Serum microRNA-193b as a promising biomarker for prediction of chemoradiation sensitivity in esophageal squamous cell carcinoma patients

Chan,Chung Man; Lai,Kenneth K. Y.; Ng,Enders K. O.; Kiang,Mei Na; Kwok,Tiffany W. H.; Wang,Hector K.; Chan,Kwok Wah; Law,Tsz Ting; Tong,Daniel K.; Chan,Kin Tak; Lee,Nikki P.; Law,Simon

doi:10.3892/ol.2017.7698

Serum microRNA-193b as a promising biomarker for prediction of chemoradiation sensitivity in esophageal squamous cell carcinoma patients

Authors:
- Chung Man Chan
- Kenneth K. Y. Lai
- Enders K. O. Ng
- Mei Na Kiang
- Tiffany W. H. Kwok
- Hector K. Wang
- Kwok Wah Chan
- Tsz Ting Law
- Daniel K. Tong
- Kin Tak Chan
- Nikki P. Lee
- Simon Law
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Affiliations: Department of Surgery, The University of Hong Kong, Hong Kong, SAR, P.R. China, Department of Pathology, The University of Hong Kong, Hong Kong, SAR, P.R. China
Published online on: December 27, 2017 https://doi.org/10.3892/ol.2017.7698
Pages: 3273-3280

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Abstract

Esophageal squamous cell carcinoma (ESCC) is the most predominantly occurring type of esophageal cancer worldwide. Locally advanced ESCC patients are treated by neoadjuvant chemoradiation for tumor downstaging prior to tumor resection. Patients receiving this treatment have an increased expectation of cure via the following tumor resection and have better survival outcomes. However, not all patients respond well to chemoradiation and poor responders suffer from treatment‑associated toxicity and complications without benefits. No method is currently available to predict patient chemoradiation response and to exclude poor responders from ineffective treatment. To address this clinical limitation, the present study aimed to identify non‑invasive biomarkers for predicting patient chemoradiation response. Due to the features of microRNA (miRNA) in cancer diagnosis, prognosis and treatment response prediction, serum miRNA arrays were performed to identify potential miRNA(s) that may be used for chemoradiation response prediction in ESCC. Using an miRNA array to compare pre‑treatment serum sample pools from 10 good responders and 10 poor responders, the present study identified miR‑193b, miR‑942 and miR‑629* as candidate miRNAs for predicting chemoradiation response. Subsequent validation using reverse transcription‑quantitative polymerase chain reaction confirmed that miR‑193b, however not miR‑942 and miR‑629*, were significantly increased in sera from 24 good responders, compared with 23 poor responders. Further analyses using the receiver operating characteristic curve revealed a strong predictive power of serum miR‑193b on discriminating good responders from poor responders to chemoradiation. In addition, a high serum level of miR‑193b was significantly associated with better survival outcomes. Therefore, serum miR‑193b may be considered a promising biomarker for predicting chemoradiation response and post-therapy survival of ESCC patients.

