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Circulating microRNA-182 in plasma and its potential diagnostic and prognostic value for pancreatic cancer

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Abstract

MicroRNA-182 (miR-182) is overexpressed in several tumors and is found to be associated with adverse clinical characteristics. However, less information on the circulating miR-182 in pancreatic cancer (PCa) is available. The aim of this study was to detect the circulating miR-182 in plasma and to explore its potential diagnostic and prognostic value in PCa. Real-time quantitative PCR was employed to detect circulating miR-182 from 109 PCa and 38 chronic pancreatitis (CP) as well as 50 healthy controls. Our findings revealed that the level of circulating miR-182 in PCa patients was higher than that in CP patients and healthy controls (both at P < 0.05), which was significantly associated with clinical stages (P < 0.001) and lymph node metastasis (P = 0.018). The area under the receiver operating characteristic curve was 0.775, and the optimal cutoff value was 1.63, thus providing a sensitivity of 64.1 % and a specificity of 82.6 %. The diagnosis capability of circulating miR-182 was significantly higher than that of CA19-9, and the combination of two molecules had higher diagnosis capacity (sensitivity of 84.68 % and specificity of 86.77 %). Kaplan–Meier analysis demonstrated that the elevated circulating miR-182 was closely correlated with both shorten overall survival (OS) (P < 0.001) and disease-free survival (DFS) (P < 0.001). Cox analysis indicated that it was an independent prognostic factor for OS and DFS. Our data suggest that circulating miR-182 may be a potential and useful noninvasive tumor marker for diagnosis and prognosis of pancreatic cancer.

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References

  1. Li A, Yu J, Kim H, Wolfgang CL, Canto MI, Hruban RH, et al. MicroRNA array analysis finds elevated serum miR-1290 accurately distinguishes patients with low-stage pancreatic cancer from healthy and disease controls. Clin Cancer Res. 2013;19(13):3600–10.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  2. Satake K, Kanazawa G, Kho I, Chung YS, Umeyama K. A clinical evaluation of carbohydrate antigen 19-9 and carcinoembryonic antigen in patients with pancreatic carcinoma. J Surg Oncol. 1985;29(1):15–21.

    Article  PubMed  CAS  Google Scholar 

  3. Ganepola GA, Rutledge JR, Suman P, Yiengpruksawan A, Chang DH. Novel blood-based microRNA biomarker panel for early diagnosis of pancreatic cancer. World J Gastrointest Oncol. 2014;6(1):22–33.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281–97.

    Article  PubMed  CAS  Google Scholar 

  5. He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev. 2004;5(7):522–31.

    Article  CAS  Google Scholar 

  6. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA. 2008;105(30):10513–8.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  7. Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008;18(10):997–1006.

    Article  PubMed  CAS  Google Scholar 

  8. Ng EK, Chong WW, Jin H, Lam EK, Shin VY, Yu J, et al. Differential expression of microRNAs in plasma of patients with colorectal cancer: a potential marker for colorectal cancer screening. Gut. 2009;58(10):1375–81.

    Article  PubMed  CAS  Google Scholar 

  9. Selth LA, Townley SL, Bert AG, Stricker PD, Sutherland PD, Horvath LG, et al. Circulating microRNAs predict biochemical recurrence in prostate cancer patients. Br J Cancer. 2013;109(3):641–50.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  10. McDermott AM, Miller N, Wall D, Martyn LM, Ball G, Sweeney KJ, et al. Identification and validation of oncologic miRNA biomarkers for luminal A-like breast cancer. PLoS One. 2014;9(1):e87032.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Zhu C, Ren C, Han J, Ding Y, Du J, Dai N, et al. A five-microRNA panel in plasma was identified as potential biomarker for early detection of gastric cancer. Br J Cancer. 2014;110(9):2291–9.

    Article  PubMed  CAS  Google Scholar 

  12. Wang WS, Liu LX, Li GP, Chen Y, Li CY, Jin DY, et al. Combined serum CA19-9 and miR-27a-3p in peripheral blood mononuclear cells to diagnose pancreatic cancer. Cancer Prev Res (Phila). 2013;6(4):331–8.

    Article  CAS  Google Scholar 

  13. Liu J, Gao J, Du Y, Li Z, Ren Y, Gu J, et al. Combination of plasma microRNAs with serum CA19-9 for early detection of pancreatic cancer. Int J Cancer. 2012;131(3):683–91.

