Advertisement

Tumor Biology

, Volume 37, Issue 7, pp 9931–9942 | Cite as

MiR-608 rs4919510 is associated with prognosis of hepatocellular carcinoma

  • Xiao-Pin Ma
  • Guopeng Yu
  • Xubo Chen
  • Qianyi Xiao
  • Zhuqing Shi
  • Lu-Yao Zhang
  • Haitao Chen
  • Pengyin Zhang
  • Dong-Lin Ding
  • Hui-Xing Huang
  • Hexige Saiyin
  • Tao-Yang Chen
  • Pei-Xin Lu
  • Neng-Jin Wang
  • Hongjie Yu
  • Carly Conran
  • Jielin Sun
  • S. Lilly Zheng
  • Jianfeng Xu
  • Long Yu
  • De-Ke Jiang
Original Article

Abstract

Single nucleotide polymorphisms (SNPs) within microRNAs (miRNAs) are considered potential markers for risk and prognosis of various cancers. In the current study, we aimed to determine whether miR-608 rs4919510 affected hepatocellular carcinoma (HCC) prognosis. We genotyped rs4919510 using DNA from blood samples of 362 HCC patients receiving surgical resection of HCC tumor. Associations between rs4919510 and overall survival (OS) and demographic characteristics and clinical features were estimated using the Cox proportional hazards model. Results showed that HCC patients who carried the rs4919510 CC genotype had a significantly longer OS compared to those who carried the GG genotype (P = 0.013, hazard ratio [HR] = 0.600, 95 % confidence interval [CI] 0.402–0.897) and the CG + GG genotype (P = 0.033, HR = 0.681, 95 % CI 0.479–0.970) in univariate analysis. Similar results were obtained in multivariate analysis. Further stratification analysis indicated that rs4919510 was significantly associated with OS in patients who were satisfied with one of the following criteria: male gender, HbsAg-positive, α-fetoprotein (AFP)-positive, tumor size >5 cm, cirrhosis, solitary tumor, I + II pTNM stage, or no tumor capsule. Finally, a significantly higher frequency of rs4919510 CC genotype was observed in patients with cirrhosis (22.9 %, 55/240) than those without cirrhosis (14.0 %, 17/121) (P = 0.047). In conclusion, our results illustrated the potential role of miR-608 rs4919510 as a prognostic marker for HCC patients undergoing surgical resection of the tumor.

Keywords

Hepatocellular carcinoma Survival miRNA Genetic polymorphism 

Notes

Acknowledgments

We thank all the patients who agreed to participate in this study. The study is supported by the National Natural Science Foundation of China (31100895, and 81472618 [to D.-K.J.]), Outstanding Young Scholar Project of Fudan University (to D.-K.J.), as well as an intramural research grant for new young teachers from Fudan University (to D.-K.J.), an intramural research grant for promotion of the scientific research ability of young teachers from Fudan University (to D.-K.J.), an intramural research grant from Huashan Hospital, Fudan University (to J.X.), an intramural research grant from Fudan-VARI Center for Genetic Epidemiology, Fudan University (to J.X.)., the Research Fund of the State Key Laboratory of Genetic Engineering, Fudan University (to L.Y. and J.X.), and the Ellrodt-Schweighauser Family Chair of Cancer Genomic Research of NorthShore University HealthSystem (J. X.).

