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Prognostic value of IL-27 polymorphisms and the susceptibility to epithelial ovarian cancer in a Chinese population

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Abstract

This study investigated the association between IL-27 gene polymorphisms and susceptibility to epithelial ovarian cancer in a Chinese population and discusses the risk factors associated with survival time. We collected data on 229 patients diagnosed with epithelial ovarian cancer, from 15 to 77 years of age with a long clinical follow-up period. Polymerase chain reaction-restriction fragment length polymorphism was performed to determine the genotype of IL-27 gene polymorphisms. Ovarian cancer-specific survival (OCSS) according to genotype of IL-27 gene polymorphisms was explored by Kaplan–Meier analysis and Cox proportional hazards modeling. Significant differences for genotype frequencies of both SNP sites were found between cases and controls. Both allele G frequencies were significantly greater among the cases (rs153109: 0.404 vs. 0.303, P = 0.001, odds ratio [OR] = 1.333, 95% confidence interval [CI] = 1.133–1.567; rs17855750: 0.146 vs. 0.083, P = 0.001, OR = 1.766, 95% CI = 1.258–2.481). Haplotype analysis showed haplotypes AG, GT and GG were associated with increased ovarian cancer susceptibility while AT was a protective haplotype. Advanced FIGO stage (stages III + IV) and non-optimal cytoreductive surgery (residual tumor ≥1 cm) were poor prognostic factors in the univariate analysis (P = 0.003, P = 0.049). However, FIGO stage was found to be the only independent significant prognostic factor by Cox proportional hazards analysis (P = 0.042). IL-27p28 mRNA expression was significantly decreased in ovarian cancer patients (P < 0.0001), while no significant relationship was found between IL-27p28 mRNA expression and polymorphism of rs153109 and rs17855750 (P = 0.193 and P = 0.146, respectively). Our study suggests that IL-27 gene polymorphisms may be involved in the susceptibility to epithelial ovarian cancer, but not in survival in a clinic-based Chinese population. Haplotype analysis of these two SNPs seems to be an important mark to predict the disease susceptibility. Advanced FIGO stage, as the only significant, independent risk factor, predicts poor clinical outcomes for patients diagnosed with epithelial ovarian cancer. The decreased expression of IL-27p28 mRNA in ovarian cancer might indicate the antitumor activities of this novel cytokine.

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References

  • Burger RA, Sill MW, Monk BJ, Greer BE, Sorosky JI (2007) Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group Study. Journal of clinical oncology 25(33):5165–5171. doi:10.1200/JCO.2007.11.5345

    Article  CAS  PubMed  Google Scholar 

  • Chae SC, Li CS, Kim KM, Yang JY, Zhang Q, Lee YC, Yang YS, Chung HT (2007) Identification of polymorphisms in human interleukin-27 and their association with asthma in a Korean population. Journal of human genetics 52(4):355–361. doi:10.1007/s10038-007-0123-8

    Article  CAS  PubMed  Google Scholar 

  • Chen Q, Ghilardi N, Wang H, Baker T, Xie MH, Gurney A, Grewal IS, de Sauvage FJ (2000) Development of Th1-type immune responses requires the type I cytokine receptor TCCR. Nature 407(6806):916–920. doi:10.1038/35038103

    Article  CAS  PubMed  Google Scholar 

  • Chiyo M, Shimozato O, Yu L, Kawamura K, Iizasa T, Fujisawa T, Tagawa M (2005) Expression of IL-27 in murine carcinoma cells produces antitumor effects and induces protective immunity in inoculated host animals. International journal of cancer Journal international du cancer 115(3):437–442. doi:10.1002/ijc.20848

    Article  CAS  PubMed  Google Scholar 

  • Cocco C, Di Carlo E, Zupo S, Canale S, Zorzoli A, Ribatti D, Morandi F, Ognio E, Airoldi I (2012) Complementary IL-23 and IL-27 anti-tumor activities cause strong inhibition of human follicular and diffuse large B-cell lymphoma growth in vivo. Leukemia 26(6):1365–1374. doi:10.1038/leu.2011.363

