MicroRNAs (miRNAs) are small molecules of single strand non-coding RNAs, which are able to regulate gene expression. miRNAs have been involved in multiple cellular processes, such as proliferation, apoptosis and differentiation, thus alterations in miRNA expression have been shown to be directly linked with the pathological origin of multiple diseases, including cancer. In this way, during last few years, an increasing number of exciting advances have contributed to the understanding of miRNA roles in cancer. Moreover, researchers have exploited the special characteristics of miRNAs, such as the tissue and disease specificity or miRNA presence in blood, to explore their use as non-invasive tumour markers. In the present review, we summarize the current data on the potential usefulness of circulating miRNAs as diagnostic and prognostic tools in gastrointestinal tumours.
References
[1]
Jemal, A.; Bray, F.; Center, M.M.; Ferlay, J.; Ward, E.; Forman, D. Global cancer statistics. CA-A Cancer. J. Clin. 2011, 61, 69–90, doi:10.3322/caac.20107.
[2]
Hundt, S.; Haug, U.; Brenner, H. Blood markers for early detection of colorectal cancer: A systematic review. Cancer Epidem. Biomarker Prev. 2007, 16, 1935–1953, doi:10.1158/1055-9965.EPI-06-0994.
Lewis, B.P.; Burge, C.B.; Bartel, D.P. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 2005, 120, 15–20, doi:10.1016/j.cell.2004.12.035. 15652477
[6]
Marson, A.; Levine, S.S.; Cole, M.F.; Frampton, G.M.; Brambrink, T.; Johnstone, S.; Guenther, M.G.; Johnston, W.K.; Wernig, M.; Newman, J.; et al. Connecting microRNA genes to the core transcriptional regulatory circuitry of embryonic stem cells. Cell 2008, 134, 521–533, doi:10.1016/j.cell.2008.07.020. 18692474
[7]
Liang, Y.; Ridzon, D.; Wong, L.; Chen, C. Characterization of microRNA expression profiles in normal human tissues. BMC Genomics 2007, 8, 166, doi:10.1186/1471-2164-8-166. 17565689
Ajit, S.K. Circulating microRNAs as biomarkers, therapeutic targets, and signaling molecules. Sensors 2012, 12, 3359–3369, doi:10.3390/s120303359. 22737013
[11]
Lawrie, C.H.; Gal, S.; Dunlop, H.M.; Pushkaran, B.; Liggins, A.P.; Pulford, K.; Banham, A.H.; Pezzella, F.; Boultwood, J.; Wainscoat, J.S.; et al. Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Brit. J. Haematol. 2008, 141, 672–675, doi:10.1111/j.1365-2141.2008.07077.x.
[12]
Mitchell, P.S.; Parkin, R.K.; Kroh, E.M.; Fritz, B.R.; Wyman, S.K.; Pogosova-Agadjanyan, E.L.; Peterson, A.; Noteboom, J.; O'Briant, K.C.; Allen, A.; et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc. Natl. Acad. Sci. USA 2008, 105, 10513–10518, doi:10.1073/pnas.0804549105. 18663219
[13]
Mittra, I.; Nair, N.K.; Mishra, P.K. Nucleic acids in circulation: Are they harmful to the host? J. Biosci. 2012, 37, 301–312, doi:10.1007/s12038-012-9192-8. 22581336
[14]
Chen, X.; Ba, Y.; Ma, L.; Cai, X.; Yin, Y.; Wang, K.; Guo, J.; Zhang, Y.; Chen, J.; Guo, X.; et al. Characterization of microRNAs in serum: A novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008, 18, 997–1006, doi:10.1038/cr.2008.282. 18766170
[15]
Chim, S.S.C.; Shing, T.K.F.; Hung, E.C.W.; Leung, T.Y.; Lau, T.K.; Chiu, R.W.K.; Lo, Y.M.D. Detection and characterization of placental microRNAs in maternal plasma. Clin. Chem. 2008, 54, 482–490, doi:10.1373/clinchem.2007.097972. 18218722
