POSSIBLE DIAGNOSTIC AND PROGNOSTIC ROLE OF microRNA-122 IN HEPATOCELLULAR CARCINOMA
Abstract
Background and objectives: The sensitivity and specificity of the available biomarkers for the diagnosis of hepatocellular carcinoma (HCC) are inadequate. Consequently, there is a need to create trustworthy biomarkers that are sensitive, specific, and non-invasive for HCC early detection and quick management to boost patient survival rates. Circulatory miRNAs have received a lot of attention recently as potential non-invasive biomarkers for a number of illnesses. Their expression patterns reflect the state of the illness and/or the degree of therapeutic response, and they remain remarkably stable in blood. In order to improve patient prognosis, the goal of this study was to analyze the expression profile of miRNA-122 in HCC patients and to evaluate their clinical value as novel HCC prognostic indicators as early as practical. Methodology: There were 150 Egyptian patients in this prospective case-control study, 50 with liver cirrhosis (LC), 50 had HCC, and 50 of whom were healthy. The miR-122 was measured using reverse transcription (RT) real-time PCR. Results: HCC had considerably lower levels of miR-122 than the other two studied groups. MiR-122 distinguished HCC patients from healthy controls with a specificity and sensitivity of 96.0% against 82.0%, respectively AUC= 0.903, according to an examination of receiver operating characteristic curves. AUC=0.849 revealed a specificity and sensitivity of 74.0% and 82.0% respectively to distinguish cirrhotic patients from HCC participants. Univariate analysis of miR-122 affecting mortality was observed in this study. Conclusions: Expression of miR-122 decreased in HCC patients can be used to differentiate HCC from LC. MicroRNA-122 may be utilized as early, non-invasive indicators for both diagnosis and prognosis of HCC.
References
Ahmed T., Ahmad E. Ibrahim and Saeed A. M., (2020). Serum mirna-122 as a diagnostic marker in HCV related liver cirrhosis. Afro-Egyptian Journal of Infectious and Endemic Diseases, 10(4): 335-345. doi: 10.21608/aeji.2020. 30137 .1082.
Callegari E., Gramantieri L., Domenicali M., D'Abundo L., Sabbioni S. and Negrini M., (2015). MicroRNAs in liver cancer: a model for investigating pathogenesis and novel therapeutic approaches. Cell Death Differ., 22(1):46-57. doi: 10.1038/cdd.2014.136.
Dhanasekaran R., Bandoh S. and Roberts L. R., (2016). Molecular pathogenesis of hepatocellular carcinoma and impact of therapeutic advances. F1000Res.;5:F1000 Faculty Rev-879. doi: 10.12688/f1000 research.6946.1.
Dorgalaleh A., Favaloro E. J., Bahraini M. and Rad F., (2021). Standardization of Prothrombin Time/International Normalized Ratio (PT/INR). Int J. Lab. Hematol., 43(1):21-28. doi: 10.1111/ijlh.13349.
El-Ahwany E. G. E., Mourad L., Zoheiry M. M. K., Abu-Taleb H., Hassan M., Atta R., Hassanien M. and Zada S., (2019). MicroRNA-122a as a non-invasive biomarker for HCV genotype 4-related hepatocellular carcinoma in Egyptian patients. Arch Med Sci. 2019, 15(6):1454- 1461. doi: 10.5114/aoms.2019.86621.
El-Tonsy M. M., Hussein H. M., Helal Tel-S., Tawfik R. A., Koriem K. M. and Hussein H. M., (2016). Human Schistosomiasis mansoni associated with hepatocellular carcinoma in Egypt: current perspective. J Parasit Dis., 40(3):976-80. doi: 10.1007/s12639-014-0618-0.
Fawzy Montaser M., Amin Sakr M. and Omar Khalifa M., (2012). Alpha-L-fucosidase as a tumour marker of hepatocellular carcinoma. Arab J Gastroenterol., 13(1):9-13. doi: 10.1016/j.ajg.2012.03.006.
Franck M., Schütte K., Malfertheiner P. and Link A., (2020). Prognostic value of serum microRNA-122 in hepatocellular carcinoma is dependent on coexisting clinical and laboratory factors. World J. Gastroenterol., 26(1):86-96. doi: 10.3748/wjg. v26.i1.86.
