Clinical significance of microRNA-21 as a biomarker in each Dukes' stage of colorectal cancer

Fukushima,Yoshihisa; Iinuma,Hisae; Tsukamoto,Mitsuo; Matsuda,Keiji; Hashiguchi,Yojiro

doi:10.3892/or.2014.3614

Clinical significance of microRNA-21 as a biomarker in each Dukes' stage of colorectal cancer

Authors:
- Yoshihisa Fukushima
- Hisae Iinuma
- Mitsuo Tsukamoto
- Keiji Matsuda
- Yojiro Hashiguchi
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Affiliations: Department of Surgery, Teikyo University School of Medicine, Itabashi-ku, Tokyo 173-0003, Japan
Published online on: November 21, 2014 https://doi.org/10.3892/or.2014.3614
Pages: 573-582

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Abstract

The potential value of microRNAs (miRNAs) as prognostic biomarkers are of interest. It is known that microRNA-21 (miR-21) is implicated in the promotion, proliferation and progression of several types of human cancers. However, the prognostic significance of miR-21 in each tumor stage of colorectal cancer (CRC) remains elusive. The objective of this study was to clarify the prognostic value of miR-21 for CRC patients at each tumor stage. The expression levels of miR-21 in the tumor tissues and normal adjacent tumor tissues of 306 CRC patients were determined by TaqMan microRNA assays. In order to clarify the miRNA profile in CRC tissues, miRNA arrays were examined. In this analysis, miR-21, miR-224, miR-96, miR-31 and miR-155 showed marked upregulation, and miR-21 showed the highest level. Upon comparison of clinicopathological factors, miR-21 expression showed significant association with depth of invasion, lymphatic and venous invasion, liver metastasis and Dukes' stage. In the Kaplan-Meier survival curve analysis of all patients, overall survival (OS) and disease-free survival (DFS) rates of the patients with high miR-21 expression were significantly worse than these rates in patients with low miR-21 expression. In the Kaplan-Meier analysis of each tumor stage, the DFS of patients with high miR-21 expression was significantly worse than patients with low miR-21 levels in Dukes' stage A tumors. In Dukes' stage B and C, patients with high miR-21 expression showed a significantly worse OS and DFS than patients with low miR-21 expression. In Dukes' stage D, patients with high miR-21 expression showed a significantly worse OS than patients with low miR-21 expression. In the Cox multivariate analysis, it was shown that miR-21 expressions in CRC tissues is an independent prognostic factor in Dukes' stage B, C and D. In conclusion, miR-21 expression may be a valuable biomarker for prediction of poor prognosis in CRC patients with Dukes' stage B, C and D.

