomes, even among patients with similar clinical characteristics and treatments. Host immune system plays a pivotal role in EOC pathogenesis and progression. Here, we assessed the clinical significance of 192 single nucleotide polymorphisms (SNPs) on 34 immune-system related genes in EOC patients. Methods Two hundred and thirty advanced EOC patients treated with platinum-based chemotherapy were included. Germ-line DNA was analyzed with Illumina GoldenGate Genotyping Assay. Results Nineteen polymorphisms were significantly associated with overall survival (OS), 17 with progression free survival (PFS) and 20 with platinum-free interval (PFI). Of the 8 polymorphisms associated with all three outcomes, 7 SNPs belonged to genes involved in the TGF-β pathway. A genetic score was built considering the unfavourable genotypes (UGs) of these 7 polymorphisms (group 0–2 UGs: presence of 0, 1, or 2 UGs; group 3–4 UGs: 3 or 4 UGs; group 5–7: 5, 6, or 7 UGs). According to this score, OS decreased as the number of UGs increased (median OS: 0–2 UGs = not reached, 3–4 UGs = 44.6 and 5–7 UGs = 19.3 months, p  Conclusions The proposed TGF-β pathway score could be useful to define prognosis and platinum sensitivity of advanced EOC patients.