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与肝细胞癌微血管侵犯相关的微小RNA及其对肝切除患者的预后影响

MicroRNAs associated with microvascular invasion in hepatocellular carcinoma and their prognostic impacts in patients undergoing hepatic resection.

作者信息

Song Sung Kyu, Park Min Geun, Park Seung-Keun, Chung Chul-Woon, Park Yongkeun

机构信息

Department of Surgery, Catholic Kwandong University International St. Mary's Hospital, Catholic Kwandong University College of Medicine, Incheon 22711, Republic of Korea.

Department of Supercomputing M&S Technology Development, Korea Institute of Science and Technology Information, Daejeon 34141, Republic of Korea.

出版信息

Oncol Lett. 2019 Dec;18(6):6293-6303. doi: 10.3892/ol.2019.10987. Epub 2019 Oct 14.

Abstract

Although microvascular invasion (McVI) has prognostic value for patients with hepatocellular carcinoma (HCC) who have undergone hepatic resection, few studies have investigated the relationship between McVI and the aberrant expression of microRNAs (miRNAs). The present study identified the miRNAs that were selectively expressed in HCC with McVI and investigated their prognostic value. Clinical data and the miRNA expression profiles of 372 patients with HCC were extracted from The Cancer Genome Atlas database. miRNAs that were differentially expressed between patients with McVI and those without vascular invasion (VI) were identified and investigated as potential prognostic factors for HCC. The results demonstrated that McVI was a significant predictor of shortened recurrence-free survival (RFS). The 3 year RFS rate in patients with HCC accompanied by McVI was 28.2 and 49.3% in HCC without VI (P<0.001). miRNA-141/-582/-9 were upregulated, while miRNA-675 was downregulated in patients with McVI when compared with HCC patients without VI. Log fold-changes of miRNA-141/-582/-675/-9 were 0.80 [false discovery rate (FDR), 0.005], 0.55 (FDR, 0.045), -0.99 (FDR, 0.005) and 1.22 (FDR, <0.001), respectively. Kaplan-Meier analysis indicated that the overexpression of miR-141/-582/-9 was significantly associated with poor RFS and a poor overall survival. A text mining analysis revealed that these miRNAs were significantly associated with multifaceted hallmarks of cancer, including 'invasion and metastasis'. In conclusion, the overexpression of miRNA-141/-582/-9 was associated with McVI and a poor survival in patients undergoing hepatic resection for HCC.

摘要

尽管微血管侵犯(McVI)对接受肝切除的肝细胞癌(HCC)患者具有预后价值,但很少有研究探讨McVI与微小RNA(miRNA)异常表达之间的关系。本研究鉴定了在伴有McVI的HCC中选择性表达的miRNA,并研究了它们的预后价值。从癌症基因组图谱数据库中提取了372例HCC患者的临床数据和miRNA表达谱。鉴定了在伴有McVI的患者和无血管侵犯(VI)的患者之间差异表达的miRNA,并将其作为HCC的潜在预后因素进行研究。结果表明,McVI是无复发生存期(RFS)缩短的重要预测指标。伴有McVI的HCC患者3年RFS率为28.2%,无VI的HCC患者为49.3%(P<0.001)。与无VI的HCC患者相比,伴有McVI的患者中miRNA-141/-582/-9上调,而miRNA-675下调。miRNA-141/-582/-675/-9的对数变化倍数分别为0.80[错误发现率(FDR),0.005]、0.55(FDR,0.045)、-0.99(FDR,0.005)和1.22(FDR,<0.001)。Kaplan-Meier分析表明,miR-141/-582/-9的过表达与不良的RFS和总生存期显著相关。文本挖掘分析显示,这些miRNA与癌症的多方面特征显著相关,包括“侵袭和转移”。总之,miRNA-141/-582/-9的过表达与McVI以及接受HCC肝切除患者的不良生存相关。

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