    Article  CAS  PubMed  Google Scholar 

  • Devergne O, Hummel M, Koeppen H, Le Beau MM, Nathanson EC, Kieff E, Birkenbach M (1996) A novel interleukin-12 p40-related protein induced by latent Epstein–Barr virus infection in B lymphocytes. Journal of virology 70(2):1143–1153

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fishman D, Faulds G, Jeffery R, Mohamed-Ali V, Yudkin JS, Humphries S, Woo P (1998) The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. The Journal of clinical investigation 102(7):1369–1376. doi:10.1172/JCI2629

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hisada M, Kamiya S, Fujita K, Belladonna ML, Aoki T, Koyanagi Y, Mizuguchi J, Yoshimoto T (2004) Potent antitumor activity of interleukin-27. Cancer research 64(3):1152–1156

    Article  CAS  PubMed  Google Scholar 

  • Hu P, Hu HD, Chen M, Peng ML, Tang L, Tang KF, Matsui M, Belladonna ML, Yoshimoto T, Zhang DZ, Xiang R, Ren H (2009) Expression of interleukins-23 and 27 leads to successful gene therapy of hepatocellular carcinoma. Molecular immunology 46(8–9):1654–1662. doi:10.1016/j.molimm.2009.02.025

    Article  CAS  PubMed  Google Scholar 

  • Huang N, Liu L, Wang XZ, Liu D, Yin SY, Yang XD (2008) Association of interleukin (IL)-12 and IL-27 gene polymorphisms with chronic obstructive pulmonary disease in a Chinese population. DNA and cell biology 27(9):527–531. doi:10.1089/dna.2007.0715

    Article  CAS  PubMed  Google Scholar 

  • Huang ZQ, Wang JL, Pan GG, Wei YS (2012) Association of single nucleotide polymorphisms in IL-12 and IL-27 genes with colorectal cancer risk. Clinical biochemistry 45(1–2):54–59. doi:10.1016/j.clinbiochem.2011.10.004

    Article  CAS  PubMed  Google Scholar 

  • Katsumata N, Yasuda M, Takahashi F, Isonishi S, Jobo T, Aoki D, Tsuda H, Sugiyama T, Kodama S, Kimura E, Ochiai K, Noda K (2009) Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: a phase 3, open-label, randomised controlled trial. Lancet 374(9698):1331–1338. doi:10.1016/S0140-6736(09)61157-0

    Article  CAS  PubMed  Google Scholar 

  • Li CS, Zhang Q, Lee KJ, Cho SW, Lee KM, Hahm KB, Choi SC, Yun KJ, Chung HT, Chae SC (2009) Interleukin-27 polymorphisms are associated with inflammatory bowel diseases in a Korean population. Journal of gastroenterology and hepatology 24(10):1692–1696. doi:10.1111/j.1440-1746.2009.05901.x

    Article  CAS  PubMed  Google Scholar 

  • Li Y, Kang S, Qin JJ, Wang N, Zhou RM, Sun HY (2012) nm23 gene polymorphisms are associated with survival of patients with epithelial ovarian cancer but not with susceptibility to disease. Gynecologic oncology 126(3):455–459. doi:10.1016/j.ygyno.2012.06.004

    Article  CAS  PubMed  Google Scholar 

  • Lucas S, Ghilardi N, Li J, de Sauvage FJ (2003) IL-27 regulates IL-12 responsiveness of naive CD4+ T cells through Stat1-dependent and -independent mechanisms. Proc Natl Acad Sci U S A 100(25):15047–15052. doi:10.1073/pnas.2536517100

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Marks JR, Davidoff AM, Kerns BJ, Humphrey PA, Pence JC, Dodge RK, Clarke-Pearson DL, Iglehart JD, Bast RC Jr, Berchuck A (1991) Overexpression and mutation of p53 in epithelial ovarian cancer. Cancer research 51(11):2979–2984

    CAS  PubMed  Google Scholar 

  • Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W et al (1994) A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266(5182):66–71

