A TGF-ß 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-ß 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 < 0.0001). The same trend was observed also for PFS (median PFS 0-2 UGs = 21.5, 3-4 UGs = 17.3 and 5-7 UGs = 11 months, p < 0.0001) and PFI (median PFI 0-2 UGs = 16.6, 3-4 UGs = 9.8 and 5-7 UGs = 3.8 months, p < 0.0001). The score was validated by permutation analysis. CONCLUSIONS: The proposed TGF-ß pathway score could be useful to define prognosis and platinum sensitivity of advanced EOC patients.