[16]
Ma, R.; Jiang, T.; Kang, X. Circulating microRNAs in cancer: Origin, function and application. J. Exp. Clin. Cancer Res. 2012, 31, 38, doi:10.1186/1756-9966-31-38. 22546315
[17]
Zhang, C.; Wang, C.; Chen, X.; Yang, C.; Li, K.; Wang, J.; Dai, J.; Hu, Z.; Zhou, X.; Chen, L.; et al. Expression profile of microRNAs in serum: A fingerprint for esophageal squamous cell carcinoma. Clin. Chem. 2010, 56, 1871–1879, doi:10.1373/clinchem.2010.147553. 20943850
[18]
Zhang, T.; Wang, Q.; Zhao, D.; Cui, Y.; Cao, B.; Guo, L.; Lu, S.H. The oncogenetic role of microRNA-31 as a potential biomarker in oesophageal squamous cell carcinoma. Clin. Sci. 2011, 121, 437–447, doi:10.1042/CS20110207. 21658006
[19]
Komatsu, S.; Ichikawa, D.; Takeshita, H.; Tsujiura, M.; Morimura, R.; Nagata, H.; Kosuga, T.; Iitaka, D.; Konishi, H.; Shiozaki, A.; et al. Circulating microRNAs in plasma of patients with oesophageal squamous cell carcinoma. Br. J. Cancer 2011, 105, 104–111, doi:10.1038/bjc.2011.198. 21673684
[20]
Tsujiura, M.; Ichikawa, D.; Komatsu, S.; Shiozaki, A.; Takeshita, H.; Kosuga, T.; Konishi, H.; Morimura, R.; Deguchi, K.; Fujiwara, H.; et al. Circulating microRNAs in plasma of patients with gastric cancers. Br. J. Cancer 2010, 102, 1174–1179, doi:10.1038/sj.bjc.6605608. 20234369
[21]
Zhou, H.; Guo, J.M.; Lou, Y.R.; Zhang, X.J.; Zhong, F.D.; Jiang, Z.; Cheng, J.; Xiao, B.X. Detection of circulating tumor cells in peripheral blood from patients with gastric cancer using microRNA as a marker. J. Mol. Med. 2010, 88, 709–717, doi:10.1007/s00109-010-0617-2. 20349219
[22]
Liu, R.; Zhang, C.; Hu, Z.; Li, G.; Wang, C.; Yang, C.; Huang, D.; Chen, X.; Zhang, H.; Zhuang, R.; et al. A five-microRNA signature identified from genome-wide serum microRNA expression profiling serves as a fingerprint for gastric cancer diagnosis. Eur. J. Cancer 2011, 47, 784–791, doi:10.1016/j.ejca.2010.10.025. 21112772
[23]
Liu, H.; Zhu, L.; Liu, B.; Yang, L.; Meng, X.; Zhang, W.; Ma, Y.; Xiao, H. Genome-wide microRNA profiles identify miR-378 as a serum biomarker for early detection of gastric cancer. Cancer Lett. 2012, 316, 196–203, doi:10.1016/j.canlet.2011.10.034. 22169097
[24]
Konishi, H.; Ichikawa, D.; Komatsu, S.; Shiozaki, A.; Tsujiura, M.; Takeshita, H.; Morimura, R.; Nagata, H.; Arita, T.; Kawaguchi, T.; et al. Detection of gastric cancer-associated microRNAs on microRNA microarray comparing pre- and post-operative plasma. Br. J. Cancer 2012, 106, 740–747, doi:10.1038/bjc.2011.588. 22262318
[25]
Song, M.Y.; Pan, K.F.; Su, H.J.; Zhang, L.; Ma, J.L.; Li, J.Y.; Yuasa, Y.; Kang, D.; Kim, Y.S.; You, W.C. Identification of serum microRNAs as novel non-invasive biomarkers for early detection of gastric cancer. PLoS One 2012, 7, e33608, doi:10.1371/journal.pone.0033608. 22432036
[26]
Wang, M.; Gu, H.; Wang, S.; Qian, H.; Zhu, W.; Zhang, L.; Zhao, C.; Tao, Y.; Xu, W. Circulating miR-17-5p and miR-20a: Molecular markers for gastric cancer. Mol. Med. Report. 2012, 5, 1514–1520. 22406928
[27]
Wang, J.; Chen, J.; Chang, P.; LeBlanc, A.; Li, D.; Abbruzzesse, J.L.; Frazier, M.L.; Killary, A.M.; Sen, S. MicroRNAs in plasma of pancreatic ductal adenocarcinoma patients as novel blood-based biomarkers of disease. Cancer Prev. Res. 2009, 2, 807–813, doi:10.1158/1940-6207.CAPR-09-0094.
