Global fecal microRNA profiling in the identification of biomarkers for colorectal cancer screening among Asians

Phua,Lee Cheng; Chue,Xiu Ping; Koh,Poh Koon; Cheah,Peh Yean; Chan,Eric Chun Yong; Ho,Han Kiat

doi:10.3892/or.2014.3193

Global fecal microRNA profiling in the identification of biomarkers for colorectal cancer screening among Asians

Authors:
- Lee Cheng Phua
- Xiu Ping Chue
- Poh Koon Koh
- Peh Yean Cheah
- Eric Chun Yong Chan
- Han Kiat Ho
View Affiliations

Affiliations: Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore 117543, Republic of Singapore, Department of Colorectal Surgery, Singapore General Hospital, Singapore 169856, Republic of Singapore
Published online on: May 16, 2014 https://doi.org/10.3892/or.2014.3193
Pages: 97-104

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Fecal microRNAs (miRNAs) are increasingly explored as non-invasive markers of colorectal cancer (CRC). However, its holistic profile in Asian CRC patients remains elusive. In the present study, the global human fecal miRNAs in Asian Chinese CRC patients was assayed to elucidate novel diagnostic fecal markers. Additionally, the influence of blood in stool on fecal miRNA levels was investigated for the first time. Microarray analysis was applied to profile the fecal miRNAs extracted from CRC patients and healthy subjects. Concurrently, surgically resected tumor and matched normal mucosae were analyzed. Potential fecal miRNA markers were further confirmed using real-time PCR in 17 CRC patients and 28 healthy subjects. Global miRNA profiling uncovered 17 fecal markers (p<0.05) differentially regulated in CRC. Fecal miR-223 and miR-451 represented robust markers in distinguishing CRC patients from healthy subjects, as evident from areas under the receiver operator characteristic curves of 0.939 and 0.971, respectively. Blood in stool affected fecal miR-451, miR-223 and miR-135b levels to a varying extent and substantially impacted the interpretation of the clinical data. Notably, a discrete set of aberrant miRNAs occurred within the tumor, indicating the presence of contributors beyond the exfoliation of tumor cells to the fecal miRNA profile. In summary, the utility of a global miRNA screening approach was successfully demonstrated in elucidating diagnostic markers of CRC. In particular, fecal miR-223 and miR-451 hold promise in detecting CRC.