    Article  PubMed  CAS  Google Scholar 

  14. Morimura R, Komatsu S, Ichikawa D, Takeshita H, Tsujiura M, Nagata H, et al. Novel diagnostic value of circulating miR-18a in plasma of patients with pancreatic cancer. Br J Cancer. 2011;105(11):1733–40.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  15. Kawaguchi T, Komatsu S, Ichikawa D, Morimura R, Tsujiura M, Konishi H, et al. Clinical impact of circulating miR-221 in plasma of patients with pancreatic cancer. Br J Cancer. 2013;108(2):361–9.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  16. Liu Z, Liu J, Segura MF, Shao C, Lee P, Gong Y, et al. MiR-182 overexpression in tumourigenesis of high-grade serous ovarian carcinoma. J Pathol. 2012;228(2):204–15.

    Article  PubMed  CAS  Google Scholar 

  17. Lei R, Tang J, Zhuang X, Deng R, Li G, Yu J, et al. Suppression of MIM by microRNA-182 activates RhoA and promotes breast cancer metastasis. Oncogene. 2014;33(10):1287–96.

    Article  PubMed  CAS  Google Scholar 

  18. Segura MF, Hanniford D, Menendez S, Reavie L, Zou X, Alvarez-Diaz S, et al. Aberrant miR-182 expression promotes melanoma metastasis by repressing FOXO3 and microphthalmia-associated transcription factor. Proc Natl Acad Sci USA. 2009;106(6):1814–9.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  19. Yu J, Li A, Hong SM, Hruban RH, Goggins M. MicroRNA alterations of pancreatic intraepithelial neoplasias. Clin Cancer Res. 2012;18(4):981–92.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Li C, Du X, Tai S, Zhong X, Wang Z, Hu Z, et al. GPC1 regulated by miR-96-5p, rather than miR-182-5p, in inhibition of pancreatic carcinoma cell proliferation. Int J Mol Sci. 2014;15(4):6314–27.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Wang PY, Gong HT, Li BF, Lv CL, Wang HT, Zhou HH, et al. Higher expression of circulating miR-182 as a novel biomarker for breast cancer. Oncology letters. 2013;6(6):1681–6.

    PubMed  CAS  PubMed Central  Google Scholar 

  22. Scheffer AR, Holdenrieder S, Kristiansen G, von Ruecker A, Muller SC, Ellinger J. Circulating microRNAs in serum: novel biomarkers for patients with bladder cancer? World J Urol. 2014;32(2):353–8.

    Article  PubMed  CAS  Google Scholar 

  23. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods (San Diego, California). 2001;25(4):402–8.

    Article  CAS  Google Scholar 

  24. Ng EK, Li R, Shin VY, Jin HC, Leung CP, Ma ES, et al. Circulating microRNAs as specific biomarkers for breast cancer detection. PLoS One. 2013;8(1):e53141.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  25. Yu S, Liu Y, Wang J, Guo Z, Zhang Q, Yu F, et al. Circulating microRNA profiles as potential biomarkers for diagnosis of papillary thyroid carcinoma. J Clin Endocrinol Metab. 2012;97(6):2084–92.

    Article  PubMed  CAS  Google Scholar 

  26. Koopmann J, Buckhaults P, Brown DA, Zahurak ML, Sato N, Fukushima N, et al. Serum macrophage inhibitory cytokine 1 as a marker of pancreatic and other periampullary cancers. Clin Cancer Res. 2004;10(7):2386–92.

    Article  PubMed  CAS  Google Scholar 

  27. Matsubayashi H, Canto M, Sato N, Klein A, Abe T, Yamashita K, et al. DNA methylation alterations in the pancreatic juice of patients with suspected pancreatic disease. Cancer Res. 2006;66(2):1208–17.

    Article  PubMed  CAS  Google Scholar 

  28. Schmiegel WH, Kreiker C, Eberl W, Arndt R, Classen M, Greten H, et al. Monoclonal antibody defines CA 19-9 in pancreatic juices and sera. Gut. 1985;26(5):456–60.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  29. Hanke M, Hoefig K, Merz H, Feller AC, Kausch I, Jocham D, et al. A robust methodology to study urine microRNA as tumor marker: microRNA-126 and microRNA-182 are related to urinary bladder cancer. Urol Oncol. 2010;28(6):655–61.

