Abstract
microRNA-133a (miR-133a) and miR-133b, located on chromosome 18 in the same bicistronic unit, have been commonly identified as being downregulated in esophageal squamous cell carcinoma (ESCC). The aim of this study was to investigate the correlation of miR-133a/b expression with efficacy of paclitaxel-based chemotherapy and clinical outcome of ESCC patients. miR-133a expression and miR-133b expression were examined in 100 newly diagnosed ESCC patients prior to treatment by quantitative real-time PCR. Then, the patients received four cycles of paclitaxel-based chemotherapy, the short-term treatment efficacy was evaluated, and a 3-year follow-up was performed. Expression levels of miR-133a and miR-133b were both significantly lower in ESCC tissues compared to adjacent noncancerous tissues (both P < 0.001). In addition, combined miR-133a/b downregulation was found to be closely correlated with advanced tumor stage (P = 0.02) and poor differentiation (P = 0.01). Moreover, the response rate of ESCC patients to paclitaxel-based chemotherapy was significantly higher in combined miR-133a/b downregulation group compared with other groups (P = 0.02). Furthermore, univariate and multivariate Cox analyses revealed that tumor stage and combined expression of miR-133a/b were independent prognosis factors in ESCC patients. Our data offer the convincing evidence that combined expression of miR-133a and miR-133b may predict chemosensitivity of patients with ESCC undergoing paclitaxel-based chemotherapy, implying its importance in applying ‘personalized cancer medicine’ in the clinical treatment of ESCC. We also identified combined expression of miR-133a and miR-133b as an effective prognostic marker of this malignancy.
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References
Uemura N, Kondo T. Current status of predictive biomarkers for neoadjuvant therapy in esophageal cancer. World J Gastrointest Pathophysiol. 2014;5:322–34.
D’Journo XB, Thomas PA. Current management of esophageal cancer. J Thorac Dis. 2014;6(Suppl 2):S253–64.
Nakajima M, Kato H. Treatment options for esophageal squamous cell carcinoma. Expert Opin Pharmacother. 2013;14:1345–54.
Baba Y, Watanabe M, Yoshida N, Baba H. Neoadjuvant treatment for esophageal squamous cell carcinoma. World J Gastrointest Oncol. 2014;6:121–8.
Xu Y, Yu X, Chen Q, Mao W. Neoadjuvant versus adjuvant treatment: which one is better for resectable esophageal squamous cell carcinoma? World J Surg Oncol. 2012;10:173.
Lehrbach DM, Nita ME, Cecconello I. Molecular aspects of esophageal squamous cell carcinoma carcinogenesis. Arq Gastroenterol. 2003;40:256–61.
van Rooij E, Kauppinen S. Development of microRNA therapeutics is coming of age. EMBO Mol Med. 2014;6:851–64.
Cipollini M, Landi S, Gemignani F. MicroRNA binding site polymorphisms as biomarkers in cancer management and research. Pharmgenomics Pers Med. 2014;7:173–91.
Wahid F, Khan T, Kim YY. MicroRNA and diseases: therapeutic potential as new generation of drugs. Biochimie. 2014;104C:12–26.
Chen D, Cabay RJ, Jin Y, Wang A, Lu Y, Shah-Khan M, Zhou X. MicroRNA deregulations in head and neck squamous cell carcinomas. J Oral Maxillofac Res. 2013;4:e2.
Wang Y, Wang Q, Zhang N, Ma H, Gu Y, Tang H, Xu Z, Gao Y. Identification of microRNAs as novel biomarkers for detecting esophageal squamous cell carcinoma in Asians: a meta-analysis. Tumour Biol. 2014 In press.
Chen Z, Li J, Tian L, Zhou C, Gao Y, Zhou F, Shi S, Feng X, Sun N, Yao R, Shao K, Li N, Qiu B, Tan F, He J. MiRNA expression profile reveals a prognostic signature for esophageal squamous cell carcinoma. Cancer Lett. 2014;350:34–42.
Lu J, Lu N, Xue L, Jin M. Different expression of miRNAs in early esophageal squamous cell carcinoma with differential prognosis. Dis Esophagus. 2014 In press.
Yu H, Lu Y, Li Z, Wang Q. microRNA-133: expression, function and therapeutic potential in muscle diseases and cancer. Curr Drug Targets. 2014;15:817–28.
Feng Y, Niu LL, Wei W, Zhang WY, Li XY, Cao JH, Zhao SH. A feedback circuit between miR-133 and the ERK1/2 pathway involving an exquisite mechanism for regulating myoblast proliferation and differentiation. Cell Death Dis. 2013;4:e934.
Zhou Y, Wu D, Tao J, Qu P, Zhou Z, Hou J. MicroRNA-133 inhibits cell proliferation, migration and invasion by targeting epidermal growth factor receptor and its downstream effector proteins in bladder cancer. Scand J Urol. 2013;47:423–32.
Nohata N, Hanazawa T, Enokida H, Seki N. microRNA-1/133a and microRNA-206/133b clusters: dysregulation and functional roles in human cancers. Oncotarget. 2012;3:9–21.
Wang LL, Du LT, Li J, Liu YM, Qu AL, Yang YM, Zhang X, Zheng GX, Wang CX. Decreased expression of miR-133a correlates with poor prognosis in colorectal cancer patients. World J Gastroenterol. 2014;20:11340–6.
Luo J, Zhou J, Cheng Q, Zhou C, Ding Z. Role of microRNA-133a in epithelial ovarian cancer pathogenesis and progression. Oncol Lett. 2014;7:1043–8.
Wang LK, Hsiao TH, Hong TM, Chen HY, Kao SH, Wang WL, Yu SL, Lin CW, Yang PC. MicroRNA-133a suppresses multiple oncogenic membrane receptors and cell invasion in non-small cell lung carcinoma. PLoS ONE. 2014;9:e96765.