View Figures

View References

1	Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM: GLOBOCAN 2008 v2.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10 (Internet). International Agency for Research on Cancer; Lyon: 2010, http://globocan.iarc.fr. access date: 11/06/2013
2	Moghimi-Dehkordi B and Safaee A: An overview of colorectal cancer survival rates and prognosis in Asia. World J Gastrointest Oncol. 4:71–75. 2012. View Article : Google Scholar : PubMed/NCBI
3	Sung JJ, Lau JY, Goh KL and Leung WK: Increasing incidence of colorectal cancer in Asia: implications for screening. Lancet Oncol. 6:871–876. 2005. View Article : Google Scholar : PubMed/NCBI
4	Ransohoff DF and Sandler RS: Clinical practice. Screening for colorectal cancer. N Engl J Med. 346:40–44. 2002. View Article : Google Scholar : PubMed/NCBI
5	Osborn NK and Ahlquist DA: Stool screening for colorectal cancer: molecular approaches. Gastroenterology. 128:192–206. 2005. View Article : Google Scholar : PubMed/NCBI
6	Takai T, Kanaoka S, Yoshida K, et al: Fecal cyclooxygenase 2 plus matrix metalloproteinase 7 mRNA assays as a marker for colorectal cancer screening. Cancer Epidemiol Biomarkers Prev. 18:1888–1893. 2009. View Article : Google Scholar : PubMed/NCBI
7	Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
8	Hwang HW and Mendell JT: MicroRNAs in cell proliferation, cell death, and tumorigenesis. Br J Cancer. 94:776–780. 2006. View Article : Google Scholar : PubMed/NCBI
9	Calin GA and Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer. 6:857–866. 2006. View Article : Google Scholar : PubMed/NCBI
10	Kong YW, Ferland-McCollough D, Jackson TJ and Bushell M: microRNAs in cancer management. Lancet Oncol. 13:e249–e258. 2012. View Article : Google Scholar : PubMed/NCBI
11	Esquela-Kerscher A and Slack FJ: Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 6:259–269. 2006. View Article : Google Scholar
12	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
13	Bandres E, Cubedo E, Agirre X, et al: Identification by Real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues. Mol Cancer. 5:292006. View Article : Google Scholar : PubMed/NCBI
14	Wang CJ, Zhou ZG, Wang L, et al: Clinicopathological significance of microRNA-31, -143 and -145 expression in colorectal cancer. Dis Markers. 26:27–34. 2009. View Article : Google Scholar : PubMed/NCBI
15	Chen Y, Song Y, Wang Z, et al: Altered expression of miR-148a and miR-152 in gastrointestinal cancers and its clinical significance. J Gastrointest Surg. 14:1170–1179. 2010. View Article : Google Scholar : PubMed/NCBI
16	Slaby O, Svoboda M, Fabian P, et al: Altered expression of miR-21, miR-31, miR-143 and miR-145 is related to clinicopathologic features of colorectal cancer. Oncology. 72:397–402. 2007. View Article : Google Scholar : PubMed/NCBI
17	Hamfjord J, Stangeland AM, Hughes T, et al: Differential expression of miRNAs in colorectal cancer: comparison of paired tumor tissue and adjacent normal mucosa using high-throughput sequencing. PLoS One. 7:e341502012. View Article : Google Scholar
18	Faltejskova P, Svoboda M, Srutova K, et al: Identification and functional screening of microRNAs highly deregulated in colorectal cancer. J Cell Mol Med. 16:2655–2666. 2012. View Article : Google Scholar : PubMed/NCBI
19	Xu XM, Qian JC, Deng ZL, et al: Expression of miR-21, miR-31, miR-96 and miR-135b is correlated with the clinical parameters of colorectal cancer. Oncol Lett. 4:339–345. 2012.PubMed/NCBI
20	Mazeh H, Mizrahi I, Ilyayev N, et al: The diagnostic and prognostic role of microRNA in colorectal cancer - a comprehensive review. J Cancer. 4:281–295. 2013. View Article : Google Scholar : PubMed/NCBI
21	Ahmed FE, Jeffries CD, Vos PW, et al: Diagnostic microRNA markers for screening sporadic human colon cancer and active ulcerative colitis in stool and tissue. Cancer Genomics Proteomics. 6:281–295. 2009.
22	Koga Y, Yasunaga M, Takahashi A, et al: MicroRNA expression profiling of exfoliated colonocytes isolated from feces for colorectal cancer screening. Cancer Prev Res (Phila). 3:1435–1442. 2010. View Article : Google Scholar : PubMed/NCBI
23	Link A, Balaguer F, Shen Y, et al: Fecal microRNAs as novel biomarkers for colon cancer screening. Cancer Epidemiol Biomarkers Prev. 19:1766–1774. 2010. View Article : Google Scholar : PubMed/NCBI
24	Wu CW, Ng SS, Dong YJ, et al: Detection of miR-92a and miR-21 in stool samples as potential screening biomarkers for colorectal cancer and polyps. Gut. 61:739–745. 2011.PubMed/NCBI
