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致癌长链非编码 RNA MALAT1 与 HCV 相关的肝细胞癌。

Oncogenic long noncoding RNA MALAT1 and HCV-related hepatocellular carcinoma.

机构信息

Genetics Unit, Department of Histology and Cell Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt; Center of Excellence of Molecular and Cellular Medicine, Suez Canal University, Ismailia, Egypt.

Genetics Unit, Department of Histology and Cell Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.

出版信息

Biomed Pharmacother. 2018 Jun;102:653-669. doi: 10.1016/j.biopha.2018.03.105. Epub 2018 Apr 5.

Abstract

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide. The oncogenic function of the long non-coding RNA; metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in HCC remains unclear. We aimed to evaluate MALAT1 serum expression profile in HCC and explore its relation to the clinicopathological features. Quantitative Real Time-Polymerase Chain Reaction was applied in 70 cohorts (30 HCC, 20 HCV, 20 controls). Further meta-analysis of clinical studies and in vitro validated experiments was employed. Serum MALAT1 showed area under the curve of 0.79 and 0.70 to distinguish patients with cancer from normal and cirrhotic individuals at fold change of 1.0 and 1.26, respectively. Expression level was significantly higher in males (P <0.001) and patients with massive ascites (P = 0.005). Correlation analysis showed positive correlation of MALAT1 with total bilirubin (r = 0.456, P <0.001) and AST (r = 0.280, P = 0.019), and negative correlation with the hemoglobin level (r = 0.312, P = 0.009). Meta-analysis showed that the over-expressed MALAT1 was linked to tumor number [Cohen's d = 0.450, 95% CI (0.21 to 0.68)], clinical stage [Cohen's d = 0.048, 95% CI (-0.83 to 0.74)], and AFP level [Cohen's d = 0.354, 95% CI (0.1 to 0.57)]. In silico data analysis and systematic review confirmed MALAT1 oncogenic function in cancer development and progression. In conclusion, circulatory MALAT1 might represent a putative non-invasive prognostic biomarker indicating worse liver failure score in HCV-related HCC patients with traditional markers. Large-scale verification is warranted in future studies.

摘要

肝细胞癌(HCC)是全球癌症相关死亡的第二大主要原因。长链非编码 RNA;转移相关肺腺癌转录本 1(MALAT1)在 HCC 中的致癌功能尚不清楚。我们旨在评估 HCC 中 MALAT1 的血清表达谱,并探讨其与临床病理特征的关系。在 70 个队列(30 个 HCC、20 个 HCV、20 个对照)中应用定量实时聚合酶链反应。进一步进行了临床研究的荟萃分析和体外验证实验。血清 MALAT1 在 1.0 和 1.26 的折叠变化时,分别以 0.79 和 0.70 的曲线下面积区分癌症患者与正常人和肝硬化个体。在男性(P<0.001)和大量腹水患者(P=0.005)中表达水平显着更高。相关性分析显示 MALAT1 与总胆红素(r=0.456,P<0.001)和 AST(r=0.280,P=0.019)呈正相关,与血红蛋白水平呈负相关(r=0.312,P=0.009)。荟萃分析表明,过度表达的 MALAT1与肿瘤数量有关[Cohen's d=0.450,95%CI(0.21 至 0.68)],临床分期[Cohen's d=0.048,95%CI(-0.83 至 0.74)]和 AFP 水平[Cohen's d=0.354,95%CI(0.1 至 0.57)]。计算机数据分析和系统评价证实了 MALAT1 在癌症发展和进展中的致癌作用。总之,循环 MALAT1 可能代表一种潜在的非侵入性预后生物标志物,可指示 HCV 相关 HCC 患者传统标志物中更严重的肝衰竭评分。在未来的研究中需要进行大规模验证。

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