Highly Sensitive Circulating MicroRNA Panel for Accurate Detection of Hepatocellular Carcinoma in Patients With Liver Disease

Abstract

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer deaths worldwide. The high mortality rate in HCC is largely due to the difficulty of early detection. In this study, to improve patient outcomes, serum samples from 345 patients with HCC, 46 patients with chronic hepatitis (CH), 93 patients with liver cirrhosis (LC), and 1,033 healthy individuals were analyzed with microRNA (miRNA) microarrays. We investigated the diagnostic potential of circulating miRNAs in serum and developed a detection model of HCC, including early stage. A diagnostic model was constructed based on the expression levels of a combination of miRNAs in a discovery set. We selected 52 miRNAs that had altered expressions according to disease progression status, established the diagnostic model with a combination of eight miRNAs in the discovery set, and tested the model in a validation set. The diagnostic values for discriminating cancer from HCC at-risk control samples were as follows: area under the curve, 0.99; sensitivity, 97.7%; specificity, 94.7%. With this model, 98% of stage I HCC cases were detected; these results were much better than those observed from conventional methods. Conclusion: Circulating miRNAs could serve as biomarkers for the accurate detection of HCC. Because the diagnostic accuracy was maintained even in stage I, this may represent an accurate detection method even for early stage HCC. (Hepatology Communications 2020;4:284-297).

Serum Biomarkers for the Prediction of Hepatocellular Carcinoma

“…The miRNA panel detected 8 cases of HCC at 12 months before diagnosis (8 out of 27), whereas AFP could detect only 2 cases. A recent study evaluated the use of circulating miRNAs to identify HCC by analyzing serum samples from 353 HCC patients, 46 chronic hepatitis patients, and 93 patients with liver cirrhosis [ 38 ]. This study found that a combination of 8 miRNAs, miR-320b, miR-663a, miR-4448, miR-4651, miR-4749–5p, miR-6724–5p, miR-6877–5p, and miR-6885–5p could discriminate HCC from at-risk control samples (chronic hepatitis and/or cirrhosis) with a diagnostic value AUC of 0.99, a sensitivity of 97.7% and specificity of 94.7%.…”

Liquid Biopsies in Hepatocellular Carcinoma: Are We Winning?

“…Other examples of combined miRNA panels include serum levels of miR-375, miR-10a, miR-122, and miR-423, found elevated in patients with HCC comparing with healthy controls (AUROC of 0.995) [140]; miR-101-3p, miR-1246, and miR-106b-3p, which exhibited high diagnostic accuracy for HCC when patients with cirrhosis (AUC of 0.99) were compared with control subjects (AUC of 1.00) [141]; or miR-122, miR-142-3p and miR-486 in distinguishing HCC from cirrhosis in patients with chronic Hepatitis C (AUC = 0.94) [142]. Interestingly, a recent study combining eight miRNAs showed a sensitivity of 97.7% and a specificity of 94.7% in discriminating the presence of HCC in high risk patients, allowing the detection of 98% stage I HCC cases [143].…”

Reversal of doxorubicin resistance in lung cancer cells by neferine is explained by nuclear factor erythroid-derived 2-like 2 mediated lung resistance protein down regulation

“…However, since this result may be specific to ethnic groups, an analysis that integrates multiracial data will be required in the future. Recently, Yamamoto et al [91] reported that an eight-miRNA panel (miR-320b, miR-663a, miR-4448, miR-4651, miR-4749-5p, miR-6724-5p, miR-6877-5p, and miR-6885-5p) could accurately distinguish HCC patients from healthy (AUC = 1.00; sensitivity, 97.7%; and specificity, 98.4%) and chronic hepatitis/cirrhosis patients (AUC = 0.99; sensitivity, 97.7%; and specificity, 94.7%) in a study of 344 HCC patients. Importantly, compared with serum AFP, the eight-miRNA panel showed high sensibility (stage I, 98%) at the early stage of HCC.…”