The role of circulating microRNAs for the diagnosis of hepatitis B virus-associated hepatocellular carcinoma with low alpha-fetoprotein level: a systematic review and meta-analysis

Abstract

Background Alpha-fetoprotein (AFP) has been widely used for many years as a serum marker for hepatocellular carcinoma (HCC). However, AFP has been recognized as having poor sensitivity. More and more studies have concluded that circulating microRNAs (miRNAs) might be a promising biomarker that could complement AFP. However, the diagnostic ability of circulating miRNAs has varied among the studies. Therefore, we performed the present meta-analysis to appraise the diagnostic performance of circulating miRNAs as a biomarker for hepatitis B virus-associated HCC (HBV-HCC) patients with low AFP levels. Methods We performed a systematic review and meta-analysis of the published literature to assess the diagnostic accuracy of circulating miRNAs in differentiating HBV-HCC patients with low AFP levels from non-HCC controls. Results Circulating miRNAs showed promising potential in the diagnosis of HBV-HCC patients with low AFP levels. In the low-AFP HBV-HCC patients, the area under the curve (AUC) was 0.88 (95% confidence interval [CI]: 0.84–0.90). The pooled sensitivity and specificity were 0.84 (95% CI: 0.78–0.88) and 0.76 (95% CI: 0.69–0.83), respectively. Conclusions The detection of circulating miRNAs provides a valuable method for the diagnosis of HBV-HCC in patients with low AFP levels.

Update on the applications and limitations of alpha-fetoprotein for hepatocellular carcinoma

“…In a metanalysis, Peng et al [ 63 ] concluded that among HBV–related HCCs with low AFP levels, circulating miRNAs could be potential valuable biomarkers. For patients with AFP levels < 400 ng/mL, miR-125b and miR-205 demonstrated a sensitivity of 90% while combination of miR-15b and miR-130b had > 90% sensitivity and specificity.…”

“…For patients with AFP < 400ng/mL, the overall sensitivity and specificity were 0.84 and 0.76 with AUC of 0.88 (95%CI: 0.84–0.90). Hence, miRNAs are attractive HCC markers to detect HBV-associated HCC with low AFP levels[ 63 ].…”

Dysregulated microRNAs as a biomarker for diagnosis and prognosis of hepatitis B virus-associated hepatocellular carcinoma

“…Different miRNAs and miRNA panels have shown good capacity for separating HBV-HCC patients with negative AFP expression from HC and CHB patients (Table 5 ), such as miR-125b[ 23 ], miR-15b + miR-130b[ 9 ] miR-21 + miR-122 + miR-192[ 22 ], and miR-125b + miR-223 + miR-27a + miR-26a[ 30 ]. A meta-analysis suggests that circulating miRNAs have a relatively high diagnostic accuracy in distinguishing HBV-HCC patients with low AFP levels from non-HCC controls[ 40 ]. Therefore, circulating miRNAs may be an ideal potential diagnostic biomarker for HBV-HCC patients with low AFP levels.…”