Compliance with ethical standards

Conflicts of interest

None

References

  1. 1.
    Yang JD, Roberts LR. Hepatocellular carcinoma: a global view. Nat Rev Gastroenterol Hepatol. 2010;7(8):448–58. doi: 10.1038/nrgastro.2010.100.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA: Cancer J Clin. 2015. doi: 10.3322/caac.21262.Google Scholar
  3. 3.
    Zhu AX. Molecularly targeted therapy for advanced hepatocellular carcinoma in 2012: current status and future perspectives. Semin Oncol. 2012;39(4):493–502. doi: 10.1053/j.seminoncol.2012.05.014.CrossRefPubMedGoogle Scholar
  4. 4.
    Schutte K, Schulz C, Link A, Malfertheiner P. Current biomarkers for hepatocellular carcinoma: surveillance, diagnosis and prediction of prognosis. World J Hepatol. 2015;7(2):139–49. doi: 10.4254/wjh.v7.i2.139.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Lee SC, Tan HT, Chung MC. Prognostic biomarkers for prediction of recurrence of hepatocellular carcinoma: current status and future prospects. World J Gastroenterol: WJG. 2014;20(12):3112–24. doi: 10.3748/wjg.v20.i12.3112.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Sala M, Forner A, Varela M, Bruix J. Prognostic prediction in patients with hepatocellular carcinoma. Semin Liver Dis. 2005;25(2):171–80. doi: 10.1055/s-2005-871197.CrossRefPubMedGoogle Scholar
  7. 7.
    Kong YW, Ferland-McCollough D, Jackson TJ, Bushell M. microRNAs in cancer management. Lancet Oncol. 2012;13(6):e249–58. doi: 10.1016/S1470-2045(12)70073-6.CrossRefPubMedGoogle Scholar
  8. 8.
    Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6(11):857–66. doi: 10.1038/nrc1997.CrossRefPubMedGoogle Scholar
  9. 9.
    Bartel B. MicroRNAs directing siRNA biogenesis. Nat Struct Mol Biol. 2005;12(7):569–71. doi: 10.1038/nsmb0705-569.CrossRefPubMedGoogle Scholar
  10. 10.
    Tao K, Yang J, Guo Z, Hu Y, Sheng H, Gao H, et al. Prognostic value of miR-221-3p, miR-342-3p and miR-491-5p expression in colon cancer. Am J Transl Res. 2014;6(4):391–401.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Tyagi N, Arora S, Deshmukh SK, Singh S, Marimuthu S, Singh AP. Exploiting nanotechnology for the development of MicroRNA-based cancer therapeutics. J Biomed Nanotechnol. 2016;12(1):28–42. doi: 10.1166/jbn.2016.2172.CrossRefPubMedGoogle Scholar
  12. 12.
    Duan R, Pak C, Jin P. Single nucleotide polymorphism associated with mature miR-125a alters the processing of pri-miRNA. Hum Mol Genet. 2007;16(9):1124–31. doi: 10.1093/hmg/ddm062.CrossRefPubMedGoogle Scholar
  13. 13.
    Wu C, Li M, Hu C, Duan H. Prognostic role of microRNA polymorphisms in patients with advanced esophageal squamous cell carcinoma receiving platinum-based chemotherapy. Cancer Chemother Pharmacol. 2014;73(2):335–41. doi: 10.1007/s00280-013-2364-x.CrossRefPubMedGoogle Scholar
  14. 14.
    Pardini B, Rosa F, Naccarati A, Vymetalkova V, Ye Y, Wu X, et al. Polymorphisms in microRNA genes as predictors of clinical outcomes in colorectal cancer patients. Carcinogenesis. 2015;36(1):82–6. doi: 10.1093/carcin/bgu224.CrossRefPubMedGoogle Scholar
  15. 15.
    Lin M, Gu J, Eng C, Ellis LM, Hildebrandt MA, Lin J, et al. Genetic polymorphisms in microRNA-related genes as predictors of clinical outcomes in colorectal adenocarcinoma patients. Clin Cancer Res: Off J Am Assoc Cancer Res. 2012;18(14):3982–91. doi: 10.1158/1078-0432.CCR-11-2951.CrossRefGoogle Scholar
  16. 16.
    Xu T, Zhu Y, Wei QK, Yuan Y, Zhou F, Ge YY, et al. A functional polymorphism in the miR-146a gene is associated with the risk for hepatocellular carcinoma. Carcinogenesis. 2008;29(11):2126–31. doi: 10.1093/carcin/bgn195.CrossRefPubMedGoogle Scholar
  17. 17.
    Wang R, Zhang J, Ma Y, Chen L, Guo S, Zhang X, et al. Association study of miR149 rs2292832 and miR608 rs4919510 and the risk of hepatocellular carcinoma in a large-scale population. Mol Med Rep. 2014;10(5):2736–44. doi: 10.3892/mmr.2014.2536.PubMedGoogle Scholar
  18. 18.