Xiang KM, Li XR. MiR-133b acts as a tumor suppressor and negatively regulates TBPL1 in colorectal cancer cells. Asian Pac J Cancer Prev. 2014;15:3767–72.
Karatas OF, Guzel E, Suer I, Ekici ID, Caskurlu T, Creighton CJ, Ittmann M, Ozen M. miR-1 and miR-133b are differentially expressed in patients with recurrent prostate cancer. PLoS ONE. 2014;9:e98675.
Zhao H, Li M, Li L, Yang X, Lan G, Zhang Y. MiR-133b is down-regulated in human osteosarcoma and inhibits osteosarcoma cells proliferation, migration and invasion, and promotes apoptosis. PLoS ONE. 2013;8:e83571.
Cristobal I, Madoz-Gurpide J, Martin-Aparicio E, Carames C, Aguilera O, Rojo F, Garcia-Foncillas J. The tumour suppressor miR-133b is markedly downregulated in liver metastatic colorectal cancer. Br J Cancer. 2014 In press.
Qin W, Dong P, Ma C, Mitchelson K, Deng T, Zhang L, Sun Y, Feng X, Ding Y, Lu X, He J, Wen H, Cheng J. MicroRNA-133b is a key promoter of cervical carcinoma development through the activation of the ERK and AKT1 pathways. Oncogene. 2012;31:4067–75.
Zhao Y, Huang J, Zhang L, Qu Y, Li J, Yu B, Yan M, Yu Y, Liu B, Zhu Z. MiR-133b is frequently decreased in gastric cancer and its overexpression reduces the metastatic potential of gastric cancer cells. BMC Cancer. 2014;14:34.
Zhang C, Wang C, Chen X, Yang C, Li K, Wang J, Dai J, Hu Z, Zhou X, Chen L, Zhang Y, Li Y, Qiu H, Xing J, Liang Z, Ren B, Yang C, Zen K, Zhang CY. Expression profile of microRNAs in serum: a fingerprint for esophageal squamous cell carcinoma. Clin Chem. 2010;56:1871–9.
Suzuki S, Yokobori T, Tanaka N, Sakai M, Sano A, Inose T, Sohda M, Nakajima M, Miyazaki T, Kato H, Kuwano H. CD47 expression regulated by the miR-133a tumor suppressor is a novel prognostic marker in esophageal squamous cell carcinoma. Oncol Rep. 2012;28:465–72.
Kano M, Seki N, Kikkawa N, Fujimura L, Hoshino I, Akutsu Y, Chiyomaru T, Enokida H, Nakagawa M, Matsubara H. miR-145, miR-133a and miR-133b: tumor-suppressive miRNAs target FSCN1 in esophageal squamous cell carcinoma. Int J Cancer. 2010;127:2804–14.
Fu HL, de Wu P, Wang XF, Wang JG, Jiao F, Song LL, Xie H, Wen XY, Shan HS, Du YX, Zhao YP. Altered miRNA expression is associated with differentiation, invasion, and metastasis of esophageal squamous cell carcinoma (ESCC) in patients from Huaian, China. Cell Biochem Biophys. 2013;67:657–68.
Kojima S, Chiyomaru T, Kawakami K, Yoshino H, Enokida H, Nohata N, Fuse M, Ichikawa T, Naya Y, Nakagawa M, Seki N. Tumour suppressors miR-1 and miR-133a target the oncogenic function of purine nucleoside phosphorylase (PNP) in prostate cancer. Br J Cancer. 2012;106:405–13.
Moriya Y, Nohata N, Kinoshita T, Mutallip M, Okamoto T, Yoshida S, Suzuki M, Yoshino I, Seki N. Tumor suppressive microRNA-133a regulates novel molecular networks in lung squamous cell carcinoma. J Hum Genet. 2012;57:38–45.
Kinoshita T, Nohata N, Fuse M, Hanazawa T, Kikkawa N, Fujimura L, Watanabe-Takano H, Yamada Y, Yoshino H, Enokida H, Nakagawa M, Okamoto Y, Seki N. Tumor suppressive microRNA-133a regulates novel targets: moesin contributes to cancer cell proliferation and invasion in head and neck squamous cell carcinoma. Biochem Biophys Res Commun. 2012;418:378–83.
Hsu FM, Lin CC, Lee JM, Chang YL, Hsu CH, Tsai YC, Lee YC, Cheng JC. Improved local control by surgery and paclitaxel-based chemoradiation for esophageal squamous cell carcinoma: results of a retrospective non-randomized study. J Surg Oncol. 2008;98:34–41.
Chen WW, Lin CC, Huang TC, Cheng AL, Yeh KH, Hsu CH. Prognostic factors of metastatic or recurrent esophageal squamous cell carcinoma in patients receiving three-drug combination chemotherapy. Anticancer Res. 2013;33:4123–8.
Huang JX, Shen SL, Lin M, Xiao W, Chen WC, Lin MS, Yu H, Chen P, Qian RY. Cyclin A overexpression is associated with chemosensitivity to paclitaxel-based chemotherapy in patients with esophageal squamous cell carcinoma. Oncol Lett. 2012;4:607–11.
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Guiming Chen and Jin Peng have contributed equally in this study.
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Chen, G., Peng, J., Zhu, W. et al. Combined downregulation of microRNA-133a and microRNA-133b predicts chemosensitivity of patients with esophageal squamous cell carcinoma undergoing paclitaxel-based chemotherapy. Med Oncol 31, 263 (2014). https://doi.org/10.1007/s12032-014-0263-6
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DOI: https://doi.org/10.1007/s12032-014-0263-6