|
Diagnostic Potential of Circulating MicroRNA-21 in Hepatocellular Carcinoma.
[Full Text]
AUTHOR(S)
Waleed Alnoanmany, Hisham A Ismail, Hala El-said, Manar Obada , Mostafa A Sakr , Ashraf Y Elfert
KEYWORDS
Key words: Hepatocellular Carcinoma – MiRNA-21– PTEN – AFP.
ABSTRACT
Abstract—
Background & Aims
Several studies have reported the significance of circulating microRNA as a biochemical marker of cancer. However, there are no reports on the significance of circulating microRNA in hepatocellular carcinoma. The aim of this study was to evaluate the significance of plasma microRNA-21 level as a biochemical marker for hepatocellular carcinoma.
Materials & Methods: To identify the causal role of (MicroRNA-21) in hepatocarcinogenesis we used a human model in which 30 diagnosed HCC cases of different stages, 20 HCV positive cases and 20 healthy controls were tested for circulating microRNA-21 using whole blood samples taken from mentioned individuals at National Liver Institute Menoufiya University. MicroRNA extraction, Amplification RT-PCR was done for all samples with other various biochemical analysis.
Results: Real-time RT-PCR analysis demonstrated upregulation of oncogenic miR-21 at different stages of hepatocarcinogenesis. On the other hand, there were no significant miRNA-21 changes neither in HCV nor Control groups. ROC study showed that the best cutoff value for miR-21 was 3.93 (Fold expression) and the sensitivity was 93 % while the specificity was 90%. Compared to the cutoff value for AFP which was 91.7 (ng/mL) and the sensitivity was 75.2 % while the specificity was 92.3 %.
Conclusion: Circulating MiRNA-21 level is more sensitive than AFP and highly specific as a biological marker for HCC, also it is proved to be beneficial in early diagnosis of HCC.
Targeting of microRNA-21 is sufficient to limit tumor cell proliferation and invasion in a manner that is likely to involve associated changes in multiple targets, suggesting that suppression of microRNA-21 may be an approach for the treatment of hepatocellular carcinoma.
REFERENCES
[1] El-Serag HB and Davila JA. Surveillance for hepatocellularcarcinoma:in whom and how?. Therap Adv Gastroenterol 2011; 4: 5–10.
[2] El-Zayadi AR, Badran HM, Barakat EM, Attia M, Shawky S and Mohamed MK. Hepatocellular carcinoma in Egypt: a single center study over a decade. World J Gastroenterol 2005; 11: 5193–5198.
[3] Ikeda M, Fujiyama S, Tanaka M, Sata M, Ide T, Yatsuhashi H and Watanabe H. Risk factors for development of hepatocellular carcinoma in patients with chronic hepatitis C after sustained response to interferon. J Gastroenterol 2005; 40: 148–156.
[4] Degos F, Christidis C, Ganne-Carrie N, Farmachidi JP, Degott C and Guettier C. Hepatitis C virus related cirrhosis (time to occurrence of hepatocellular carcinoma and death). Gut 2000; 47:131–136.
[5] Ebert, M.S. Sharp and P.A. Roles for microRNAs in conferring robustness to biological processes. Cell 2012; 149, 515–524.
[6] Kozomara A, Griffiths-Jones and S. miRBase. Integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res 2011; 39, D152–D157.
[7] Negrini M, Gramantieri L, Sabbioni S and Croce C.M. microRNA involvement in hepatocellular carcinoma. Anticancer Agents Med. Chem 2008; 11, 500–521.
[8] Law, P.T and Wong, N. Emerging roles of microRNA in the intracellular signaling networks of hepatocellular carcinoma. J. Gastroenterol. Hepatol 2011; 26, 437–439.
[9] Aravalli R.N, Cressman E.N and Steer C.J. Cellular and molecular mechanisms of hepatocellular carcinoma: An update. Arch. Toxicol 2012 ; 87, 227–247.
[10] Datta J, Kutay H, Nasser M.W, Nuovo G.J, Wang B, Majumder S et al. Methylation mediated silencing of MicroRNA-1 gene and its role in hepatocellular carcinogenesis. Cancer Res 2008; 68, 5049–5058.
[11] Wan XW, Jiang M, Cao HF, He YQ, Liu SQ, Qiu XH et al. The alteration of PTEN tumor suppressor expression and its association with the histopathological features of human primary hepatocellular carcinoma. J Cancer Res Clin Oncolology 2013; 129: 100 –106.
[12] Esau C, Davis S, Murray SF, Yu XX, Pandey SK, Pear M et al. MiR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metabolism 2009; 3:87–98.
[13] Krutzfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Mano- haran M et al. Silencing of microRNAs in vivo with ‘an- tagomirs’. Nature 2005; 438:685–689.
[14] Itoh S, Maeda T, Shimada M, Aishima S, Shirabe K, Tanaka S et al. Role of expression of focal adhesion kinase in pro- gression of hepatocellular carcinoma. Clin Cancer Res 2014; 10: 2812–2817.
[15] Esquela-Kerscher A and Slack FJ. Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer 2006; 6:259 –269.
[16] Horie Y, Suzuki A, Kataoka E, Sasaki T, Hamada K, Sasaki J et al. Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular car- cinomas. J Clin Invest 2004; 113:1774 –1783.
[17] Hu TH, Huang CC, Lin PR, Chang HW, Ger LP, Lin YW et al. Expression and prognostic role of tumor suppressor gene PTEN/MMAC1/TEP1 in hepatocellular carcinoma. Cancer 2003; 97:1929–1940.
[18] Zhang JG, Wang JJ, Zhao F, Liu Q, Jiang K and Yang GH. MicroRNA-21 (miR-21) represses tumor suppressor PTEN and promotes growth and invasion in non-small cell lung cancer (NSCLC).Clin Chim Acta 2010; 41:846-52.
[19] Fanyin Meng, Roger Henson, Hania Wehbe–Janek, Kalpana Ghoshal, Samson T Jacob and Tushar Patel MicroRNA-21 Regulates Expression of the PTEN Tumor Suppressor Gene in Human Hepatocellular Cancer. Gastroentrol 2007; 12:133-2.
[20] Qibin Liao, Peiyu Han, Yue Huang, Zhitong Wu, Qing Chen, Shanshan Li et al. Potential Role of Circulating microRNA-21 for Hepatocellular Carcinoma Diagnosis:A Meta-Analysis. PLoS One 2015; 10(6): e0130677.
[21] Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, 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.
[22] Tomimaru Y, Eguchi H, Nagano H, Wada H and Kobayashi S. Circulating microRNA-21 as a novel biomarker for hepatocellular carcinoma. J Hepatol 2012; 56:167–75.
[23] Corvallis AH. Early diagnosis of hepatocellular carcinoma by microRNAs: shining a light from the genome’s “dark matter”. Dig Dis Sci 2012; 57:2737–2739.
[24] Haraguchi T, Haruo N, Takanobu N, Tokimitsu O, Youshihito U, testsuo Y et al. A potent 2’-O-methylated RNA-based microRNA inhibitor with unique secondary structures. Nucleic Acids Res 2012; 40:58-123.
|
