Six immune-related promising biomarkers may promote hepatocellular carcinoma prognosis: a bioinformatics analysis and experimental validation.
Six immune-related promising biomarkers may promote hepatocellular carcinoma prognosis: a bioinformatics analysis and experimental validation.
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DOI：
10.1186/s12935-023-02888-9
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发表时间：
2023-03-23
影响因子：
5.8
通讯作者：
Dong, Ling
中科院分区：
文献类型：
--
作者：
Lin, Xia-Hui;Li, Dong-ping;Liu, Zhi-Yong;Zhang, Si;Tang, Wen-qing;Chen, Rong-xin;Weng, Shu-qiang;Tseng, Yu-jen;Xue, Ru-yi;Dong, Ling
近年来研究发现，肝细胞癌（HCC）的发生发展与miRNA和mRNA表达异常及免疫微环境失调密切相关。特别是，免疫相关的竞争性内源性RNA（ceRNA）机制在HCC进展中起着至关重要的作用。然而，其潜在机制仍不清楚。从Immport、GEO和TCGA数据库获得差异表达的免疫相关基因。在肝癌组织和癌旁正常组织中的mRNA和蛋白表达水平得到证实，我们进一步研究这些生物标志物的甲基化水平，以探讨它们的功能。然后，使用TIMER和TISCH数据库来评估免疫浸润与枢纽基因之间的关系。采用生存分析、单变量和多变量考克斯模型评价hub基因与HCC诊断的相关性。使用qRT-PCR和免疫组织化学在6个HCC细胞系和15个HCC样品中实验验证了Hub基因表达。将中心基因上传到DSigDB用于药物预测富集分析。我们发现具有异常miRNAs（hsa-miR-125 b-5 p和hsa-miR-21- 5 p）及其靶基因（NTF 3、PSMD 14、CD 320和SORT 1）的患者预后较差。对miRNA靶基因的甲基化分析表明，甲基化水平的改变也是诱导肿瘤发生的一个因素。我们还发现由miRNA-mRNA相互作用引起的HCC进展的发展可能与免疫细胞的浸润密切相关。此外，GSEA、GO和KEGG分析表明，几种常见的免疫相关生物学过程和途径与miRNA靶向基因相关。qRT-PCR、免疫组化和蛋白质印迹的结果与我们的生物信息学结果一致，表明异常miRNAs及其靶基因可能影响HCC的进展。简而言之，我们的研究系统地描述了HCC中miRNA-mRNA相互作用的机制，并预测了与HCC进展的免疫过滤相关的有希望的生物标志物。在线版本包含补充材料，可通过10.1186/s12935-023-02888-9获得。
Abnormal miRNA and mRNA expression and dysregulated immune microenvironment have been found to frequently induce the progression of hepatocellular carcinoma (HCC) in recent reports. In particular, the immune-related competing endogenous RNAs (ceRNA) mechanism plays a crucial role in HCC progression. However, the underlying mechanisms remain unclear. Differentially expressed immune-related genes were obtained from the Immport, GEO, and TCGA databases. The mRNA and protein expression levels in HCC tissues and adjacent normal tissues were confirmed, and we further investigated the methylation levels of these biomarkers to explore their function. Then, the TIMER and TISCH databases were used to assess the relationship between immune infiltration and hub genes. Survival analysis and univariate and multivariate Cox models were used to evaluate the association between hub genes and HCC diagnosis. Hub gene expression was experimentally validated in six HCC cell lines and 15 HCC samples using qRT-PCR and immunohistochemistry. The hub genes were uploaded to DSigDB for drug prediction enrichment analysis. We identified that patients with abnormal miRNAs (hsa-miR-125b-5p and hsa-miR-21-5p) and their targeted genes (NTF3, PSMD14, CD320, and SORT1) had a worse prognosis. Methylation analysis of miRNA-targeted genes suggested that alteration of methylation levels is also a factor in the induction of tumorigenesis. We also found that the development of HCC progression caused by miRNA-mRNA interactions may be closely correlated with the infiltration of immunocytes. Moreover, the GSEA, GO, and KEGG analysis suggested that several common immune-related biological processes and pathways were related to miRNA-targeted genes. The results of qRT-PCR, immunohistochemistry, and western blotting were consistent with our bioinformatics results, suggesting that abnormal miRNAs and their targeted genes may affect HCC progression. Briefly, our study systematically describes the mechanisms of miRNA-mRNA interactions in HCC and predicts promising biomarkers that are associated with immune filtration for HCC progression. The online version contains supplementary material available at 10.1186/s12935-023-02888-9.
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影响因子：
23.9
作者：
Buckley, Shannon M.;Aranda-Orgilles, Beatriz;Strikoudis, Alexandros;Apostolou, Effie;Loizou, Evangelia;Moran-Crusio, Kelly;Farnsworth, Charles L.;Koller, Antonius A.;Dasgupta, Ramanuj;Silva, Jeffrey C.;Stadtfeld, Matthias;Hochedlinger, Konrad;Chen, Emily I.;Aifantis, Iannis
通讯作者：
Aifantis, Iannis
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影响因子：
12.4
作者：
Jing C;Duan Y;Zhou M;Yue K;Zhuo S;Li X;Liu D;Ye B;Lai Q;Li L;Yao X;Wei H;Zhang W;Wu Y;Wang X
通讯作者：
Wang X
影响因子：
3.7
作者：
Howe EN;Cochrane DR;Cittelly DM;Richer JK
通讯作者：
Richer JK
影响因子：
28.2
作者：
Karreth FA;Pandolfi PP
通讯作者：
Pandolfi PP
影响因子：
5.7
作者：
Gallery, Melissa;Blank, Jonathan L.;MacBeth, Kyle J.
通讯作者：
MacBeth, Kyle J.