25	Yamazaki N, Koga Y, Yamamoto S, et al: Application of the fecal microRNA test to the residuum from the fecal occult blood test. Jpn J Clin Oncol. 43:726–733. 2013. View Article : Google Scholar : PubMed/NCBI
26	Li JM, Zhao RH, Li ST, et al: Down-regulation of fecal miR-143 and miR-145 as potential markers for colorectal cancer. Saudi Med J. 33:24–29. 2012.PubMed/NCBI
27	Kalimutho M, Del Vecchio Blanco G, Di Cecilia S, et al: Differential expression of miR-144* as a novel fecal-based diagnostic marker for colorectal cancer. J Gastroenterol. 46:1391–1402. 2011.
28	Ahmed FE, Ahmed NC, Vos PW, et al: Diagnostic microRNA markers to screen for sporadic human colon cancer in stool: I. Proof of principle. Cancer Genomics Proteomics. 10:93–113. 2013.PubMed/NCBI
29	Mao X, Yu Y, Boyd LK, et al: Distinct genomic alterations in prostate cancers in Chinese and Western populations suggest alternative pathways of prostate carcinogenesis. Cancer Res. 70:5207–5212. 2010. View Article : Google Scholar
30	Pritchard CC, Kroh E, Wood B, et al: Blood cell origin of circulating microRNAs: a cautionary note for cancer biomarker studies. Cancer Prev Res (Phila). 5:492–497. 2012. View Article : Google Scholar : PubMed/NCBI
31	Kirschner MB, Kao SC, Edelman JJ, et al: Haemolysis during sample preparation alters microRNA content of plasma. PLoS One. 6:e241452011. View Article : Google Scholar : PubMed/NCBI
32	Vandesompele J, De Preter K, Pattyn F, et al: Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 3:RESEARCH00342002. View Article : Google Scholar : PubMed/NCBI
33	Slaby O, Svoboda M, Michalek J and Vyzula R: MicroRNAs in colorectal cancer: translation of molecular biology into clinical application. Mol Cancer. 8:1022009. View Article : Google Scholar : PubMed/NCBI
34	Sun J, Chen Z, Tan X, et al: MicroRNA-99a/100 promotes apoptosis by targeting mTOR in human esophageal squamous cell carcinoma. Med Oncol. 30:4112013. View Article : Google Scholar : PubMed/NCBI
35	Torres A, Torres K, Pesci A, et al: Deregulation of miR-100, miR-99a and miR-199b in tissues and plasma coexists with increased expression of mTOR kinase in endometrioid endometrial carcinoma. BMC Cancer. 12:3692012. View Article : Google Scholar : PubMed/NCBI
36	Chen Z, Jin Y, Yu D, et al: Down-regulation of the microRNA-99 family members in head and neck squamous cell carcinoma. Oral Oncol. 48:686–691. 2012. View Article : Google Scholar : PubMed/NCBI
37	Huang ZM, Yang J, Shen XY, et al: MicroRNA expression profile in non-cancerous colonic tissue associated with lymph node metastasis of colon cancer. J Dig Dis. 10:188–194. 2009. View Article : Google Scholar : PubMed/NCBI
38	Li X, Zhang Y, Zhang H, et al: miRNA-223 promotes gastric cancer invasion and metastasis by targeting tumor suppressor EPB41L3. Mol Cancer Res. 824–833. 2011. View Article : Google Scholar : PubMed/NCBI
39	Li S, Li Z, Guo F, et al: miR-223 regulates migration and invasion by targeting Artemin in human esophageal carcinoma. J Biomed Sci. 18:242011. View Article : Google Scholar : PubMed/NCBI
40	Wu L, Li H, Jia CY, et al: MicroRNA-223 regulates FOXO1 expression and cell proliferation. FEBS Lett. 586:1038–1043. 2012. View Article : Google Scholar : PubMed/NCBI
41	Godlewski J, Bronisz A, Nowicki MO, Chiocca EA and Lawler S: microRNA-451: a conditional switch controlling glioma cell proliferation and migration. Cell Cycle. 9:2742–2748. 2010. View Article : Google Scholar : PubMed/NCBI
42	Godlewski J, Nowicki MO, Bronisz A, et al: MicroRNA-451 regulates LKB1/AMPK signaling and allows adaptation to metabolic stress in glioma cells. Mol Cell. 37:620–632. 2010. View Article : Google Scholar : PubMed/NCBI
43	Wang T, Zang WQ, Li M, Wang N, Zheng YL and Zhao GQ: Effect of miR-451 on the biological behavior of the esophageal carcinoma cell line EC9706. Digest Dis Sci. 58:706–714. 2013. View Article : Google Scholar : PubMed/NCBI
44	Molinari F, Felicioni L, Buscarino M, et al: Increased detection sensitivity for KRAS mutations enhances the prediction of anti-EGFR monoclonal antibody resistance in metastatic colorectal cancer. Clin Cancer Res. 17:4901–4914. 2011.PubMed/NCBI
45	Bandres E, Bitarte N, Arias F, et al: microRNA-451 regulates macrophage migration inhibitory factor production and proliferation of gastrointestinal cancer cells. Clin Cancer Res. 15:2281–2290. 2009. View Article : Google Scholar : PubMed/NCBI