    Ryan BM, McClary AC, Valeri N, Robinson D, Paone A, Bowman ED, et al. rs4919510 in hsa-mir-608 is associated with outcome but not risk of colorectal cancer. PLoS ONE. 2012;7(5):e36306. doi: 10.1371/journal.pone.0036306.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Huang AJ, Yu KD, Li J, Fan L, Shao ZM. Polymorphism rs4919510:C > G in mature sequence of human microRNA-608 contributes to the risk of HER2-positive breast cancer but not other subtypes. PLoS ONE. 2012;7(5), e35252. doi: 10.1371/journal.pone.0035252.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Kupcinskas J, Wex T, Link A, Leja M, Bruzaite I, Steponaitiene R, et al. Gene polymorphisms of micrornas in Helicobacter pylori-induced high risk atrophic gastritis and gastric cancer. PLoS ONE. 2014;9(1), e87467. doi: 10.1371/journal.pone.0087467.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Yang PW, Huang YC, Hsieh CY, Hua KT, Huang YT, Chiang TH, et al. Association of miRNA-related genetic polymorphisms and prognosis in patients with esophageal squamous cell carcinoma. Ann Surg Oncol. 2014;21 Suppl 4:S601–9. doi: 10.1245/s10434-014-3709-3.CrossRefPubMedGoogle Scholar
  22. 22.
    Wei WJ, Wang YL, Li DS, Wang Y, Wang XF, Zhu YX, et al. Association study of single nucleotide polymorphisms in mature microRNAs and the risk of thyroid tumor in a Chinese population. Endocrine. 2015;49(2):436–44. doi: 10.1007/s12020-014-0467-8.CrossRefPubMedGoogle Scholar
  23. 23.
    Lee Y, Kim M, Han J, Yeom KH, Lee S, Baek SH, et al. MicroRNA genes are transcribed by RNA polymerase II. EMBO J. 2004;23(20):4051–60. doi: 10.1038/sj.emboj.7600385.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Ryan BM, Robles AI, Harris CC. Genetic variation in microRNA networks: the implications for cancer research. Nat Rev Cancer. 2010;10(6):389–402. doi: 10.1038/nrc2867.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Shen J, Ambrosone CB, DiCioccio RA, Odunsi K, Lele SB, Zhao H. A functional polymorphism in the miR-146a gene and age of familial breast/ovarian cancer diagnosis. Carcinogenesis. 2008;29(10):1963–6. doi: 10.1093/carcin/bgn172.CrossRefPubMedGoogle Scholar
  26. 26.
    Jazdzewski K, Murray EL, Franssila K, Jarzab B, Schoenberg DR, de la Chapelle A. Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma. Proc Natl Acad Sci U S A. 2008;105(20):7269–74. doi: 10.1073/pnas.0802682105.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Okubo M, Tahara T, Shibata T, Yamashita H, Nakamura M, Yoshioka D, et al. Association between common genetic variants in pre-microRNAs and gastric cancer risk in Japanese population. Helicobacter. 2010;15(6):524–31. doi: 10.1111/j.1523-5378.2010.00806.x.CrossRefPubMedGoogle Scholar
  28. 28.
    Xu B, Feng NH, Li PC, Tao J, Wu D, Zhang ZD, et al. A functional polymorphism in pre-miR-146a gene is associated with prostate cancer risk and mature miR-146a expression in vivo. Prostate. 2010;70(5):467–72. doi: 10.1002/pros.21080.PubMedGoogle Scholar
  29. 29.
    Hu Z, Chen J, Tian T, Zhou X, Gu H, Xu L, et al. Genetic variants of miRNA sequences and non-small cell lung cancer survival. J Clin Invest. 2008;118(7):2600–8. doi: 10.1172/JCI34934.PubMedPubMedCentralGoogle Scholar
  30. 30.
    Qiu F, Yang L, Zhang L, Yang X, Yang R, Fang W, et al. Polymorphism in mature microRNA-608 sequence is associated with an increased risk of nasopharyngeal carcinoma. Gene. 2015;565(2):180–6. doi: 10.1016/j.gene.2015.04.008.CrossRefPubMedGoogle Scholar
  31. 31.
    Xing J, Wan S, Zhou F, Qu F, Li B, Myers RE, et al. Genetic polymorphisms in pre-microRNA genes as prognostic markers of colorectal cancer. Cancer Epidemiol, Biomark Prev. 2012;21(1):217–27. doi: 10.1158/1055-9965.EPI-11-0624.CrossRefGoogle Scholar
  32. 32.
    Rah H, Kim HS, Cha SH, Kim YR, Lee WS, Ko JJ, et al. Association of breast cancer-related microRNA polymorphisms with idiopathic primary ovarian insufficiency. Menopause. 2015;22(4):437–43. doi: 10.1097/GME.0000000000000325.CrossRefPubMedGoogle Scholar
  33. 33.
