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

Published:November 08, 2019DOI:https://doi.org/10.1016/j.ygyno.2019.10.019

      Highlights

      • Germ-line polymorphisms in immune system were significantly associated with the outcome of advanced ovarian cancer patients.
      • TGF-β signaling emerged as a pathway with a possible role in the definition of patient's prognosis and platinum-sensitivity.
      • The score based on unfavourable genotypes in TGF- β signaling was able to stratify patients according to PFI, PFS and OS.

      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 < 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-β pathway score could be useful to define prognosis and platinum sensitivity of advanced EOC patients.

      Graphical abstract

      Keywords

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