Deep sequencing and comprehensive expression analysis identifies several molecules potentially related to human poorly differentiated hepatocellular carcinoma.

Deep sequencing and comprehensive expression analysis identifies several molecules potentially related to human poorly differentiated hepatocellular carcinoma.
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DOI:
10.1002/2211-5463.12310
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发表时间:
2017-11
期刊:
影响因子:
2.6
通讯作者:
Gao Z
Gao Z
中科院分区:
生物学4区
文献类型:
--
作者:
Shao P;Sun D;Wang L;Fan R;Gao Z

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组织学分级为低分化的肝细胞癌(HCC)具有高复发、转移和不良预后。我们试图确定HCC肿瘤发生的调控机制,并确定与低分化HCC密切相关的分子。高通量测序用于构建低分化HCC组织和邻近组织的microRNA(miRNA)和mRNA表达谱。进行网络分析以研究miRNA-靶标相互作用。将HCC的miRNA和mRNA数据与来自癌症基因组图谱(TCGA)门户的四种肿瘤等级相结合,能够识别潜在的密切相关分子,用于低分化HCC的早期诊断。还进行了RNA-seq数据的电子验证和生存分析。在HCC肿瘤和配对的非肿瘤组织之间总共鉴定了1051个差异表达的基因和165个差异表达的miRNA。基于3718个miRNA-靶标相互作用,我们建立了一个miRNA-靶标相互作用网络,靶基因主要参与胆汁酸的生物合成和胆汁分泌。整合TCGA中HCC的表达数据表明,TM 4SF 1和ANXA 2两种蛋白是低分化HCC的初步诊断的令人信服的指标。生存分析结果显示,ANXA 2、C8 orf 33和IGF 2BP 3蛋白与肝癌患者的生存时间相关。此外,我们认为hsa-miR-1180可能是低分化HCC的有效生物标志物。三种分子,TM 4SF 1,ANXA 2和C8 orf 33,是区分低分化和高分化HCC的潜在生物标志物。
Hepatocellular carcinoma (HCC) that is graded histologically as poorly differentiated has a high recurrence, metastasis and poor prognosis. We sought to determine the regulatory mechanisms of HCC tumorigenesis and to identify molecules closely related to poorly differentiated HCC. High‐throughput sequencing was used to construct microRNA (miRNA) and mRNA expression profiles for poorly differentiated HCC tissues and adjacent tissues. Network analysis was carried out to study miRNA–target interactions. Integrating the miRNA and mRNA data of HCC with four tumor grades from The Cancer Genome Atlas (TCGA) portal enabled the identification of potential closely related molecules for early diagnosis of poorly differentiated HCC. Electronic validation of RNA‐seq data and survival analysis was also performed. In total, 1051 differentially expressed genes and 165 differentially expressed miRNAs were identified between HCC tumor and paired non‐tumorous tissue. Based on 3718 miRNA–target interactions, we established an miRNA–target interaction network; the target genes were mainly involved in bile acid biosynthesis and bile secretion. Integrating expression data of HCC from TCGA indicated that two proteins, TM4SF1 and ANXA2, are convincing indicators for initial diagnosis of poorly differentiated HCC. According to the survival analysis, three proteins, ANXA2, C8orf33 and IGF2BP3, were identified as being associated with the survival time of HCC patients. Moreover, we suggest that hsa‐miR‐1180 may be an effective biomarker for poorly differentiated HCC. Three molecules, TM4SF1, ANXA2 and C8orf33, are potential biomarkers for distinguishing poorly differentiated from well‐differentiated HCC.
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