    Zhang Y, Schiff D, Park D, Abounader R. MicroRNA-608 and microRNA-34a regulate chordoma malignancy by targeting EGFR, Bcl-xL and MET. PLoS ONE. 2014;9(3), e91546. doi: 10.1371/journal.pone.0091546.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Kang JG, Majerciak V, Uldrick TS, Wang X, Kruhlak M, Yarchoan R, et al. Kaposi’s sarcoma-associated herpesviral IL-6 and human IL-6 open reading frames contain miRNA binding sites and are subject to cellular miRNA regulation. J Pathol. 2011;225(3):378–89. doi: 10.1002/path.2962.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Tanaka T, Kishimoto T. The biology and medical implications of interleukin-6. Cancer Immunol Res. 2014;2(4):288–94. doi: 10.1158/2326-6066.CIR-14-0022.CrossRefPubMedGoogle Scholar
  36. 36.
    Jeyapalan Z, Deng Z, Shatseva T, Fang L, He C, Yang BB. Expression of CD44 3′-untranslated region regulates endogenous microRNA functions in tumorigenesis and angiogenesis. Nucleic Acids Res. 2011;39(8):3026–41. doi: 10.1093/nar/gkq1003.CrossRefPubMedGoogle Scholar
  37. 37.
    Rutnam ZJ, Yang BB. The non-coding 3′ UTR of CD44 induces metastasis by regulating extracellular matrix functions. J Cell Sci. 2012;125(Pt 8):2075–85. doi: 10.1242/jcs100818.CrossRefPubMedGoogle Scholar
  38. 38.
    Othman N, In LL, Harikrishna JA, Hasima N. Bcl-xL silencing induces alterations in hsa-miR-608 expression and subsequent cell death in A549 and SK-LU1 human lung adenocarcinoma cells. PLoS ONE. 2013;8(12), e81735. doi: 10.1371/journal.pone.0081735.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Johnson C, Han Y, Hughart N, McCarra J, Alpini G, Meng F. Interleukin-6 and its receptor, key players in hepatobiliary inflammation and cancer. Transl Gastrointest Cancer. 2012;1(1):58–70. doi: 10.3978/j.issn.2224-4778.2011.11.02.PubMedPubMedCentralGoogle Scholar
  40. 40.
    Liu Y, Fuchs J, Li C, Lin J. IL-6, a risk factor for hepatocellular carcinoma: FLLL32 inhibits IL-6-induced STAT3 phosphorylation in human hepatocellular cancer cells. Cell Cycle. 2010;9(17):3423–7.CrossRefPubMedGoogle Scholar
  41. 41.
    Wang Y, van Boxel-Dezaire AHH, Cheon H, Yang J, Stark GR. STAT3 activation in response to IL-6 is prolonged by the binding of IL-6 receptor to EGF receptor. Proc Natl Acad Sci U S A. 2013;110(42):16975–80. doi: 10.1073/pnas.1315862110.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Xiao-Pin Ma
    • 1
  • Guopeng Yu
    • 1
    • 2
    • 3
    • 4
    • 5
    • 6
    • 7
  • Xubo Chen
    • 1
  • Qianyi Xiao
    • 4
  • Zhuqing Shi
    • 1
    • 2
    • 3
    • 4
  • Lu-Yao Zhang
    • 1
  • Haitao Chen
    • 1
    • 2
    • 3
    • 4
  • Pengyin Zhang
    • 1
    • 2
    • 3
    • 4
  • Dong-Lin Ding
    • 1
  • Hui-Xing Huang
    • 1
  • Hexige Saiyin
    • 1
  • Tao-Yang Chen
    • 8
  • Pei-Xin Lu
    • 8
  • Neng-Jin Wang
    • 8
  • Hongjie Yu
    • 1
    • 2
    • 3
    • 4
  • Carly Conran
    • 9
  • Jielin Sun
    • 7
  • S. Lilly Zheng
    • 7
    • 9
  • Jianfeng Xu
    • 1
    • 2
    • 3
    • 4
    • 5
    • 9
  • Long Yu
    • 1
    • 10
  • De-Ke Jiang
    • 1
    • 2
    • 3
    • 4
    • 7
    • 9
    • 11
  1. 1.State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life SciencesFudan UniversityShanghaiChina
  2. 2.Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life SciencesFudan UniversityShanghaiChina
  3. 3.Center for genetic Epidemiology, School of Life SciencesFudan UniversityShanghaiChina
  4. 4.Center for Genetic Translational Medicine and Prevention, School of Public HealthFudan UniversityShanghaiChina
  5. 5.Fudan Institute of Urology, Huashan HospitalFudan UniversityShanghaiChina
  6. 6.Department of Urology, Xinhua Hospital, School of MedicineShanghai Jiaotong UniversityShanghaiChina
  7. 7.Center for Cancer GenomicsWake Forest University School of MedicineWinston-SalemUSA
  8. 8.Qidong Liver Cancer InstituteQidong People’s HospitalQidongChina
  9. 9.Center for Genomic Cancer ResearchNorthShore University HealthSystemEvanstonUSA
  10. 10.Institute of Biomedical ScienceFudan UniversityShanghaiChina
  11. 11.Pritzker School of MedicineUniversity of ChicagoChicagoUSA

Personalised recommendations