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Circulating miR-200c Levels Significantly Predict Response to Chemotherapy and Prognosis of Patients Undergoing Neoadjuvant Chemotherapy for Esophageal Cancer

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

There is increasing evidence that microRNA expression in cancer tissue is useful for predicting the prognosis of patients with cancer. However, the relationship between the levels of circulating microRNAs and response to chemotherapy and prognosis remains unclear in esophageal cancer.

Methods

We measured the serum levels of miR-21, miR-145, miR-200c, and let-7c by quantitative RT-PCR in 64 patients with esophageal cancer who underwent neoadjuvant chemotherapy.

Results

The serum levels of miR-21, miR-145, miR-200c, and let-7c in esophageal cancer patients were significantly higher than those in healthy volunteers. High expression of miR-200c correlated significantly with poor response to chemotherapy (p = 0.0211). There was no significant relationship between chemosensitivity and the levels of miR-21, miR-145, and let-7c. High expression of miR-200c was associated with shortened progression-free survival (p = 0.0076), but there was no significant relationship between prognosis and the expression of miR-21, miR-145, and let-7c. Multivariate analysis identified miR-200c expression as the most valuable prognostic factor for patients with esophageal cancer who receive neoadjuvant chemotherapy.

Conclusions

The serum level of miR-200c can be useful for predicting the response to chemotherapy and the prognosis of patients with esophageal cancer who receive neoadjuvant chemotherapy.

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References

  1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.

    Article  PubMed  Google Scholar 

  2. Miyata H, Yamasaki M, Kurokawa Y, et al. Survival factors in patients with recurrence after curative resection of esophageal squamous cell carcinomas. Ann Surg Oncol. 2011;18:3353–61.

    Article  PubMed  Google Scholar 

  3. Miyata H, Yoshioka A, Yamasaki M, et al. Tumor budding in tumor invasive front predicts prognosis and survival of patients with esophageal squamous cell carcinomas receiving neoadjuvant chemotherapy. Cancer. 2009;115:3324–34.

    Article  PubMed  Google Scholar 

  4. Yamasaki M, Miyata H, Tanaka K, et al. Multicenter phase I/II study of docetaxel, cisplatin and fluorouracil combination chemotherapy in patients with advanced or recurrent squamous cell carcinoma of the esophagus. Oncology. 2011;80:307–13.

    Article  PubMed  CAS  Google Scholar 

  5. Yun T, Han JY, Lee JS, et al. Phase II study of weekly paclitaxel and capecitabine in patients with metastatic or recurrent esophageal squamous cell carcinoma. BMC Cancer. 2011;11:385.

    Article  PubMed  CAS  Google Scholar 

  6. Zhang J, Yang Y, Yang T, et al. MicroRNA-22, downregulated in hepatocellular carcinoma and correlated with prognosis, suppresses cell proliferation and tumourigenicity. Br J Cancer. 2010;103:1215–20.

    Article  PubMed  CAS  Google Scholar 

  7. Hamano R, Miyata H, Yamasaki M, et al. Overexpression of miR-200c induces chemoresistance in esophageal cancers mediated through activation of the Akt signaling pathway. Clin Cancer Res. 2011;17:3029–38.

    Article  PubMed  CAS  Google Scholar 

  8. Hamano R, Miyata H, Yamasaki M, et al. High expression of Lin28 is associated with tumour aggressiveness and poor prognosis of patients in oesophagus cancer. Br J Cancer. 2012;106:1415–23.

    Article  PubMed  CAS  Google Scholar 

  9. Liu N, Chen NY, Cui RX, et al. Prognostic value of a microRNA signature in nasopharyngeal carcinoma: a microRNA expression analysis. Lancet Oncol. 2012;13:633–41.

    Article  PubMed  CAS  Google Scholar 

  10. Gao G, Gay HA, Chernock RD, et al. A microRNA expression signature for the prognosis of oropharyngeal squamous cell carcinoma. Cancer. 2013;119:72–80.

    Article  PubMed  CAS  Google Scholar 

  11. Mitchell PS, Parkin RK, Kroh EM, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA. 2008;105:10513–8.

    Article  PubMed  CAS  Google Scholar 

  12. Asaga S, Kuo C, Nguyen T, Terpenning M, Giuliano AE, Hoon DS. Direct serum assay for microRNA-21 concentrations in early and advanced breast cancer. Clin Chem. 2011;57:84–91.

