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.

日本語要旨:

死亡率の高い肝細胞がん（HCC）の早期発見に血清microRNAマーカーが有効であることを示した。健常者と慢性肝炎、肝硬変、HCCの患者群で血中miRNAの発現を調べ、疾患の進行に連動する52のmiRAN群を抽出した。これらを用いて慢性肝炎・肝硬変群とHCCを鑑別するマーカーセットを探索した結果、HCCステージI を高性能（感度97.7%、特異度94.7％）に識別する８個のmiRNAマーカーセットが得られた。