The aim of this study was to explore the diagnostic and prognostic value of serum microRNAs (miRNAs) in hepatitis B viral (HBV)-related hepatocellular carcinoma (HCC). We retrospectively analyzed clinical data of 84 consecutive patients with HBV-related HCC who underwent curative resection. Additionally, we enrolled 46 healthy controls and 31 patients with chronic liver disease (CLD). Serum levels of miR-155-5p, miR-24-3p, miR-490-3p, miR-210-3p, and miR-335-5p were measured. Associations of serum miRNAs with clinicopathological factors were evaluated. Receiver operating characteristic curves were established for discriminating HCC patients from CLD patients, and the area under the curve (AUC) was calculated. Overall survival (OS) and disease-free survival (DFS) were examined by the Kaplan–Meier method. Prognostic factors were determined by multivariate Cox analysis. Consequently, serum miR-24-3p levels were significantly greater in HCC patients than healthy controls and CLD patients. Serum miR-24-3p was significantly associated with vascular invasion in HCC patients. Serum miR-24-3p discriminated HCC patients from CLD, with an AUC of 0.636 [95 % confidence interval (CI) 0.524–0.748]. Combined serum alpha-fetoprotein (AFP) and miR-24-3p had an increased AUC of 0.834 (95 % CI 0.745–0.923; P < 0.001). Elevated serum miR-24-3p was an independent poor prognostic factor for OS and DFS of HCC patients. In conclusion, the combination of serum miR-24-3p and AFP improves the diagnostic accuracy for HCC prediction compared to each biomarker alone. High serum miR-24-3p level is an independent predictor of poor OS and DFS in patients with HBV-related HCC.
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This work was partly supported by the National Natural Science Foundation of China (Nos. 81201906 and 81172364) and Key Research Project of Anhui Provincial Health Department (No. 2010A006).
Conflict of interest
The authors declare that they have no competing financial interests.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.PubMedCrossRefGoogle Scholar
Venook AP, Papandreou C, Furuse J, de Guevara LL. The incidence and epidemiology of hepatocellular carcinoma: a global and regional perspective. Oncologist. 2010;15(Suppl 4):5–13.PubMedCrossRefGoogle Scholar
Abdalla MA, Haj-Ahmad Y. Promising candidate urinary MicroRNA biomarkers for the early detection of hepatocellular carcinoma among high-risk hepatitis C virus Egyptian patients. J Cancer. 2012;3:19–31.PubMedCrossRefPubMedCentralGoogle Scholar
Valencia-Sanchez MA, Liu J, Hannon GJ, Parker R. Control of translation and mRNA degradation by miRNAs and siRNAs. Genes Dev. 2006;20:515–24.PubMedCrossRefGoogle Scholar
Ying Q, et al. Hypoxia-inducible microRNA-210 augments the metastatic potential of tumor cells by targeting vacuole membrane protein 1 in hepatocellular carcinoma. Hepatology. 2011;54:2064–75.PubMedCrossRefGoogle Scholar
Zhang LY, Liu M, Li X, Tang H. miR-490-3p modulates cell growth and epithelial to mesenchymal transition of hepatocellular carcinoma cells by targeting endoplasmic reticulum-Golgi intermediate compartment protein 3 (ERGIC3). J Biol Chem. 2013;288:4035–47.PubMedCrossRefPubMedCentralGoogle Scholar
Huang S, et al. Upregulation of miR-23a approximately 27a approximately 24 decreases transforming growth factor-beta-induced tumor-suppressive activities in human hepatocellular carcinoma cells. Int J Cancer. 2008;123:972–8.PubMedCrossRefGoogle Scholar
Kroh EM, Parkin RK, Mitchell PS, Tewari M. Analysis of circulating microRNA biomarkers in plasma and serum using quantitative reverse transcription-PCR (qRT-PCR). Methods. 2010;50:298–301.PubMedCrossRefPubMedCentralGoogle Scholar
Lawrie CH, et al. Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol. 2008;141:672–5.PubMedCrossRefGoogle Scholar
Du WW, et al. MicroRNA miR-24 enhances tumor invasion and metastasis by targeting PTPN9 and PTPRF to promote EGF signaling. J Cell Sci. 2013;126:1440–53.PubMedCrossRefGoogle Scholar
Li A, et al. MicroRNA array analysis finds elevated serum miR-1290 accurately distinguishes patients with low-stage pancreatic cancer from healthy and disease controls. Clin Cancer Res. 2013;19:3600–10.PubMedCrossRefPubMedCentralGoogle Scholar
Franchina T, et al. Circulating miR-22, miR-24 and miR-34a as novel predictive biomarkers to pemetrexed-based chemotherapy in advanced non-small cell lung cancer. J Cell Physiol. 2014;229:97–9.PubMedGoogle Scholar
Liu YX, et al. MicroRNA-24 modulates aflatoxin B1-related hepatocellular carcinoma prognosis and tumorigenesis. Biomed Res Int. 2014;2014:482926.PubMedPubMedCentralGoogle Scholar