    Article  PubMed  CAS  Google Scholar 

  13. Tsujiura M, Ichikawa D, Komatsu S, et al. Circulating microRNAs in plasma of patients with gastric cancers. Br J Cancer. 2010;102:1174–9.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  15. Komatsu S, Ichikawa D, Takeshita H, et al. Circulating microRNAs in plasma of patients with oesophageal squamous cell carcinoma. Br J Cancer. 2011;105:104–11.

    Article  PubMed  CAS  Google Scholar 

  16. Konishi H, Ichikawa D, Komatsu S, et al. Detection of gastric cancer–associated microRNAs on microRNA microarray comparing pre- and post-operative plasma. Br J Cancer. 2012;106:740–7.

    Article  PubMed  CAS  Google Scholar 

  17. Tomimaru Y, Eguchi H, Nagano H, et al. Circulating microRNA-21 as a novel biomarker for hepatocellular carcinoma. J Hepatol. 2012;56:167–75.

    Article  PubMed  CAS  Google Scholar 

  18. Heegaard NH, Schetter AJ, Welsh JA, Yoneda M, Bowman ED, Harris CC. Circulating micro-RNA expression profiles in early stage non-small cell lung cancer. Int J Cancer. 2012;130:1378–86.

    Article  PubMed  CAS  Google Scholar 

  19. Sugimura K, Miyata H, Tanaka K, et al. Let-7 expression is a significant determinant of response to chemotherapy through the regulation of IL-6/STAT3 pathway in esophageal squamous cell carcinoma. Clin Cancer Res. 2012;18:5144–53.

    Article  PubMed  CAS  Google Scholar 

  20. Yano M, Takachi K, Doki Y, et al. Preoperative chemotherapy for clinically node-positive patients with squamous cell carcinoma of the esophagus. Dis Esophagus. 2006;19:158–63.

    Article  PubMed  CAS  Google Scholar 

  21. Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer. 1981;47:207–14.

    Article  PubMed  CAS  Google Scholar 

  22. Cortez MA, Calin GA. MicroRNA identification in plasma and serum: a new tool to diagnose and monitor diseases. Expert Opin Biol Ther. 2009;9:703–11.

    Article  PubMed  CAS  Google Scholar 

  23. Cheng H, Zhang L, Cogdell DE, et al. Circulating plasma MiR-141 is a novel biomarker for metastatic colon cancer and predicts poor prognosis. PLoS One. 2011;6:e17745.

    Article  PubMed  CAS  Google Scholar 

  24. Schmittgen TD, Jiang J, Liu Q, Yang L. A high-throughput method to monitor the expression of microRNA precursors. Nucleic Acids Res. 2004;32:e43.

    Article  PubMed  Google Scholar 

  25. Imanaka Y, Tsuchiya S, Sato F, Shimada Y, Shimizu K, Tsujimoto G. MicroRNA-141 confers resistance to cisplatin-induced apoptosis by targeting YAP1 in human esophageal squamous cell carcinoma. J Hum Genet. 2011;56:270–6.

    Article  PubMed  CAS  Google Scholar 

  26. Hummel R, Watson DI, Smith C, et al. Mir-148a improves response to chemotherapy in sensitive and resistant oesophageal adenocarcinoma and squamous cell carcinoma cells. J Gastrointest Surg. 2011;15:429–38.

    Article  PubMed  Google Scholar 

  27. Zhang H, Li M, Han Y, et al. Down-regulation of miR-27a might reverse multidrug resistance of esophageal squamous cell carcinoma. Dig Dis Sci. 2010;55:2545–51.

    Article  PubMed  CAS  Google Scholar 

  28. Arroyo JD, Chevillet JR, Kroh EM, et al. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci USA. 2011;108:5003–8.

    Article  PubMed  CAS  Google Scholar 

  29. Vickers KC, Palmisano BT, Shoucri BM, Shamburek RD, Remaley AT. MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat Cell Biol. 2011;13:423–33.

    Article  PubMed  CAS  Google Scholar 

  30. Hasselmann DO, Rappl G, Tilgen W, Reinhold U. Extracellular tyrosinase mRNA within apoptotic bodies is protected from degradation in human serum. Clin Chem. 2001;47:1488–9.

    PubMed  CAS  Google Scholar 

  31. Kosaka N, Iguchi H, Yoshioka Y, Takeshita F, Matsuki Y, Ochiya T. Secretory mechanisms and intercellular transfer of microRNAs in living cells. J Biol Chem. 2010;285:17442–52.

