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

Sara Gagno, Elena Poletto, Michele Bartoletti, Luca Quartuccio, Chiara Romualdi, Marica Garziera, Simona Scalone, Roberto Sorio, Eva Dreussi, Chiara Zanusso, Elena De Mattia, Rossana Roncato, Erika Cecchin, Giorgio Giorda, Salvatore De Vita, Michele Dal Bo, Fabio Puglisi, Giuseppe Toffoli

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)233-242
Number of pages10
JournalGynecologic Oncology
Volume156
Issue number1
DOIs
Publication statusPublished - Jan 2020

Keywords

  • Immune system
  • Ovarian cancer
  • Platinum
  • Polymorphism
  • Survival
  • TGF-β

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynaecology

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