Development of a novel panel based on micro-RNAs (21, 29a, 200 and 335) and alpha-fetoprotein as diagnostic biomarkers for hepatocellular carcinoma associated with hepatitis C infection.

BACKGROUND AND STUDY AIMS

MicroRNAs (miRNAs) play key roles in cancer biology; they are used as potential tools in cancer diagnosis. This study investigated the microRNA expression profile of patients with hepatocellular carcinoma (HCC).

PATIENTS AND METHODS

Serum microRNA expression profiles (miRNA-29a, miRNA-200, miRNA-335 and miRNA-21) were analysed in 137 patients with HCC and liver cirrhosis and 49 healthy subjects (used as negative controls) using real-time quantitative reverse transcription polymerase chain reaction. Alpha-fetoprotein (AFP), as a routine tumour marker, was also assessed using enzyme-linked immunosorbent assay.

RESULTS

The expression levels of miRNA-21, miRNA-335 and miRNA-200 were significantly up-regulated, whereas those of miRNA-29a were remarkably down-regulated in patients with HCC compared with those in healthy subjects. miRNA-200 had the most elevated area under the receiver operating characteristic curve (AUC) among single miRNAs used to predict HCC occurrence (AUC = 0.72). The highest discriminatory power was recorded using a panel based on the combination of four miRNAs, miRNA-200, miRNA-29a, miRNA-21 and miRNA-355, and AFP levels (AUC = 0.92). The four-miRNA panel combined with AFP levels exhibited high accuracy in predicting HCC with small tumour sizes of <2 cm (AUC = 0.90) and ≥2 cm (AUC = 0.93). The combination of the four-miRNA panel and AFP resulted in an AUC value of 0.83 for single lesions, which was lesser than that recorded for ≥2 lesions (AUC = 0.94, 0.95, respectively).

CONCLUSION

The combination of the four-miRNA panel and AFP levels can be used as a sensitive and specific biomarker for HCC.