    Article  PubMed  CAS  Google Scholar 

  32. Kurashige J, Kamohara H, Watanabe M, et al. Serum microRNA-21 is a novel biomarker in patients with esophageal squamous cell carcinoma. J Surg Oncol. 2012;106:188–92.

    Article  PubMed  CAS  Google Scholar 

  33. Wei J, Gao W, Zhu CJ, et al. Identification of plasma microRNA-21 as a biomarker for early detection and chemosensitivity of non–small cell lung cancer. Chin J Cancer. 2011;30:407–14.

    Article  PubMed  CAS  Google Scholar 

  34. Zhang HL, Yang LF, Zhu Y, et al. Serum miRNA-21: elevated levels in patients with metastatic hormone-refractory prostate cancer and potential predictive factor for the efficacy of docetaxel-based chemotherapy. Prostate. 2011;71:326–31.

    Article  PubMed  CAS  Google Scholar 

  35. Wang H, Tan G, Dong L, et al. Circulating MiR-125b as a marker predicting chemoresistance in breast cancer. PLoS One. 2012;7:e34210.

    Article  PubMed  CAS  Google Scholar 

  36. Yu J, Ohuchida K, Mizumoto K, et al. MicroRNA, hsa-miR-200c, is an independent prognostic factor in pancreatic cancer and its upregulation inhibits pancreatic cancer invasion but increases cell proliferation. Mol Cancer. 2010;9:169.

    Article  PubMed  Google Scholar 

  37. Chen ML, Liang LS, Wang XK. miR-200c inhibits invasion and migration in human colon cancer cells SW480/620 by targeting ZEB1. Clin Exp Metastasis. 2012;29:457–69.

    Article  PubMed  CAS  Google Scholar 

  38. Adam L, Zhong M, Choi W, et al. miR-200 expression regulates epithelial-to-mesenchymal transition in bladder cancer cells and reverses resistance to epidermal growth factor receptor therapy. Clin Cancer Res. 2009;15:5060–72.

    Article  PubMed  CAS  Google Scholar 

  39. Chen J, Tian W, Cai H, He H, Deng Y. Down-regulation of microRNA-200c is associated with drug resistance in human breast cancer. Med Oncol. 2012;29:2527–34.

    Article  PubMed  CAS  Google Scholar 

  40. Puhr M, Hoefer J, Schafer G, et al. Epithelial-to-mesenchymal transition leads to docetaxel resistance in prostate cancer and is mediated by reduced expression of miR-200c and miR-205. Am J Pathol. 2012;181:2188–201.

    Article  PubMed  CAS  Google Scholar 

  41. Komatsu S, Ichikawa D, Takeshita H, et al. Prognostic impact of circulating miR-21 and miR-375 in plasma of patients with esophageal squamous cell carcinoma. Expert Opin Biol Ther. 2012;12:S53–9.

    Article  PubMed  CAS  Google Scholar 

  42. Liu XG, Zhu WY, Huang YY, et al. High expression of serum miR-21 and tumor miR-200c associated with poor prognosis in patients with lung cancer. Med Oncol. 2012;29:618–26.

    Article  PubMed  CAS  Google Scholar 

  43. Komatsu S, Ichikawa D, Tsujiura M, et al. Prognostic impact of circulating miR-21 in the plasma of patients with gastric carcinoma. Anticancer Res. 2013;33:271–6.

    PubMed  Google Scholar 

  44. Pigati L, Yaddanapudi SC, Iyengar R, et al. Selective release of microRNA species from normal and malignant mammary epithelial cells. PLoS One. 2010;5:e13515.

    Article  PubMed  Google Scholar 

  45. Ohshima K, Inoue K, Fujiwara A, et al. Let-7 microRNA family is selectively secreted into the extracellular environment via exosomes in a metastatic gastric cancer cell line. PLoS One. 2010;5:e13247.

    Article  PubMed  Google Scholar 

  46. Fabbri M, Paone A, Calore F, et al. MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response. Proc Natl Acad Sci USA. 2012;109:E2110–6.

    Article  PubMed  CAS  Google Scholar 

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The authors declare no conflict of interest.

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Correspondence to Hiroshi Miyata MD, PhD.

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Tanaka, K., Miyata, H., Yamasaki, M. et al. Circulating miR-200c Levels Significantly Predict Response to Chemotherapy and Prognosis of Patients Undergoing Neoadjuvant Chemotherapy for Esophageal Cancer. Ann Surg Oncol 20 (Suppl 3), 607–615 (2013). https://doi.org/10.1245/s10434-013-3093-4

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  • DOI: https://doi.org/10.1245/s10434-013-3093-4

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