全基因组长链非编码 RNA 和信使 RNA 表达谱显示，暴露于无机元素与肝细胞癌发展风险之间存在关联。
Genome-wide long noncoding RNA and mRNA expression profiles demonstrate associations between exposure to inorganic elements and the risk of developing hepatocellular carcinoma.
机构信息
Center of Clinical Laboratory, Zhongshan Hospital, School of Medicine, Xiamen University, 209 Hubin South Road, Xiamen, 361004, Fujian Province, China.
Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Xiamen, China.
出版信息
BMC Med Genomics. 2021 Mar 18;14(1):85. doi: 10.1186/s12920-021-00927-w.
BACKGROUND
Long noncoding RNAs (lncRNAs) are closely associated with the development of hepatocellular carcinoma (HCC). The present study conducted a genome-wide microarray analysis and qPCR validation to obtain comprehensive insights into this issue.
METHODS
Thirty male HCC patients with chronic HBV infection were included in the present study. Primary HCC tissue and normal tissue were collected. Double-stranded complementary DNA synthesized from 10 pairs of samples was labeled and hybridized to a microarray chip. Further analyses, such as hierarchical clustering, gene ontology (GO) and pathway analyses, were performed. In addition, qPCR validation was performed on tissue samples and additional serum samples.
RESULTS
The microarray analysis identified 946 upregulated and 571 downregulated lncRNAs and 1720 upregulated and 1106 downregulated mRNAs. Among these RNAs, ENST00000583827.1 (fold change: 21) and uc010isf.1 (fold change: 18) were the most over- and underexpressed lncRNAs in the HCC tissues, respectively. For the mRNAs, KIF20A (fold change: 26) and HEPACAM (fold change: 50) were the most over- and underexpressed in the HCC tissues, respectively. The GO analysis demonstrated that the most differentially expressed mRNAs were related to the response of metal ions. The pathway analysis also suggested that the most enriched pathway was mineral absorption.
CONCLUSIONS
The subsequent qPCR validation exhibited high consistency with the microarray analysis, except for three lncRNAs. The qPCR analysis also demonstrated that TCONS_00008984 had a 767-fold overexpression level in HCC tissues when compared with normal tissues, and this finding was confirmed in the serum samples; therefore, TCONS_00008984 has the potential to serve as a diagnostic marker or prognostic indicator. The GO and pathway analyses indicated that exposure to inorganic elements may be involved in HCC risk.
背景
长链非编码 RNA（lncRNA）与肝细胞癌（HCC）的发生发展密切相关。本研究通过全基因组微阵列分析和 qPCR 验证，全面探讨了这一问题。
方法
本研究纳入 30 例慢性 HBV 感染的男性 HCC 患者，采集其 HCC 组织和正常组织，将 10 对样本的双链互补 DNA 合成并标记后与微阵列芯片杂交，进行聚类分析、基因本体（GO）和通路分析等。此外，对组织样本和另外的血清样本进行 qPCR 验证。
结果
微阵列分析鉴定出 946 个上调和 571 个下调的 lncRNA，以及 1720 个上调和 1106 个下调的 mRNA。在这些 RNA 中，ENST00000583827.1（倍数变化：21）和 uc010isf.1（倍数变化：18）分别是 HCC 组织中表达上调和下调最显著的 lncRNA。对于 mRNA，KIF20A（倍数变化：26）和 HEPACAM（倍数变化：50）分别是 HCC 组织中表达上调和下调最显著的。GO 分析表明，差异表达最显著的 mRNAs 与金属离子的反应有关。通路分析还表明，最富集的通路是矿物质吸收。
结论
qPCR 验证结果与微阵列分析高度一致，除了 3 个 lncRNA 外。qPCR 分析还表明，与正常组织相比，TCONS_00008984 在 HCC 组织中的表达水平上调了 767 倍，在血清样本中也得到了验证；因此，TCONS_00008984 有可能成为诊断标志物或预后标志物。GO 和通路分析表明，无机元素的暴露可能与 HCC 风险有关。
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