Plasma miR‑200c and miR‑18a as potential biomarkers for the detection of colorectal carcinoma

Zhang,Guang-Jun; Zhou,Tong; Liu,Zuo-Liang; Tian,Hong-Peng; Xia,Shu-Sen

doi:10.3892/mco.2013.61

Plasma miR‑200c and miR‑18a as potential biomarkers for the detection of colorectal carcinoma

Authors:
- Guang-Jun Zhang
- Tong Zhou
- Zuo-Liang Liu
- Hong-Peng Tian
- Shu-Sen Xia
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Affiliations: The First Department of General Surgery, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
Published online on: January 7, 2013 https://doi.org/10.3892/mco.2013.61
Pages: 379-384

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Abstract

It has been demonstrated that there are abundant stable microRNAs (miRNAs) in plasma/serum, which can be detected and are potentially disease‑specific. The aim of this study was to investigate whether plasma miR‑200c and miR‑18a can be used as biomarkers for the detection of colorectal carcinoma (CRC). This study was divided into three parts: i) confirmation of higher miR‑200c and miR‑18a levels in primary CRC tissues compared to normal colorectal tissues; ii) evaluation of plasma miR‑200c and miR‑18a expression by comparing 78 patients with 86 healthy volunteers and iii) comparison of miR‑200c and miR‑18a levels in paired pre-and post-operative plasma in cancer patients who underwent curative CRC resection. Results showed that the expression of miR‑200c and miR‑18a was significantly higher in CRC compared to normal tissues. The plasma levels of miR‑200c and miR‑18a were significantly higher in CRC patients compared to controls. miR‑200c yielded an area under the receiver‑operating characteristics (ROC) curve (AUC) of 0.749 and miR‑18a yielded an AUC of 0.804 when distinguishing CRC patients from the controls. Combined ROC analyses using the two miRNAs revealed an elevated AUC of 0.839 with 84.6% sensitivity and 75.6% specificity in discriminating CRC. Plasma levels of miR‑200c and miR‑18a were significantly lower in post‑operative compared to pre‑operative samples. The results of this study suggest that plasma miR‑200c and miR‑18a are significantly elevated in the plasma of CRC patients and that they may serve as non-invasive molecular markers for CRC screening.

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1	Parkin DM, Bray F, Ferlay J and Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 55:74–108. 2005. View Article : Google Scholar
2	Levin B, Lieberman DA, McFarland B, et al: Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. CA Cancer J Clin. 58:130–160. 2008. View Article : Google Scholar
3	Mandel JS: Screening for colorectal cancer. Gastroenterol Clin North Am. 37:97–115. 2008. View Article : Google Scholar
4	Mitchell PS, Parkin RK, Kroh EM, et al: Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA. 105:10513–10518. 2008. View Article : Google Scholar : PubMed/NCBI
5	Chen X, Ba Y, Ma L, et al: Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 18:997–1006. 2008. View Article : Google Scholar : PubMed/NCBI
6	Wang J, Chen J, Chang P, et al: MicroRNAs in plasma of pancreatic ductal adenocarcinoma patients as novel blood-based biomarkers of disease. Cancer Prev Res (Phila). 2:807–813. 2009. View Article : Google Scholar : PubMed/NCBI
7	Ng EK, Chong WW, Jin H, et al: Differential expression of microRNAs in plasma of patients with colorectal cancer: a potential marker for colorectal cancer screening. Gut. 58:1375–1381. 2009. View Article : Google Scholar : PubMed/NCBI
8	Heneghan HM, Miller N, Lowery AJ, et al: Circulating microRNAs as novel minimally invasive biomarkers for breast cancer. Ann Surg. 251:499–505. 2010. View Article : Google Scholar : PubMed/NCBI
9	Tsujiura M, Ichikawa D, Komatsu S, et al: Circulating microRNAs in plasma of patients with gastric cancers. Br J Cancer. 102:1174–1179. 2010. View Article : Google Scholar : PubMed/NCBI
10	Xi Y, Formentini A, Chien M, et al: Prognostic values of microRNAs in colorectal cancer. Biomark Insights. 2:113–121. 2006.PubMed/NCBI
11	Motoyama K, Inoue H, Takatsuno Y, et al: Over- and under-expressed microRNAs in human colorectal cancer. Int J Oncol. 34:1069–1075. 2009.PubMed/NCBI
12	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. 105:1733–1740. 2011. View Article : Google Scholar : PubMed/NCBI
13	He L, Thomson JM, Hemann MT, et al: A microRNA polycistron as a potential human oncogene. Nature. 435:828–833. 2005. View Article : Google Scholar : PubMed/NCBI
14	Voorhoeve PM, le Sage C, Schrier M, et al: A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors. Cell. 124:1169–1181. 2006. View Article : Google Scholar
15	Johnson SM, Grosshans H, Shingara J, et al: RAS is regulated by the let-7 microRNA family. Cell. 120:635–647. 2005. View Article : Google Scholar : PubMed/NCBI
16	Mattie MD, Benz CC, Bowers J, et al: Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies. Mol Cancer. 5:242006. View Article : Google Scholar
17	Yanaihara N, Caplen N, Bowman E, et al: Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 9:189–198. 2006. View Article : Google Scholar : PubMed/NCBI
18	Huang Z, Huang D, Ni S, et al: Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer. Int J Cancer. 127:118–126. 2010. View Article : Google Scholar : PubMed/NCBI
19	Diosdado B, van de Wiel MA, Terhaar Sive, Droste JS, et al: MiR-17-92 cluster is associated with 13q gain and c-myc expression during colorectal adenoma to adenocarcinoma progression. Br J Cancer. 101:707–714. 2009. View Article : Google Scholar : PubMed/NCBI
20	Connolly E, Melegari M, Landgraf P, et al: Elevated expression of the miR-17-92 polycistron and miR-21 in hepadnavirus-associated hepatocellular carcinoma contributes to the malignant phenotype. Am J Pathol. 173:856–864. 2008. View Article : Google Scholar
21	Yao Y, Suo AL, Li ZF, et al: MicroRNA profiling of human gastric cancer. Mol Med Rep. 2:963–970. 2009.PubMed/NCBI
22	Park SM, Gaur AB, Lengyel E, et al: The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Develop. 22:894–907. 2008. View Article : Google Scholar : PubMed/NCBI
23	Korpal M, Lee ES, Hu G, et al: The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. J Biol Chem. 283:14910–14914. 2008. View Article : Google Scholar : PubMed/NCBI
24	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. 29:618–626. 2012. View Article : Google Scholar : PubMed/NCBI