Oura Kyoko, Fujita Koji, Morishita Asahiro, Iwama Hisakazu, Nakahara Mai, Tadokoro Tomoko, Sakamoto Teppei, Nomura Takako, Yoneyama Hirohito, Mimura Shima, Tani Joji, Kobara Hideki, Okano Keiichi, Suzuki Yasuyuki, Masaki Tsutomu
Department of Gastroenterology and Neurology, Kagawa University, Miki 761-0793, Japan.
Life Science Research Center, Kagawa University, Miki 761-0793, Japan.
Oncol Lett. 2019 Jul;18(1):882-890. doi: 10.3892/ol.2019.10385. Epub 2019 May 21.
During diagnosis of early stage hepatocellular carcinoma (HCC), single or small lesions are difficult to identify using screening ultrasonography, and conventional tumor markers are frequently negative. MicroRNAs (miRNAs) are small non-coding RNAs that suppress the translation of target mRNAs and exert significance as biomarkers. The aim of the present study was to use samples of patients with HCC and those with other liver diseases caused by hepatitis C virus (HCV) infection to investigate the expression profile of serum miRNAs, and identify a miRNA that can serve as a HCC biomarker. Initially, changes in 2,555 miRNAs between pre- and post-curative treatment serum from 12 patients with early stage HCC were examined using microarray analysis. The serum levels of miR-125a-5p in 40 individuals with HCV-associated chronic hepatitis (CH), liver cirrhosis (LC) or HCC were measured using reverse transcription-quantitative polymerase chain reaction, and 5 miRNAs, including miR-125a-5p, miR-423-5p, miR-1247, miR-1304 and miR-3648, were identified to be downregulated following curative treatment in patients with HCC. Among these, miR-125a-5p was identified to be similarly decreased following treatment in all patients. Additionally, the expression levels of miR-125a-5p were significantly upregulated in patients with HCC in the early and advanced stages of disease, compared with patients with CH or LC (P<0.05). Serum miR-125a-5p fluctuates depending on the presence of HCC, and may serve as a noninvasive biomarker to aid in diagnosing early carcinogenesis in HCV-associated chronic liver diseases.
在早期肝细胞癌(HCC)的诊断过程中,使用筛查超声难以识别单个或小病灶,并且传统肿瘤标志物常常呈阴性。微小RNA(miRNA)是一类小的非编码RNA,可抑制靶mRNA的翻译,并作为生物标志物发挥重要作用。本研究的目的是利用HCC患者以及由丙型肝炎病毒(HCV)感染引起的其他肝病患者的样本,研究血清miRNA的表达谱,并鉴定一种可作为HCC生物标志物的miRNA。首先,使用微阵列分析检查了12例早期HCC患者治疗前和治疗后血清中2555种miRNA的变化。使用逆转录-定量聚合酶链反应测量了40例HCV相关慢性肝炎(CH)、肝硬化(LC)或HCC患者血清中miR-125a-5p的水平,并且鉴定出包括miR-125a-5p、miR-423-5p、miR-1247、miR-1304和miR-3648在内的5种miRNA在HCC患者进行治愈性治疗后表达下调。其中,在所有患者中均鉴定出miR-125a-5p在治疗后同样降低。此外,与CH或LC患者相比,处于疾病早期和晚期的HCC患者中miR-125a-5p的表达水平显著上调(P<0.05)。血清miR-125a-5p会根据HCC的存在情况而波动,并且可能作为一种非侵入性生物标志物,有助于诊断HCV相关慢性肝病中的早期癌变。