Cluster of specified microRNAs in tissues and serum as biomarkers for early diagnosis of hepatocellular carcinoma.

Objective: Hepatocellular carcinoma (HCC) is a global public health concern that lacks efficient methods for early diagnosis. Accumulated evidence has revealed great potential using microRNAs (miRNAs) as noninvasive biomarkers in HCC detection.

Methods: Serum miRNAs (miR21, miR122, miR-214, miR15b, and let-7f) were detected in 75 patients with HCC and 80 healthy controls (HC). In addition, 75 HCC tissues and paired normal adjacent tissues were also analyzed for comparison. Quantified by real-time quantitative RT-PCR was used to evaluate the expression of miRNAs.

Results: We discovered significant up-regulation of miR-21 (P < 0.001) and miR-15b (P < 0.001) as well as a down-regulation of miR-122 (P = 0.01) in HCC tissues compared to adjacent non-tumor tissues. Additionally, miR-21 (P < 0.001) and miR-15b (P < 0.001) levels were upregulated in serum and miR-214 (P = 0.01) was decreased in HCC patients compared to that in healthy controls. Multivariate logistic regression analysis showed that serum miR-21 (OR = 1.68, P = 0.012) and miR-15b (OR = 1.736, = 0.012) were independently associated with HCC whereas miR-214 (OR = 0.631, = 0.006) was associated with a decreased risk of HCC. When we employed miR-(21 + 122 + 15b) classifier as biomarkers, we could discriminate HCC tissues from adjacent non-tumor tissues with an AUC of 0.885 (specificity: 89.7%; sensitivity: 73.1%). In serum, the cluster of miR-(21 + 214 + 15b) classifier (AUC = 0.887) had a sensitivity of 80.3% and a specificity of 87.0% for HCC diagnosis.

Conclusion: Our results suggest that these serum miRNAs may be useful markers for discriminating HCC patients from healthy controls. Combined determination of circulating miR-21, miR-122, miR-214, and miR-15b has great potential to serve as an accurate and noninvasive biomarker for the early HCC preliminary screening.