Fu X. and Calin G. A., (2018). miR-122 and hepatocellular carcinoma: from molecular biology to therapeutics. EBioMedicine., 37:17-18. doi: 10.1016/j.ebiom.2018.10.032.
Fukuhara T. and Matsuura Y., (2013). Role of miR-122 and lipid metabolism in HCV infection. J Gastroenterol. 2013; 48:169-76.
Gani R. A., (2017). Hepatocellular Carcinoma (HCC) surveillance: comprehensive management in liver cirrhosis patients Indones. J. Gastroenterol. Hepatol. Dig. Endosc., 18, pp. 137-139.
Hsu C. Y., Lee Y. H., Huang Y. H., Hsia C. Y., Su C. W., Lin H. C. and Lee S. D., (2013). Ascites in patients with hepatocellular carcinoma: prevalence, associated factors, prognostic impact, and staging strategy. Hepatology international., 7(1):88-198.
Huang Y., Chen Y., Tu S., Zhang J., Qiu Y. and Yu W., (2022). Diagnostic accuracy of circulating microRNAs for hepatitis C virus-associated hepatocellular carcinoma: a systematic review and meta-analysis. BMC Infect Dis., 22(1):323. doi: 10.1186/s 12879-022-07292-8.
Huang A., Yang X. R., Chung W. Y., Dennison A. R. and Zhou J., (2020). Targeted therapy for hepatocellular carcinoma. Signal Transduct Target Ther, 5(1):1-13.
Keng V. W., Largaespada D. A. and Villanueva A., (2012). Why men are at higher risk for hepatocellular carcinoma? J. Hepatol., 57(2):453- 4. doi: 10.1016/j.jhep. 03.004.
Khasraghi L.B., Nouri M., Vazirzadeh M., Hashemipour N., Talebi M. and Zarch F.A., (2023). MicroRNA-206 in human cancer: mechanistic and clinical perspectives. Cell Signal., 101:110525.
Kwo P. Y., Cohen S. M. and Lim J. K., (2017). ACG Clinical Guideline: Evaluation of Abnormal Liver Chemistries. Am J Gastroenterol., 112(1):18-35. doi: 10.1038 /ajg. 2016.517.
Liu K., Huang Z., Yang S., Lin L., Zheng S., Zhang X., Xue Y. and Xie W., (2022). The Age, Gamma- Glutamyl Transpeptidase and Platelet Index: A Novel Noninvasive Model for Predicting Hepatocellular Carcinoma in Patients with Hepatitis B Virus-Related Liver Cirrhosis. J. Hepatocell Carcinoma., 9:1057-1063. doi: 10.2147/JHC.S386977.
Llovet J. M., Kelley R. K., Villanueva A., Singal A. G, Pikarsky E., Roayaie S., Lencioni R., Koike K., Zucman-Rossi J. and Finn R. S., (2021). Hepatocellular carcinoma. Nat Rev Dis Primers., 21;7(1):6. doi: 10.1038/s41572-020-00240-3.
Ma H. Y., Dong L., Quan S. Z., Li R. Y. and Wang X. R., (2021). Comparison of four markers of hepatic fibrosis and hepatic function indices in patients with liver cirrhosis and hepatoma. Ann Palliat Med., 10(4):4108-4121. doi: 10.21037/apm-20-1623.
Morishita A., Oura K., Tadokoro T., Fujita K., Tani J. and Masaki T., (2021). MicroRNAs in the Pathogenesis of Hepatocellular Carcinoma: A Review. Cancers (Basel)., 13 (3):514. doi: 10.3390 /cancers13030514.
Nah E.H., Kim S., Cho S. and Cho H. I., (2018). Complete Blood Count Reference Intervals and Patterns of Changes Across Pediatric, Adult, and Geriatric Ages in Korea. Ann Lab Med., 38(6):503-511. doi: 10.3343/alm.2018.38.6.503.
Oura K., Morishita A. and Masaki T., (2020). Molecular and Functional Roles of MicroRNAs in the Progression of Hepatocellular Carcinoma-A Review. Int J. Mol. Sci., 21(21):8362. doi: 10.3390 /ijms21218362.
Pan C., Wang X., Shi K., Zheng Y., Li J., Chen Y., Jin L. and Pan Z., (2016). MiR-122 Reverses the Doxorubicin-Resistance in Hepatocellular Carcinoma Cells through Regulating the Tumor Metabolism. PLoS One., 11(5): e0152090. doi: 10.1371/ journal.pone.0152090.
