Circulating microRNAs (miR-16, miR-22, miR-122) expression and early diagnosis of hepatocellular carcinoma

Purpose: Circulating microRNA (miRNA) has been reported to have diagnostic value in multiple tumors. To identify serum miRNAs for early diagnosis of hepatocellular carcinoma (HCC), we analyzed the differential miRNA expression between HCC patients and controls.
Methods: Real-time reverse transcription polymerase chain reaction (RT-PCR) was carried out to detect serum miR-16, miR-22, and miR-122 expression in 100 HCC patients and 100 controls (including hepatitis B, liver cirrhosis, liver metastases, hepatic hemangioma, health group, and each of them had 20 subjects). The miRNA expression results were combined with alpha-fetoprotein (AFP) to evaluate the diagnostic efficacy in HCC through receiver operating characteristic (ROC) curve. And the target genes were predicted through bioinformatics methods.
Results: Compared with controls, the expression of miR-16 and miR-122 significantly increased in early-stage HCC patients, while no significant changes were detected in miR-22. The ROC curve analysis demonstrated that miR-16 and miR-122 had a high diagnostic efficacy (AUC 0.798 and 0.759), and it was improved when combined with AFP (AUC 0.862). When compared with each of the five groups in the controls, the results showed that miR-16 of HCC was significantly higher than liver cirrhosis (AUC 0.936), liver metastases, and health; miR-122 was significantly higher than liver metastases, hepatitis B, and health. Moreover, 175 and 101 potential target genes were regulated by miR-16 and miR-122, respectively. And most of the target genes were enriched in the PI3K, MAPK, FoxO signaling pathways, and pathways in cancer.
Conclusion: Our findings illustrate that both circulating miR-16 and miR-122 can provide value for early diagnosis of HCC and they are potential biomarkers for the early-stage HCC.