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1	Gill S, Thomas RR and Goldberg RM: Review article: colorectal cancer chemotherapy. Aliment Pharmacol Ther. 18:683–692. 2003. View Article : Google Scholar : PubMed/NCBI
2	Aggarwal S and Chu E: Current therapies for advanced colorectal cancer. Oncology. 19:589–595. 2005.PubMed/NCBI
3	André T, Boni C, Mounedji-Boudiat L, et al: Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 350:2343–2351. 2004. View Article : Google Scholar : PubMed/NCBI
4	Meropol NJ and Schulman KA: Cost of cancer care: issues and implications. J Clin Oncol. 25:180–186. 2007. View Article : Google Scholar : PubMed/NCBI
5	Chung KY and Kelsen D: Adjuvant therapy for stage II colorectal cancer; who and with what? Curr Treat Options Gastroenterol. 9:272–280. 2006. View Article : Google Scholar : PubMed/NCBI
6	Aslam MI, Taylor K, Pringle JH and Jameson JS: microRNAs are novel biomarkers of colorectal cancer. Br J Surg. 96:702–710. 2009. View Article : Google Scholar : PubMed/NCBI
7	Chen CZ, Li L, Lodish HF and Bartel DP: MicroRNAs modulate hematopoietic lineage differentiation. Science. 303:83–86. 2004. View Article : Google Scholar
8	Croce CM and Calin GA: miRNAs, cancer, and stem cell division. Cell. 122:6–7. 2005. View Article : Google Scholar : PubMed/NCBI
9	Caldas C and Brenton JD: Sizing up miRNAs as cancer genes. Nat Med. 11:712–714. 2005. View Article : Google Scholar : PubMed/NCBI
10	Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, Aldler H, Rattan S, Keating M, Rai K, Rassenti L, Kipps T, Negrini M, Bullrich F and Croce CM: Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA. 99:15524–15529. 2002. View Article : Google Scholar
11	Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A, Labourier E, Reinert KL, Brown D and Slack FJ: RAS is regulated by the let-7 microRNA family. Cell. 120:635–647. 2005. View Article : Google Scholar : PubMed/NCBI
12	Calin GA, Ferracin M, Cimmino A, Di Leva G, Shimizu M, Wojcik SE, Iorio MV, Visone R, Sever NI, Fabbri M, Iuliano R, Palumbo T, Pichiorri F, Roldo C, Garzon R, Sevignani C, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M and Croce CM: A microRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med. 353:1793–1801. 2005. View Article : Google Scholar : PubMed/NCBI
13	He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, Powers S, Cordon-Cardo C, Lowe SW, Hannon GJ and Hammond SM: A microRNA polycistron as a potential human oncogene. Nature. 435:828–833. 2005. View Article : Google Scholar : PubMed/NCBI
14	Yan LX, Huang XF, Shao Q, Huang MY, Deng L, Wu QL, Zeng YX and Shao JY: MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis. RNA. 14:2348–2360. 2008. View Article : Google Scholar : PubMed/NCBI
15	Asangani IA, Rasheed SA, Nikolova DA, Leupold JH, Colburn NH, Post S and Allgayer H: MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene. 27:2128–2136. 2008. View Article : Google Scholar
16	Schetter AJ, Leung SY, Sohn JJ, Zanetti KA, Bowman ED, Yanaihara N, Yuen ST, Chan TL, Kwong DL, Au GK, Liu CG, Calin GA, Croce CM and Harris CC: MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA. 299:425–436. 2008. View Article : Google Scholar : PubMed/NCBI
17	Slaby O, Svoboda M, Fabian P, Smerdova T, Knoflickova D, Bednarikova M, Nenutil R and Vyzula R: Altered expression of miR21, miR-31, miR-143 and miR-145 is related to clinicopathological features of colorectal cancer. Oncology. 72:397–402. 2007. View Article : Google Scholar
18	Chan JA, Krichevsky AM and Kosik KS: MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res. 65:6029–6033. 2005. View Article : Google Scholar : PubMed/NCBI
19	Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, Magri E, Pedriali M, Fabbri M, Campiglio M, Ménard S, Palazzo JP, Rosenberg A, Musiani P, Volinia S, Nenci I, Calin GA, Querzoli P, Negrini M and Croce CM: MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 65:7065–7070. 2005. View Article : Google Scholar : PubMed/NCBI
20	Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST and Patel T: MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology. 133:647–658. 2007. View Article : Google Scholar : PubMed/NCBI
21	Esquela-Kerscher A and Slack FJ: Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 6:259–269. 2006. View Article : Google Scholar : PubMed/NCBI
22	Kloosterman WP and Plasterk RH: The diverse functions of microRNAs in animal development and disease. Dev Cell. 11:441–450. 2006. View Article : Google Scholar : PubMed/NCBI
23	Chang KH, Miler N, Kheirelseid EA, et al: MicroRNA-21 and PDCD4 expression in colorectal cancer. Eur J Surg Oncol. 37:597–603. 2011. View Article : Google Scholar : PubMed/NCBI
24	Wang ZX, Lu BB, Wang H, et al: MicroRNA-21 modulates chemosensitivity of breast cancer cells to doxorubicin by targeting PTEN. Arch Med Res. 42:281–290. 2011. View Article : Google Scholar : PubMed/NCBI
25	Zhu S, Si ML, Wu H and Mo YY: MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1). J Biol Chem. 282:14328–14336. 2007. View Article : Google Scholar : PubMed/NCBI
26	Ziyan W, Shuhua Y, Xiufang W and Xianoyun L: MicroRNA-21 is involved in osteosarcoma cell invasion and migration. Med Oncol. 28:1469–1474. 2011. View Article : Google Scholar
27	Liu M, Tang Q, Qiu M, et al: miR-21 targets the tumor suppressor RhoB and regulates proliferation, invasion and apoptosis in colorectal cancer cells. FEBS Lett. 585:2998–3005. 2011. View Article : Google Scholar : PubMed/NCBI
28	Torres A, Torres K, Paszkowski T, et al: Highly increased maspin expression corresponds with up-regulation of miR-21 in colorectal cancer: a preliminary report. Int J Gynecol Cancer. 21:8–14. 2011. View Article : Google Scholar : PubMed/NCBI
29	Horiuchi A, Iinuma H, Akahane T, Shimada R and Watanabe T: Prognostic significance of PDCD4 expression and association with microRNA-21 in each Dukes’ stage of colorectal cancer patients. Oncol Rep. 27:1384–1392. 2012.PubMed/NCBI