[28]
Kong, X.; Du, Y.; Wang, G.; Gao, J.; Gong, Y.; Li, L.; Zhang, Z.; Zhu, J.; Jing, Q.; Qin, Y.; et al. Detection of differentially expressed microRNAs in serum of pancreatic ductal adenocarcinoma patients: MiR-196a could be a potential marker for poor prognosis. Dig. Dis. Sci. 2011, 56, 602–609, doi:10.1007/s10620-010-1285-3. 20614181
[29]
Liu, J.; Gao, J.; Du, Y.; Li, Z.; Ren, Y.; Gu, J.; Wang, X.; Gong, Y.; Wang, W.; Kong, X. Combination of plasma microRNAs with serum CA19-9 for early detection of pancreatic cancer. Int. J. Cancer 2011, 131, 683–691. 21913185
[30]
Morimura, R.; Komatsu, S.; Ichikawa, D.; Takeshita, H.; Tsujiura, M.; Nagata, H.; Konishi, H.; Shiozaki, A.; Ikoma, H.; Okamoto, K.; et al. Novel diagnostic value of circulating miR-18a in plasma of patients with pancreatic cancer. Br. J. Cancer 2011, 105, 1733–1740, doi:10.1038/bjc.2011.453. 22045190
[31]
Liu, R.; Chen, X.; Du, Y.; Yao, W.; Shen, L.; Wang, C.; Hu, Z.; Zhuang, R.; Ning, G.; Zhang, C.; et al. Serum MicroRNA Expression profile as a biomarker in the diagnosis and prognosis of pancreatic cancer. Clin. Chem. 2012, 58, 610–618, doi:10.1373/clinchem.2011.172767. 22194634
[32]
Yamamoto, Y.; Kosaka, N.; Tanaka, M.; Koizumi, F.; Kanai, Y.; Mizutani, T.; Murakami, Y.; Kuroda, M.; Miyajima, A.; Kato, T.; et al. MicroRNA-500 as a potential diagnostic marker for hepatocellular carcinoma. Biomarkers 2009, 14, 529–538, doi:10.3109/13547500903150771. 19863192
[33]
Gui, J.; Tian, Y.; Wen, X.; Zhang, W.; Zhang, P.; Gao, J.; Run, W.; Tian, L.; Jia, X.; Gao, Y. Serum microRNA characterization identifies miR-885-5p as a potential marker for detecting liver pathologies. Clin. Sci. 2011, 120, 183–193, doi:10.1042/CS20100297. 20815808
[34]
Li, L.M.; Hu, Z.B.; Zhou, Z.X.; Chen, X.; Liu, F.Y.; Zhang, J.F.; Shen, H.B.; Zhang, C.Y.; Zen, K. Serum microRNA profiles serve as novel biomarkers for HBV infection and diagnosis of HBV-positive hepatocarcinoma. Cancer Res. 2010, 70, 9798–9807, doi:10.1158/0008-5472.CAN-10-1001. 21098710
[35]
Xu, J.; Wu, C.; Che, X.; Wang, L.; Yu, D.; Zhang, T.; Huang, L.; Li, H.; Tan, W.; Wang, C.; et al. Circulating microRNAs, miR-21, miR-122, and miR-223, in patients with hepatocellular carcinoma or chronic hepatitis. Mol. Carcinog. 2011, 50, 136–142, doi:10.1002/mc.20712. 21229610
[36]
Qu, K.Z.; Zhang, K.; Li, H.; Afdhal, N.H.; Albitar, M. Circulating microRNAs as biomarkers for hepatocellular carcinoma. J. Clin. Gastroenterol. 2011, 45, 355–360, doi:10.1097/MCG.0b013e3181f18ac2. 21278583
[37]
Zhou, J.; Yu, L.; Gao, X.; Hu, J.; Wang, J.; Dai, Z.; Wang, J.F.; Zhang, Z.; Lu, S.; Huang, X.; et al. Plasma microRNA panel to diagnose hepatitis B virus-related hepatocellular carcinoma. J. Clin. Oncol. 2011, 29, 4781–4788, doi:10.1200/JCO.2011.38.2697. 22105822
[38]