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1	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
2	Enzinger PC and Mayer RJ: Esophageal cancer. N Engl J Med. 349:2241–2252. 2003. View Article : Google Scholar : PubMed/NCBI
3	Hiyama T, Yoshihara M, Tanaka S and Chayama K: Genetic polymorphisms and esophageal cancer risk. Int J Cancer. 121:1643–1658. 2007. View Article : Google Scholar : PubMed/NCBI
4	Tong DK, Law S, Kwong DL, Wei WI, Ng RW and Wong KH: Current management of cervical esophageal cancer. World J Surg. 35:600–607. 2011. View Article : Google Scholar : PubMed/NCBI
5	Law S, Kwong DL, Kwok KF, Wong KH, Chu KM, Sham JS and Wong J: Improvement in treatment results and long-term survival of patients with esophageal cancer: Impact of chemoradiation and change in treatment strategy. Ann Surg. 238:339–348. 2003.PubMed/NCBI
6	Allum WH, Blazeby JM, Griffin SM, Cunningham D, Jankowski JA and Wong R; Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland, the British Society of Gastroenterology and the British Association of Surgical Oncology, : Guidelines for the management of oesophageal and gastric cancer. Gut. 60:1449–1472. 2011. View Article : Google Scholar : PubMed/NCBI
7	Di Leva G, Garofalo M and Croce CM: MicroRNAs in cancer. Annu Rev Pathol. 9:287–314. 2014. View Article : Google Scholar : PubMed/NCBI
8	Mostert B, Sieuwerts AM, Martens JW and Sleijfer S: Diagnostic applications of cell-free and circulating tumor cell-associated miRNAs in cancer patients. Expert Rev Mol Diagn. 11:259–275. 2011.PubMed/NCBI
9	Garofalo M, Leva GD and Croce CM: MicroRNAs as anti-cancer therapy. Curr Pharm Des. 20:5328–5335. 2014. View Article : Google Scholar : PubMed/NCBI
10	Tumilson CA, Lea RW, Alder JE and Shaw L: Circulating microRNA biomarkers for glioma and predicting response to therapy. Mol Neurobiol. 50:545–558. 2014. View Article : Google Scholar : PubMed/NCBI
11	Schwarzenbach H: The potential of circulating nucleic acids as components of companion diagnostics for predicting and monitoring chemotherapy response. Expert Rev Mol Diagn. 15:267–275. 2015. View Article : Google Scholar : PubMed/NCBI
12	Chen X, Xu Y, Liao X, Liao R, Zhang L, Niu K, Li T, Li D, Chen Z, Duan Y and Sun J: Plasma miRNAs in predicting radiosensitivity in non-small cell lung cancer. Tumour Biol. 37:11927–11936. 2016. View Article : Google Scholar : PubMed/NCBI
13	DAngelo E, Fassan M, Maretto I, Pucciarelli S, Zanon C, Digito M, Rugge M, Nitti D and Agostini M: Serum miR-125b is a non-invasive predictive biomarker of the pre-operative chemoradiotherapy responsiveness in patients with rectal adenocarcinoma. Oncotarget. 7:28647–28657. 2016.PubMed/NCBI
14	Wen J, Luo K, Liu H, Liu S, Lin G, Hu Y, Zhang X, Wang G, Chen Y, Chen Z, et al: MiRNA expression analysis of pretreatment biopsies predicts the pathological response of esophageal squamous cell carcinomas to neoadjuvant chemoradiotherapy. Ann Surg. 263:942–948. 2016. View Article : Google Scholar : PubMed/NCBI
15	Hoy AM and Buck AH: Extracellular small RNAs: What, where, why? Biochem Soc Trans. 40:886–890. 2012. View Article : Google Scholar : PubMed/NCBI
16	Jarry J, Schadendorf D, Greenwood C, Spatz A and van Kempen LC: The validity of circulating microRNAs in oncology: Five years of challenges and contradictions. Mol Oncol. 8:819–829. 2014. View Article : Google Scholar : PubMed/NCBI
17	Cortez MA, Bueso-Ramos C, Ferdin J, Lopez-Berestein G, Sood AK and Calin GA: MicroRNAs in body fluids-the mix of hormones and biomarkers. Nat Rev Clin Oncol. 8:467–477. 2011. View Article : Google Scholar : PubMed/NCBI
18	Tong DK, Law S, Kwong DL, Chan KW, Lam AK and Wong KH: Histological regression of squamous esophageal carcinoma assessed by percentage of residual viable cells after neoadjuvant chemoradiation is an important prognostic factor. Ann Surg Oncol. 17:2184–2192. 2010. View Article : Google Scholar : PubMed/NCBI
19	Liu AM, Yao TJ, Wang W, Wong KF, Lee NP, Fan ST, Poon RT, Gao C and Luk JM: Circulating miR-15b and miR-130b in serum as potential markers for detecting hepatocellular carcinoma: A retrospective cohort study. BMJ Open. 2:e0008252012. View Article : Google Scholar : PubMed/NCBI
20	Liu AM, Xu Z, Shek FH, Wong KF, Lee NP, Poon RT, Chen J and Luk JM: miR-122 targets pyruvate kinase M2 and affects metabolism of hepatocellular carcinoma. PLoS One. 9:e868722014. View Article : Google Scholar : PubMed/NCBI
