肝细胞癌中ITGB超家族成员的预后价值和潜在分子机制。
Prognostic value and potential molecular mechanism of ITGB superfamily members in hepatocellular carcinoma.
发表日期:2023 Aug 18
作者:
Haixiang Xie, Chongjiu Qin, Xin Zhou, Junqi Liu, Kejian Yang, Jusen Nong, Jianzhu Luo, Tao Peng
来源:
GENES & DEVELOPMENT
摘要:
我们使用The Cancer Genome Atlas (TCGA), cBioPortal, Gene Expression Profiling Interactive Analysis (GEPIA), 人体蛋白图谱(Human Protein Atlas, HPA), Search Tool for the Retrieval of Interacting Genes/Proteins, GeneMANIA, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), TIMER和Gene set enrichment analysis (GSEA)等数据库,研究了整合素β(ITGB)超家族在肝细胞癌(HCC)中的预后价值和潜在分子机制。ITGB4/5 mRNA 在HCC组织中上调,而在正常肝组织中下调,而ITGB2/3/8的水平在HCC组织中较低。在HCC中,ITGB4是最常见的突变ITGB基因。接收操作特征曲线(ROC)分析显示,ITGB2/3/4/5/7/8的表达水平在区分HCC组织和健康肝组织方面具有显著的诊断价值,其中ITGB8的诊断效能最高。与健康肝组织相比,ITGB1/3/6/8在HCC组织中也上调表达。我们通过免疫组化(IHC)验证了ITGB8的表达。此外,ITGB6和ITGB7的表达水平与HCC患者的总生存率(OS)密切相关。ITGB超家族成员在蛋白质结构中显示相似性和相互作用。此外, ITGB6和ITGB7与多种免疫细胞浸润呈负相关。GSEA结果显示,ITGB6在HCC迁移和复发中富集,而ITGB7在HIPPO,TOLL和JAK-STAT信号通路中显著富集。总之,ITGB6和ITGB7基因可能是HCC的预后生物标志物(prognostic biomarkers)。版权所有 © 2023 作者. Wolters Kluwer 健康公司出版。
We analyzed the prognostic value and potential molecular mechanisms of the members of integrin β (ITGB)superfamily in hepatocellular carcinoma (HCC) using data from The Cancer Genome Atlas (TCGA), cBioPortal, Gene Expression Profiling Interactive Analysis (GEPIA), Human Protein Atlas (HPA) HPA, Search Tool for the Retrieval of Interacting Genes/Proteins, GeneMANIA, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), TIMER and Gene set enrichment analysis (GSEA) databases. ITGB4/5 mRNA was upregulated in HCC tissues in contrast to the normal liver tissues, whereas ITGB2/3/8 levels were lower in the former. ITGB4 was the most frequently mutated ITGB gene in HCC. Receiver operating characteristic curve (ROC) analysis showed that the expression levels of ITGB2/3/4/5/7/8 had significant diagnostic value in distinguishing HCC tissues from healthy liver tissues, ITGB8 had the highest diagnostic efficacy. The ITGB1/3/6/8 were also upregulated in the HCC tissues in contrast to healthy liver tissues. The expression of ITGB8 was verified by immunohistochemistry (IHC). Furthermore, ITGB6 and ITGB7 expression levels were strongly associated with the overall survival (OS) of HCC patients. The ITGB superfamily members exhibited homology and interactions in protein structure. In addition, ITGB6 together with ITGB7 were negatively related to the infiltration of multiple immune cell populations. GSEA results showed that ITGB6 was enriched in HCC migration and recurrence, whereas ITGB7 was significantly enriched in HIPPO, TOLL and JAK-STAT signaling pathways. In conclusion, ITGB6 and ITGB7 genes are possible to be prognostic biomarkers for HCC.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.