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

Abstract

BackgroundThe 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.MethodsA 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.ResultsRAB22A 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.ConclusionsRAB22A is a potential therapeutic target for improving HCC prognosis and is closely related to immune cell infiltration.

Crucial roles of Rab22a in endosomal cargo recycling

“…In recent years, much progress has been made in understanding the pathogenic properties of Rab22a. For instance, many studies have confirmed that Rab22a is upregulated in and closely linked to the progression of various malignant tumors, especially in the HCC 5,136–138 . However, in the inverse of its pro‐oncogenic role, Rab22a‐induced extracellular vesicle (R‐EV) released from the exocytosis of Rab22a‐mediated noncanonical autophagosome fused with EE (Rafeesome) is a novel EV type that induces antitumor immunity 34 .…”

“…For instance, many studies have confirmed that Rab22a is upregulated in and closely linked to the progression of various malignant tumors, especially in the HCC. 5,[136][137][138] However, in the inverse of its pro-oncogenic role, Rab22a-induced extracellular vesicle (R-EV) released from the exocytosis of Rab22amediated noncanonical autophagosome fused with EE (Rafeesome) is a novel EV type that induces antitumor immunity. 34 We summarize recent research on the basic information of Rab22a and the BLOC-1-Rab22a-BLOC-2-KIF13A-AnxA2 complex-induced recycling tubule biogenesis as well as and the role Rab22a in cargo-specific recycling in this review.…”

AP4M1 as a prognostic biomarker associated with cell proliferation, migration and immune regulation in hepatocellular carcinoma

“…In this study, we carried out the normality test for the numerical type of variables and used the expression median to categorize the groups. When the data meet the normal distribution, we will calculate the mean ± standard deviation (SD) with the Z-score transform of the corresponding variables; If it does not conform to the normal distribution, the median of the related variables (upper quartile and lower quartile) will be calculated [ 17 , 18 ].…”

RAB22A as a predictor of exosome secretion in the progression and relapse of multiple myeloma

“…RAB22A is a member of RAS oncogene family, and its expression is increased in many cancers such as breast cancer [ 10 ], colorectal cancer [ 11 ], osteosarcoma [ 12 ] and liver cancer [ 13 ], and it is involved in the proliferation, migration and immune regulation of malignant tumors. As a small GTPase, RAB22A belongs to RAB5 subfamily, mainly located in early endosomes, Golgi bodies and late endosomes [ 14 ].…”

“…RAB22A controlled MHC-I intrinsic distribution, recycling and trafficking to dendritic cell (DC) phage, which played an extremely important role in the antigen cross-presentation reaction of DC [ 19 ]. In another study, RAB22A was significantly up-regulated in hepatocellular carcinoma, which was significantly related to the infiltration of various immune cells and the gene expression of immune checkpoints, and may lead to poor prognosis of hepatocellular carcinoma by regulating immune function [ 13 ]. However, RAB22A is rarely studied in hematological tumors, and there is no related research in MM at present.…”