Parizadeh S. M., Jafarzadeh-Esfehani R., Ghandehari M., Goldani F., Parizadeh S. M., Hassanian S. M. and Ghayour-Mobarhan M., (2019). MicroRNAs as potential diagnostic and prognostic biomarkers in hepatocellular carcinoma. Current Drug Targets, 20 (11):1129-1140.
Ringelhan M., Pfister D., O'Connor T., Pikarsky E. and Heikenwalder M., (2018). The immunology of hepatocellular carcinoma. Nat Immunol., 19(3):222-232. doi: 10.1038/s41590-018-0044-z.
Sarin S. K., Kumar M., Eslam M., George J., Al Mahtab M. and Akbar S. M. F., (2020). Liver diseases in the Asia-Pacific region: a Lancet Gastroenterology & Hepatology Commission. Lancet Gastroenterol Hepatol., 5(2):167-228. doi: 10. 1016/S2468-1253(19)30342-5.
Shaker O., Mahfouz H., Salama A. and Medhat E., (2020). Long Non-Coding HULC and miRNA-372 as Diagnostic). Biomarkers in Hepatocellular Carcinoma. Rep Biochem Mol Biol., 9(2):230-240. doi: 10.29252/rbmb.9.2.230.
Shehab-Eldeen S., Nada A.and Abou-Elela D., (2019). Diagnostic performance of microRNA-122 and microRNA-224 in hepatitis C virus-induced hepatocellular carcinoma (HCC). Asian Pac J Cancer Prev., 20: 2515-2522.
Shirvani H., Ghanavi J., Aliabadi A., Mousavinasab F., Talebi M. and Majidpoor J., (2023). MiR-211 plays a dual role in cancer development: from tumor suppressor to tumor enhancer. Cell Signal., 101:110504.
Siegel R. L., Miller K. D., Fuchs H. E. and Jemal A., (2022). Cancer statistics, 2022. CA Cancer J. Clin., 72(1):7- 33. doi: 10.3322/caac.21708.
Singal A. G., Lampertico P. and Nahon P., (2020). Epidemiology and surveillance for hepatocellular carcinoma: New trends. J. Hepatol., 72(2):250- 261. doi: 10.1016/j. jhep.2019.08.025.
Szabo G. and Bala S., (2013). MicroRNAs in liver disease. Nat. Rev. Gastroenterol Hepatol., 10:542-52.
Tapper E. B., Saini S. D. and Sengupta N., (2017). Extensive testing or focused testing of patients with elevated liver enzymes. J. Hepatol., 66(2):313-319. doi: 10.1016/j. jhep.2016.09.017.
Wang S., Qiu L., Yan X., Jin W., Wang Y., Chen L., Wu E., Ye X., Gao G. F., Wang F., Chen Y., Duan Z. and Meng S., (2012). Loss of microRNA 122 expression in patients with hepatitis B enhances hepatitis B virus replication through cyclin G (1) -modulated P53 activity. Hepatology., 55:730-41.
Xiang Z., Wu J., Li J., Zheng S., Wei X. and Xu X., (2023). Gut microbiota modulation: a viable strategy to address medical needs in hepatocellular carcinoma and liver transplantation. Engineering. doi: 10.1016/j.eng. 2022.12.012
Yamamoto Y., Kondo S., Matsuzaki J., Esaki M., Okusaka T. and Shimada K., (2019). Highly Sensitive Circulating MicroRNA Panel for Accurate Detection of Hepatocellular Carcinoma in Patients With Liver Disease. Hepatol Commun., 4(2):284-297. doi: 10.1002/hep4.1451.
Yerukala Sathipati S. snd Ho S-Y., (2020). Novel miRNA signature for predicting the stage of hepatocellular carcinoma. Scientific reports., 10(1):1-12. 14452. doi: 10.1038/s41598-020-71324-z
Zhan G., Jiang H., Yang R. and Yang K., (2021). miR-122 and miR-197 expressions in hepatic carcinoma patients before and after chemotherapy and their effect on patient prognosis. Am J. Transl Res., 13(6):6731-6737.
Zhao XF., Li N., Lin D. D. and Sun L. B., (2020). Circulating MicroRNA-122 for the Diagnosis of Hepatocellular Carcinoma: A Meta-Analysis. Biomed Res. Int., 2020:5353695. doi: 10.1155 /2020/5353695.