    Article  CAS  PubMed  Google Scholar 

  • Oniki S, Nagai H, Horikawa T, Furukawa J, Belladonna ML, Yoshimoto T, Hara I, Nishigori C (2006) Interleukin-23 and interleukin-27 exert quite different antitumor and vaccine effects on poorly immunogenic melanoma. Cancer research 66(12):6395–6404. doi:10.1158/0008-5472.CAN-05-4087

    Article  CAS  PubMed  Google Scholar 

  • Pflanz S, Timans JC, Cheung J, Rosales R, Kanzler H, Gilbert J, Hibbert L, Churakova T, Travis M, Vaisberg E, Blumenschein WM, Mattson JD, Wagner JL, To W, Zurawski S, McClanahan TK, Gorman DM, Bazan JF, de Waal MR, Rennick D, Kastelein RA (2002) IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4(+) T cells. Immunity 16(6):779–790

    Article  CAS  PubMed  Google Scholar 

  • Pflanz S, Hibbert L, Mattson J, Rosales R, Vaisberg E, Bazan JF, Phillips JH, McClanahan TK, de Waal MR, Kastelein RA (2004) WSX-1 and glycoprotein 130 constitute a signal-transducing receptor for IL-27. J Immunol 172(4):2225–2231

    CAS  PubMed  Google Scholar 

  • Salcedo R, Stauffer JK, Lincoln E, Back TC, Hixon JA, Hahn C, Shafer-Weaver K, Malyguine A, Kastelein R, Wigginton JM (2004) IL-27 mediates complete regression of orthotopic primary and metastatic murine neuroblastoma tumors: role for CD8+ T cells. J Immunol 173(12):7170–7182

    CAS  PubMed  Google Scholar 

  • Shimizu M, Shimamura M, Owaki T, Asakawa M, Fujita K, Kudo M, Iwakura Y, Takeda Y, Luster AD, Mizuguchi J, Yoshimoto T (2006) Antiangiogenic and antitumor activities of IL-27. J Immunol 176(12):7317–7324

    CAS  PubMed  Google Scholar 

  • Siegel R, Naishadham D, Jemal A (2013) Cancer statistics, 2013. CA: a cancer journal for clinicians 63(1):11–30. doi:10.3322/caac.21166

    Google Scholar 

  • Smith AJ, Humphries SE (2009) Cytokine and cytokine receptor gene polymorphisms and their functionality. Cytokine & growth factor reviews 20(1):43–59. doi:10.1016/j.cytogfr.2008.11.006

    Article  CAS  Google Scholar 

  • Smith AJ, D’Aiuto F, Palmen J, Cooper JA, Samuel J, Thompson S, Sanders J, Donos N, Nibali L, Brull D, Woo P, Humphries SE (2008) Association of serum interleukin-6 concentration with a functional IL6–6331T > C polymorphism. Clinical chemistry 54(5):841–850. doi:10.1373/clinchem.2007.098608

    Article  CAS  PubMed  Google Scholar 

  • Sprecher CA, Grant FJ, Baumgartner JW, Presnell SR, Schrader SK, Yamagiwa T, Whitmore TE, O’Hara PJ, Foster DF (1998) Cloning and characterization of a novel class I cytokine receptor. Biochemical and biophysical research communications 246(1):82–90. doi:10.1006/bbrc.1998.8576

    Article  CAS  PubMed  Google Scholar 

  • Takeda A, Hamano S, Yamanaka A, Hanada T, Ishibashi T, Mak TW, Yoshimura A, Yoshida H (2003) Cutting edge: role of IL-27/WSX-1 signaling for induction of T-bet through activation of STAT1 during initial Th1 commitment. J Immunol 170(10):4886–4890

    CAS  PubMed  Google Scholar 

  • Tao YP, Wang WL, Li SY, Zhang J, Shi QZ, Zhao F, Zhao BS (2012) Associations between polymorphisms in IL-12A, IL-12B, IL-12Rbeta1, IL-27 gene and serum levels of IL-12p40, IL-27p28 with esophageal cancer. Journal of cancer research and clinical oncology 138(11):1891–1900. doi:10.1007/s00432-012-1269-0

