Li Chengyun, Zhang Wenwen, Yang Hanteng, Xiang Jilian, Wang Xinghua, Wang Junling
Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, Gansu province, China.
Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu province, China.
PeerJ. 2020 Mar 11;8:e8758. doi: 10.7717/peerj.8758. eCollection 2020.
Hepatocellular carcinoma (HCC) is an aggressive cancer with a poor prognosis and a high incidence. The molecular changes and novel biomarkers of HCC need to be identified to improve the diagnosis and prognosis of this disease. We investigated the current research concentrations of HCC and identified the transcriptomics-related biomarkers of HCC from The Cancer Genome Atlas (TGCA) database.
We investigated the current research concentrations of HCC using literature metrology analysis for studies conducted from 2008 to 2018. We identified long noncoding RNAs (lncRNAs) that correlated with the clinical features and survival prognoses of HCC from The Cancer Genome Atlas (TGCA) database. Differentially expressed genes (lncRNAs, miRNAs, and mRNAs) were also identified by TCGA datasets in HCC tumor tissues. A lncRNA competitive endogenous RNA (ceRNA) network was constructed from lncRNAs based on intersected lncRNAs. Survival times and the association between the expression levels of the key lncRNAs of the ceRNA network and the clinicopathological characteristics of HCC patients were analyzed using TCGA. Real-time polymerase chain reaction (qRT-PCR) was used to validate the reliability of the results in tissue samples from 20 newly-diagnosed HCC patients.
Analysis of the literature pertaining to HCC research revealed that current research is focused on lncRNA functions in tumorigenesis and tumor development. A total of 128 HCC dysregulated lncRNAs were identified; 66 were included in the co-expressed ceRNA network. We analyzed survival times and the associations between the expression of 66 key lncRNAs and the clinicopathological features of the HCC patients identified from TCGA. Twenty-six lncRNAs were associated with clinical features of HCC ( < 0.05) and six key lncRNAs were associated with survival time (log-rank test < 0.05). Six key lncRNAs were selected for the validation of their expression levels in 20 patients with newly diagnosed HCC using qRT-PCR. Consistent fold changes in the trends of up and down regulation between qRT-PCR validation and TCGA proved the reliability of our bioinformatics analysis.
We used integrative bioinformatics analysis of the TCGA datasets to improve our understanding of the regulatory mechanisms involved with the functional features of lncRNAs in HCC. The results revealed that lncRNAs are potential diagnostic and prognostic biomarkers of HCC.
肝细胞癌（HCC）是一种侵袭性癌症，预后较差且发病率高。需要确定HCC的分子变化和新型生物标志物，以改善该疾病的诊断和预后。我们调查了HCC当前的研究热点，并从癌症基因组图谱（TGCA）数据库中确定了HCC的转录组学相关生物标志物。
我们使用文献计量学分析对2008年至2018年进行的研究进行调查，以了解HCC当前的研究热点。我们从癌症基因组图谱（TGCA）数据库中确定了与HCC的临床特征和生存预后相关的长链非编码RNA（lncRNA）。还通过TCGA数据集中的HCC肿瘤组织鉴定了差异表达基因（lncRNA、miRNA和mRNA）。基于相交的lncRNA构建了lncRNA竞争性内源RNA（ceRNA）网络。使用TCGA分析ceRNA网络关键lncRNA的生存时间及其表达水平与HCC患者临床病理特征之间的关联。使用实时聚合酶链反应（qRT-PCR）验证20例新诊断HCC患者组织样本结果的可靠性。
对HCC研究文献的分析表明，当前研究集中在lncRNA在肿瘤发生和肿瘤发展中的功能。共鉴定出128个HCC失调lncRNA；66个被纳入共表达ceRNA网络。我们分析了66个关键lncRNA的生存时间及其表达与从TCGA鉴定的HCC患者临床病理特征之间的关联。26个lncRNA与HCC的临床特征相关（P<0.05），6个关键lncRNA与生存时间相关（对数秩检验P<0.05）。选择6个关键lncRNA，使用qRT-PCR验证其在20例新诊断HCC患者中的表达水平。qRT-PCR验证与TCGA之间上调和下调趋势的一致倍数变化证明了我们生物信息学分析的可靠性。
我们对TCGA数据集进行了综合生物信息学分析，以增进对HCC中lncRNA功能特征相关调控机制的理解。结果表明，lncRNA是HCC潜在的诊断和预后生物标志物。