21	Tsang FH, Au V, Lu WJ, Shek FH, Liu AM, Luk JM, Fan ST, Poon RT and Lee NP: Prognostic marker microRNA-125b inhibits tumorigenic properties of hepatocellular carcinoma cells via suppressing tumorigenic molecule eIF5A2. Dig Dis Sci. 59:2477–2487. 2014. View Article : Google Scholar : PubMed/NCBI
22	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
23	Sun S, Poon RT, Lee NP, Yeung C, Chan KL, Ng IO, Day PJ and Luk JM: Proteomics of hepatocellular carcinoma: Serum vimentin as a surrogate marker for small tumors (<or=2 cm). J Proteome Res. 9:1923–1930. 2010. View Article : Google Scholar : PubMed/NCBI
24	Berger AC, Farma J, Scott WJ, Freedman G, Weiner L, Cheng JD, Wang H and Goldberg M: Complete response to neoadjuvant chemoradiotherapy in esophageal carcinoma is associated with significantly improved survival. J Clin Oncol. 23:4330–4337. 2005. View Article : Google Scholar : PubMed/NCBI
25	Stahl M, Stuschke M, Lehmann N, Meyer HJ, Walz MK, Seeber S, Klump B, Budach W, Teichmann R, Schmitt M, et al: Chemoradiation with and without surgery in patients with locally advanced squamous cell carcinoma of the esophagus. J Clin Oncol. 23:2310–2317. 2005. View Article : Google Scholar : PubMed/NCBI
26	Bonnetain F, Bouché O, Michel P, Mariette C, Conroy T, Pezet D, Roullet B, Seitz JF, Paillot B, Arveux P, et al: A comparative longitudinal quality of life study using the Spitzer quality of life index in a randomized multicenter phase III trial (FFCD 9102): Chemoradiation followed by surgery compared with chemoradiation alone in locally advanced squamous resectable thoracic esophageal cancer. Ann Oncol. 17:827–834. 2006. View Article : Google Scholar : PubMed/NCBI
27	Tanaka K, Mohri Y, Ohi M, Yokoe T, Koike Y, Morimoto Y, Miki C, Tonouchi H and Kusunoki M: Excision-repair cross-complementing 1 predicts response to cisplatin-based neoadjuvant chemoradiotherapy in patients with esophageal squamous cell carcinoma. Mol Med Rep. 2:903–909. 2009. View Article : Google Scholar : PubMed/NCBI
28	Duong C, Greenawalt DM, Kowalczyk A, Ciavarella ML, Raskutti G, Murray WK, Phillips WA and Thomas RJ: Pretreatment gene expression profiles can be used to predict response to neoadjuvant chemoradiotherapy in esophageal cancer. Ann Surg Oncol. 14:3602–3609. 2007. View Article : Google Scholar : PubMed/NCBI
29	Wen J, Yang H, Liu MZ, Luo KJ, Liu H, Hu Y, Zhang X, Lai RC, Lin T, Wang HY and Fu JH: Gene expression analysis of pretreatment biopsies predicts the pathological response of esophageal squamous cell carcinomas to neo-chemoradiotherapy. Ann Oncol. 25:1769–1774. 2014. View Article : Google Scholar : PubMed/NCBI
30	Hemmatzadeh M, Mohammadi H, Jadidi-Niaragh F, Asghari F and Yousefi M: The role of oncomirs in the pathogenesis and treatment of breast cancer. Biomed Pharmacother. 78:129–139. 2016. View Article : Google Scholar : PubMed/NCBI
31	Kurashige J, Kamohara H, Watanabe M, Tanaka Y, Kinoshita K, Saito S, Hiyoshi Y, Iwatsuki M, Baba Y and Baba H: Serum microRNA-21 is a novel biomarker in patients with esophageal squamous cell carcinoma. J Surg Oncol. 106:188–192. 2012. View Article : Google Scholar : PubMed/NCBI
32	Tanaka K, Miyata H, Yamasaki M, Sugimura K, Takahashi T, Kurokawa Y, Nakajima K, Takiguchi S, Mori M and Doki Y: 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:S607–S615. 2013. View Article : Google Scholar : PubMed/NCBI
33	Maher SG, McDowell DT, Collins BC, Muldoon C, Gallagher WM and Reynolds JV: Serum proteomic profiling reveals that pretreatment complement protein levels are predictive of esophageal cancer patient response to neoadjuvant chemoradiation. Ann Surg. 254:809–817. 2011. View Article : Google Scholar : PubMed/NCBI
34	Hsu FM, Cheng JC, Chang YL, Lee JM, Koong AC and Chuang EY: Circulating mRNA profiling in esophageal squamous cell carcinoma identifies FAM84B as a biomarker in predicting pathological response to neoadjuvant chemoradiation. Sci Rep. 5:102912015. View Article : Google Scholar : PubMed/NCBI
35	Nyhan MJ, ODonovan TR, Boersma AW, Wiemer EA and McKenna SL: MiR-193b promotes autophagy and non-apoptotic cell death in oesophageal cancer cells. BMC Cancer. 16:1012016. View Article : Google Scholar : PubMed/NCBI
36	Chen J, Zhang X, Lentz C, Abi-Daoud M, Paré GC, Yang X, Feilotter HE and Tron VA: miR-193b regulates Mcl-1 in melanoma. Am J Pathol. 179:2162–2168. 2011. View Article : Google Scholar : PubMed/NCBI
37	Mao K, Zhang J, He C, Xu K, Liu J, Sun J, Wu G, Tan C, Zeng Y, Wang J and Xiao Z: Restoration of miR-193b sensitizes Hepatitis B virus-associated hepatocellular carcinoma to sorafenib. Cancer Lett. 352:245–252. 2014. View Article : Google Scholar : PubMed/NCBI