    Article  PubMed  CAS  Google Scholar 

  30. Zheng D, Haddadin S, Wang Y, Gu LQ, Perry MC, Freter CE, et al. Plasma microRNAs as novel biomarkers for early detection of lung cancer. Int J Clin Exp Pathol. 2011;4(6):575–86.

    PubMed  CAS  PubMed Central  Google Scholar 

  31. Zhang GJ, Zhou T, Liu ZL, Tian HP, Xia SS. Plasma miR-200c and miR-18a as potential biomarkers for the detection of colorectal carcinoma. Mol Clin Oncol. 2013;1(2):379–84.

    PubMed  PubMed Central  Google Scholar 

  32. Taylor DD, Gercel-Taylor C. MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol. 2008;110(1):13–21.

    Article  PubMed  CAS  Google Scholar 

  33. Kong WQ, Bai R, Liu T, Cai CL, Liu M, Li X, et al. MicroRNA-182 targets cAMP-responsive element-binding protein 1 and suppresses cell growth in human gastric adenocarcinoma. FEBS J. 2012;279(7):1252–60.

    Article  PubMed  CAS  Google Scholar 

  34. Xu X, Dong Z, Li Y, Yang Y, Yuan Z, Qu X, et al. The upregulation of signal transducer and activator of transcription 5-dependent microRNA-182 and microRNA-96 promotes ovarian cancer cell proliferation by targeting forkhead box O3 upon leptin stimulation. Int J Biochem Cell Biol. 2013;45(3):536–45.

    Article  PubMed  CAS  Google Scholar 

  35. Qu Y, Li WC, Hellem MR, Rostad K, Popa M, McCormack E, et al. MiR-182 and miR-203 induce mesenchymal to epithelial transition and self-sufficiency of growth signals via repressing SNAI2 in prostate cells. Int J Cancer. 2013;133(3):544–55.

    Article  PubMed  CAS  Google Scholar 

  36. Xu X, Lu Z, Qiang W, Vidimar V, Kong B, Kim JJ, et al. Inactivation of AKT induces cellular senescence in uterine leiomyoma. Endocrinology. 2014;155(4):1510–9.

    Article  PubMed  Google Scholar 

  37. Li X, Luo F, Li Q, Xu M, Feng D, Zhang G, et al. Identification of new aberrantly expressed miRNAs in intestinal-type gastric cancer and its clinical significance. Oncol Rep. 2011;26(6):1431–9.

    PubMed  Google Scholar 

  38. Bansal P, Sonnenberg A. Pancreatitis is a risk factor for pancreatic cancer. Gastroenterology. 1995;109(1):247–51.

    Article  PubMed  CAS  Google Scholar 

  39. Hirata H, Ueno K, Shahryari V, Deng G, Tanaka Y, Tabatabai ZL, et al. MicroRNA-182-5p promotes cell invasion and proliferation by down regulating FOXF2, RECK and MTSS1 genes in human prostate cancer. PLoS One. 2013;8(1):e55502.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  40. Hui AB, Lin A, Xu W, Waldron L, Perez-Ordonez B, Weinreb I, et al. Potentially prognostic miRNAs in HPV-associated oropharyngeal carcinoma. Clin Cancer Res. 2013;19(8):2154–62.

    Article  PubMed  CAS  Google Scholar 

  41. Greither T, Grochola LF, Udelnow A, Lautenschlager C, Wurl P, Taubert H. Elevated expression of microRNAs 155, 203, 210 and 222 in pancreatic tumors is associated with poorer survival. Int J Cancer. 2010;126(1):73–80.

    Article  PubMed  CAS  Google Scholar 

  42. Dillhoff M, Liu J, Frankel W, Croce C, Bloomston M. MicroRNA-21 is overexpressed in pancreatic cancer and a potential predictor of survival. J Gastrointest Surg. 2008;12(12):2171–6.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Huynh C, Segura MF, Gaziel-Sovran A, Menendez S, Darvishian F, Chiriboga L, et al. Efficient in vivo microRNA targeting of liver metastasis. Oncogene. 2011;30(12):1481–8.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Lanju Yang or Yilei Xiao.

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Chen, Q., Yang, L., Xiao, Y. et al. Circulating microRNA-182 in plasma and its potential diagnostic and prognostic value for pancreatic cancer. Med Oncol 31, 225 (2014). https://doi.org/10.1007/s12032-014-0225-z

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  • DOI: https://doi.org/10.1007/s12032-014-0225-z

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