    Article  CAS  PubMed  Google Scholar 

  • Terry CF, Loukaci V, Green FR (2000) Cooperative influence of genetic polymorphisms on interleukin 6 transcriptional regulation. The Journal of biological chemistry 275(24):18138–18144. doi:10.1074/jbc.M000379200

    Article  CAS  PubMed  Google Scholar 

  • Tingulstad S, Skjeldestad FE, Halvorsen TB, Hagen B (2003) Survival and prognostic factors in patients with ovarian cancer. Obstetrics and gynecology 101(5 Pt 1):885–891

    Article  PubMed  Google Scholar 

  • Villarino A, Hibbert L, Lieberman L, Wilson E, Mak T, Yoshida H, Kastelein RA, Saris C, Hunter CA (2003) The IL-27R (WSX-1) is required to suppress T cell hyperactivity during infection. Immunity 19(5):645–655

    Article  CAS  PubMed  Google Scholar 

  • Wang M, Zhu XY, Wang L, Lin Y (2013) The -607C/A polymorphisms in interleukin-18 gene promoter contributes to cancer risk: evidence from a meta-analysis of 22 case-control studies. PloS one 8(10):e76915. doi:10.1371/journal.pone.0076915

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wei YS, Lan Y, Luo B, Lu D, Nong HB (2009) Association of variants in the interleukin-27 and interleukin-12 gene with nasopharyngeal carcinoma. Molecular carcinogenesis 48(8):751–757. doi:10.1002/mc.20522

    Article  CAS  PubMed  Google Scholar 

  • Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, Collins N, Gregory S, Gumbs C, Micklem G (1995) Identification of the breast cancer susceptibility gene BRCA2. Nature 378(6559):789–792. doi:10.1038/378789a0

    Article  CAS  PubMed  Google Scholar 

  • Yoshimoto T, Morishima N, Mizoguchi I, Shimizu M, Nagai H, Oniki S, Oka M, Nishigori C, Mizuguchi J (2008) Antiproliferative activity of IL-27 on melanoma. J Immunol 180(10):6527–6535

    CAS  PubMed  Google Scholar 

  • Zhang Z, Zhou B, Zhang J, Chen Y, Lai T, Yan L, Liang A, Li Y, Wang Y, Zhang L, Xi MR (2010) Association of interleukin-23 receptor gene polymorphisms with risk of ovarian cancer. Cancer genetics and cytogenetics 196(2):146–152. doi:10.1016/j.cancergencyto.2009.09.006

    Article  CAS  PubMed  Google Scholar 

  • Zhao B, Meng LQ, Huang HN, Pan Y, Xu QQ (2009) A novel functional polymorphism, 16974 A/C, in the interleukin-12-3′ untranslated region is associated with risk of glioma. DNA and cell biology 28(7):335–341. doi:10.1089/dna.2008.0845

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This study was supported by The National Natural Science Foundation grants of China [No. 81172494].

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The authors have no conflicts of interest.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, West China Second Hospital, Sichuan University, Number 20, 3rd section, South Renmin Road, Chengdu, Sichuan, 610041, China

    Zhu Zhang, Bin Zhou, Yuke Wu, Qianqian Gao, Yaping Song, Lin Zhang & Mingrong Xi

  2. Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, Sichuan, China

    Zhu Zhang & Mingrong Xi

  3. Laboratory of Molecular Translational Medicine, West China Institute of Women and Children’s Health, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China

    Bin Zhou, Yaping Song & Lin Zhang

  4. Department of Forensic Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Number 20, 3rd section, South Renmin Road, Chengdu, Sichuan, 610041, China

    Kui Zhang

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  1. Zhu Zhang
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Correspondence to Lin Zhang or Mingrong Xi.

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Zhu Zhang and Bin Zhou, contributed equally to the work and each is considered first author.

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Zhang, Z., Zhou, B., Wu, Y. et al. Prognostic value of IL-27 polymorphisms and the susceptibility to epithelial ovarian cancer in a Chinese population. Immunogenetics 66, 85–92 (2014). https://doi.org/10.1007/s00251-013-0753-2

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