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Gynecol Oncol. 2020 Jan;156(1):233-242. doi: 10.1016/j.ygyno.2019.10.019. Epub 2019 Nov 9.

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

Author information

1
Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Via Franco Gallini 2, 33081 Aviano, Italy. Electronic address: sgagno@cro.it.
2
Department of Oncology - ASUI Udine University Hospital, Via Pozzuolo 330, 33100, Udine, Italy. Electronic address: polettoelena@libero.it.
3
Department of Medicine (DAME), University of Udine, Via Palladio 8, 33100, Udine, Italy; Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Via Franco Gallini 2, 33081, Aviano, Italy. Electronic address: michelebarto89@gmail.com.
4
Clinic of Rheumatology, Department of Medical Area, University Hospital "Santa Maria della Misericordia", Via Pozzuolo 330, 33100, Udine, Italy. Electronic address: luca.quartuccio@asuiud.sanita.fvg.it.
5
Department of Biology, University of Padova, Via Ugo Bassi 58/B, 35122, Padova, Italy. Electronic address: chiara.romualdi@unipd.it.
6
Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Via Franco Gallini 2, 33081 Aviano, Italy. Electronic address: mgarziera@cro.it.
7
Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Via Franco Gallini 2, 33081, Aviano, Italy. Electronic address: sscalone@cro.it.
8
Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Via Franco Gallini 2, 33081, Aviano, Italy. Electronic address: rsorio@cro.it.
9
Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Via Franco Gallini 2, 33081 Aviano, Italy. Electronic address: edreussi@cro.it.
10
Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Via Franco Gallini 2, 33081 Aviano, Italy. Electronic address: czanusso@cro.it.
11
Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Via Franco Gallini 2, 33081 Aviano, Italy. Electronic address: edemattia@cro.it.
12
Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Via Franco Gallini 2, 33081 Aviano, Italy. Electronic address: rroncato@cro.it.
13
Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Via Franco Gallini 2, 33081 Aviano, Italy. Electronic address: ececchin@cro.it.
14
Gynaecological Oncology Unit, Centro di Riferimento Oncologico (CRO) di Aviano, IRCCS, Via Franco Gallini 2, 33081, Aviano, Italy. Electronic address: ggiorda@cro.it.
15
Clinic of Rheumatology, Department of Medical Area, University Hospital "Santa Maria della Misericordia", Via Pozzuolo 330, 33100, Udine, Italy. Electronic address: salvatore.devita@asuiud.sanita.fvg.it.
16
Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Via Franco Gallini 2, 33081 Aviano, Italy. Electronic address: mdalbo@cro.it.
17
Department of Medicine (DAME), University of Udine, Via Palladio 8, 33100, Udine, Italy; Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Via Franco Gallini 2, 33081, Aviano, Italy. Electronic address: fabio.puglisi@cro.it.
18
Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Via Franco Gallini 2, 33081 Aviano, Italy. Electronic address: gtoffoli@cro.it.

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.

KEYWORDS:

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

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