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
Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Tsujiura M, Ichikawa D, Komatsu S, et al. Circulating microRNAs in plasma of patients with gastric cancers. Br J Cancer. 2010;102:1174–9.
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.
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.
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.
Tomimaru Y, Eguchi H, Nagano H, et al. Circulating microRNA-21 as a novel biomarker for hepatocellular carcinoma. J Hepatol. 2012;56:167–75.
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.
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.
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.
Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer. 1981;47:207–14.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Wang H, Tan G, Dong L, et al. Circulating MiR-125b as a marker predicting chemoresistance in breast cancer. PLoS One. 2012;7:e34210.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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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