Qi, P.; Cheng, S.Q.; Wang, H.; Li, N.; Chen, Y.F.; Gao, C.F. Serum microRNAs as biomarkers for hepatocellular carcinoma in Chinese patients with chronic hepatitis B virus infection. PLoS One 2011, 6, e28486, doi:10.1371/journal.pone.0028486. 22174818
[39]
Li, J.; Wang, Y.; Yu, W.; Chen, J.; Luo, J. Expression of serum miR-221 in human hepatocellular carcinoma and its prognostic significance. Biochem. Biophys. Res. Commun. 2011, 406, 70–73, doi:10.1016/j.bbrc.2011.01.111. 21295551
[40]
Ng, E.K.; Chong, W.W.; Jin, H.; Lam, E.K.; Shin, V.Y.; Yu, J.; Poon, T.C.; Ng, S.S.; Sung, J.J. Differential expression of microRNAs in plasma of patients with colorectal cancer: A potential marker for colorectal cancer screening. Gut 2009, 58, 1375–1381, doi:10.1136/gut.2008.167817. 19201770
[41]
Huang, Z.; Huang, D.; Ni, S.; Peng, Z.; Sheng, W.; Du, X. Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer. Int. J. Cancer 2010, 127, 118–126, doi:10.1002/ijc.25007. 19876917
[42]
Wang, L.G.; Gu, J. Serum microRNA-29a is a promising novel marker for early detection of colorectal liver metastasis. Cancer Epidem. 2012, 36, e61–e67, doi:10.1016/j.canep.2011.05.002.
[43]
Cheng, H.; Zhang, L.; Cogdell, D.E.; Zheng, H.; Schetter, A.J.; Nykter, M.; Harris, C.C.; Chen, K.; Hamilton, S.R.; Zhang, W. Circulating plasma miR-141 is a novel biomarker for metastatic colon cancer and predicts poor prognosis. PLoS One 2011, 6, e17745, doi:10.1371/journal.pone.0017745. 21445232
[44]
Pu, X.X.; Huang, G.L.; Guo, H.Q.; Guo, C.H.; Li, H.; Ye, S.; Ling, S.; Jiang, L.; Tian, Y.; Lin, T.Y. Circulating miR-221 directly amplified from plasma is a potential diagnostic and prognostic marker of colorectal cancer and is correlated with p53 expression. J. Gastroenterol. Hepatol. 2010, 25, 1674–1680, doi:10.1111/j.1440-1746.2010.06417.x. 20880178
[45]
Weber, J.A.; Baxter, D.H.; Zhang, S.; Huang, D.Y.; Huang, K.H.; Lee, M.J.; Galas, D.J.; Wang, K. The microRNA spectrum in 12 body fluids. Clin. Chem. 2010, 56, 1733–1741, doi:10.1373/clinchem.2010.147405. 20847327
[46]
Link, A.; Balaguer, F.; Shen, Y.; Nagasaka, T.; Lozano, J.J.; Boland, C.R.; Goel, A. Fecal MicroRNAs as novel biomarkers for colon cancer screening. Cancer Epidem. Biomark. Prev. 2010, 19, 1766–1774, doi:10.1158/1055-9965.EPI-10-0027.
[47]
Hanke, M.; Hoefig, K.; Merz, H.; Feller, A.C.; Kausch, I.; Jocham, D.; Warnecke, J.M.; Sczakiel, G. A robust methodology to study urine microRNA as tumor marker: MicroRNA-126 and microRNA-182 are related to urinary bladder cancer. Urol. Oncol. 2010, 28, 655–661, doi:10.1016/j.urolonc.2009.01.027. 19375957
[48]
Hanson, E.K.; Lubenow, H.; Ballantyne, J. Identification of forensically relevant body fluids using a panel of differentially expressed microRNAs. Anal. Biochem. 2009, 387, 303–314, doi:10.1016/j.ab.2009.01.037. 19454234
