研究动态
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在肝细胞癌中对RAB22A的预测价值和免疫作用的表征。

Characterization of prognostic value and immunological roles of RAB22A in hepatocellular carcinoma.

发表日期:2023
作者: Fukai Wen, Fanshuai Meng, Xuewen Li, Qingyu Li, Jiaming Liu, Rui Zhang, Yunzheng Zhao, Yu Zhang, Xin Wang, Shuai Ju, Yifeng Cui, Zhaoyang Lu
来源: Frontiers in Immunology

摘要:

编码蛋白基因RAB22A属于RAS癌基因家族,在某些癌症中会被扩增或过度表达。然而,它在肝细胞癌(HCC)中的作用机制仍不清楚。本研究旨在探讨RAB22A与HCC生存预后的关系,以及RAB22A的生物学意义。我们进行了基于数据库的广泛癌症表达分析,评估RAB22A表达与HCC生存预后的关联。采用基因本体论(GO)、京都基因和基因组百科全书(KEGG)以及基因集富集分析(GSEA)等方法,发现RAB22A在HCC中的各种潜在生物学功能和调控途径。采用单样本基因集富集分析(ssGSEA)法研究肿瘤免疫浸润。通过TCGA队列验证了N6-甲基腺苷酸修饰和有竞争的内源性RNA(ceRNA)的调节网络。RAB22A在HCC样本和细胞系中升高。HCC中RAB22A高表达与性别、种族、年龄、体重、TNM分期、病理分期、肿瘤状态、组织学分级、TP53突变状态和α胎儿蛋白(AFP)水平密切相关。RAB22A过表达表示不良预后,与总生存期(OS)、疾病特异性生存期(DSS)和无进展生存期(PFI)有关。GO和KEGG分析表明,与RAB22A相关的差异表达基因可能涉及蛋白酶体蛋白降解过程、ncRNA加工、核糖体亚基、蛋白丝/苏氨酸激酶活性、蛋白丝/苏氨酸激酶活性、内吞作用和非酒精性脂肪性肝病。GSEA分析表明,与RAB22A相关的差异表达基因可能涉及T细胞受体、共翻译蛋白、结合膜、轴突导向、核糖体、吞噬作用和真核生物翻译起始等。RAB22A在HCC中与N6-甲基腺苷酸表达相关,并建立了与RAB22A相关的ceRNA调节网络。最后,RAB22A表达与T辅助细胞、Tcm细胞和Th2细胞的浸润水平呈正相关,相反地,我们观察到与细胞毒性细胞、DCs和pDCs细胞的负相关。此外,RAB22A表达与HCC中的各种免疫标记组之间存在强相关性。RAB22A是改善HCC预后的潜在治疗靶点,并与免疫细胞浸润密切相关。 ©2023 Wen, Meng, Li, Li, Liu, Zhang, Zhao, Zhang, Wang, Ju, Cui and Lu.
The protein-coding gene RAB22A, a member of the RAS oncogene family, is amplified or overexpressed in certain cancers. However, its action mechanism in hepatocellular carcinoma (HCC) remains unclear. Here, we aimed to examine the connection between RAB22A and survival prognosis in HCC and explore the biological significance of RAB22A.A database-based pan-cancer expression analysis of RAB22A was performed. Kaplan-Meier analysis and Cox regression were performed to evaluate the association between RAB22A expression and survival prognosis in HCC. Using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA), various potential biological functions and regulatory pathways of RAB22A in HCC were discovered. Tumor immune infiltration was studied using the single sample gene set enrichment analysis (ssGSEA) method. N6-methyladenosine modifications and the regulatory network of competitive endogenous RNA (ceRNA) were verified in the TCGA cohort.RAB22A was upregulated in HCC samples and cell lines. A high RAB22A expression in HCC was strongly correlated with sex, race, age, weight, TNM stage, pathological stage, tumor status, histologic grade, TP53 mutation status, and alpha fetal protein (AFP) levels. Overexpression of RAB22A indicated a poor prognosis was related to overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI). GO and KEGG analyses revealed that the differentially expressed genes related to RAB22A might be involved in the proteasomal protein catabolic process, ncRNA processing, ribosome ribosomal subunit, protein serine/threonine kinase activity, protein serine kinase activity, Endocytosis, and non-alcoholic fatty liver disease. GSEA analyses revealed that the differentially expressed genes related to RAB22A might be involved in the T cell receptor, a co-translational protein, that binds to the membrane, axon guidance, ribosome, phagocytosis, and Eukaryotic translation initiation. RAB22A was correlated with N6-methyladenosine expression in HCC and established RAB22A-related ceRNA regulatory networks. Finally,RAB22A expression was positively connected the levels of infiltrating with T helper cells, Tcm cells, and Th2 cells,In contrast, we observed negatively correlations with cytotoxic cells, DCs, and pDCs cells.Moreover,RAB22A expression showed a strong correlation with various immunomarkergroups in HCC.RAB22A is a potential therapeutic target for improving HCC prognosis and is closely related to immune cell infiltration.Copyright © 2023 Wen, Meng, Li, Li, Liu, Zhang, Zhao, Zhang, Wang, Ju, Cui and Lu.