RAB22A 在肝细胞癌中的预后价值和免疫作用特征。
Characterization of prognostic value and immunological roles of RAB22A in hepatocellular carcinoma.
机构信息
Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
出版信息
Front Immunol. 2023 Mar 3;14:1086342. doi: 10.3389/fimmu.2023.1086342. eCollection 2023.
BACKGROUND
The protein-coding gene , 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 and survival prognosis in HCC and explore the biological significance of RAB22A.
METHODS
A database-based pan-cancer expression analysis of RAB22A was performed. Kaplan-Meier analysis and Cox regression were performed to evaluate the association between 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.
RESULTS
was upregulated in HCC samples and cell lines. A high 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 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. was correlated with N6-methyladenosine expression in HCC and established -related ceRNA regulatory networks. Finally, 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, expression showed a strong correlation with various immunomarkergroups in HCC.
CONCLUSIONS
RAB22A is a potential therapeutic target for improving HCC prognosis and is closely related to immune cell infiltration.
背景
RAS 癌基因家族成员 编码的蛋白质基因在某些癌症中扩增或过表达。然而，其在肝细胞癌 (HCC) 中的作用机制尚不清楚。在这里，我们旨在研究 与 HCC 患者生存预后之间的关系，并探讨 RAB22A 的生物学意义。
方法
基于数据库的 RAB22A 泛癌症表达分析。通过 Kaplan-Meier 分析和 Cox 回归分析评估 在 HCC 中的表达与生存预后之间的关系。利用基因本体论（GO）、京都基因与基因组百科全书（KEGG）和基因集富集分析（GSEA），发现 RAB22A 在 HCC 中的各种潜在生物学功能和调控途径。使用单样本基因集富集分析（ssGSEA）方法研究肿瘤免疫浸润。在 TCGA 队列中验证 N6-甲基腺苷修饰和竞争内源性 RNA（ceRNA）的调控网络。
结果
在 HCC 样本和细胞系中上调。HCC 中高表达与性别、种族、年龄、体重、TNM 分期、病理分期、肿瘤状态、组织学分级、TP53 突变状态和甲胎蛋白 (AFP) 水平密切相关。 的过表达与总生存期（OS）、疾病特异性生存期（DSS）和无进展生存期（PFI）相关的不良预后有关。GO 和 KEGG 分析表明，与 RAB22A 相关的差异表达基因可能参与蛋白酶体蛋白分解代谢过程、ncRNA 加工、核糖体核糖体亚基、蛋白丝氨酸/苏氨酸激酶活性、蛋白丝氨酸激酶活性、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参与 T 细胞受体、共翻译蛋白、膜结合、轴突导向、核糖体、吞噬作用和真核翻译起始。在 HCC 中， 与 N6-甲基腺苷表达相关，并建立了与 相关的 ceRNA 调控网络。最后， 的表达与辅助性 T 细胞、TCM 细胞和 Th2 细胞的浸润水平呈正相关，而与细胞毒性细胞、DCs 和 pDCs 细胞呈负相关。此外， 的表达与 HCC 中的各种免疫标志物组均呈强相关性。
结论
RAB22A 是改善 HCC 预后的潜在治疗靶点，与免疫细胞浸润密切相关。
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