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. 2022 Nov 6;11(21):3517.
doi: 10.3390/cells11213517.

Bioinformatics Analysis and Validation of the Role of Lnc-RAB11B-AS1 in the Development and Prognosis of Hepatocellular Carcinoma

Dedong Wang  1   2   3 , Xiangzhi Hu  3 , Jinbin Chen  4 , Boheng Liang  1   2 , Lin Zhang  1   2 , Pengzhe Qin  1   2 , Di Wu  1   2
Affiliations

Bioinformatics Analysis and Validation of the Role of Lnc-RAB11B-AS1 in the Development and Prognosis of Hepatocellular Carcinoma

Dedong Wang et al. Cells. .

Abstract

Lnc-RAB11B-AS1 is reported to be dysregulated in several types of cancers and can function as both an oncogene and tumor suppressor gene. To evaluate the potential role of lnc-RAB11B-AS1 in hepatocellular carcinoma (HCC), we investigated and evaluated its expression in HCC based on the data mining of a series of public databases, including TCGA, GEO, ICGC, HPA, DAVID, cBioPortal, GeneMIANA, TIMER, and ENCORI. The data showed downregulation of lnc-RAB11B-AS1 in HCC and was accompanied by the synchronous downregulation of the targeted RAB11B mRNA and its protein. Low expression of lnc-RAB11B-AS1 was associated with shorter overall survival (OS) and disease-free survival (DFS) of HCC patients, PD1/PD-L1 was correlated with low expression of RAB11B. Furthermore, Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed a correlation between immune cell change and non-alcoholic fatty liver disease. The above findings revealed that lnc-RAB11B-AS1 was down-regulated in HCC and closely associated with the clinical stage of the HCC patients, suggesting that lnc-RAB11B-AS1 could be a possible predictor for HCC and a potential new therapeutic target for the treatment of HCC.

Keywords: RAB11B; hepatocellular carcinoma (HCC); lnc-RAB11B-AS1; prognosis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Comparison of lnc-RAB11B-AS1 and RAB11B expression in HCC and normal liver tissues (A–C) The expression of lnc-RAB11B-AS1 in HCC tissues and normal tissues based on TCGA-LIHC, GSE144269, GSE84402. (D–F) RAB11B expression in HCC tissues and normal tissues based on TCGA-LIHC, GSE144269, GSE84402. (G–I) The correlation analysis between lnc-RAB11B-AS1 and RAB11B in three different datasets.
Figure 2
Figure 2
Relationship between lnc-RAB11B-AS1 and RAB11B expression and the prognosis of HCC patients (A,B) The different expression status of lnc-RAB11B-AS1 in the histologic grade and clinical stage of HCC. (C,D) The change of RAB11B expression in the histologic grade and clinical stage of HCC. (E,F) The association between lnc-RAB11B-AS1 and RAB11B expression and OS in TCGA database. (G,H) The correlation between the expression of lnc-RAB11B-AS1 and RAB11B and OS in GSE144269 dataset. (I) The relationships between RAB11B expression and OS, RFS, PFS, and DSS of HCC patients in Kaplan-Meier Plotter database.
Figure 3
Figure 3
Immunohistochemical analysis of RAB11B protein in HCC tissues and adjacent noncancerous tissues. (A) Expression of RAB11B protein in two representative pairs of HCC tissues (T) and adjacent non-cancerous tissues (ANT), with magnification ×100. (B) The score histogram of RAB11B expression at protein level in HCC and non-cancerous tissues. (C,D) The relationship between RAB11B expression, OS, and DFS in HCC patients. (E) Protein network diagram of interaction with RAB11B protein. (F) Single-cell UMAP dimensionality reduction map of the liver. (G) RNA levels of RAB11B and mark genes in different single cell type clusters of the liver (Human Protein Atlas).
Figure 4
Figure 4
The signaling pathways and biological processes of lnc-RAB11B-AS1 (A) GO analysis. (B) Pathway enrichment analysis based on KEGG. (C) KEGG pathway: NAFAD. (D) Volcano plot of DEGs. Blue and red dots represent the significantly down-regulated and up-regulated DEGs, respectively. (E) Ten significantly enriched pathways based on GSEA.
Figure 5
Figure 5
Copy number variations (CNVs) of RAB11B in HCC tissues (A,B) Correlation analysis between lnc-RAB11B-AS1, RAB11B, and six immune cells in TIMER. (C) The relationship between the expression levels of two genes and 64 immune cells using xCell. (D) OncoPrint plot of lnc-RAB11B-AS1 and RAB11B alterations. (E) Genetic alteration in RAB11B might be associated with shorter OS of HCC patients. (F) Relationship between the gene mutation level of RAB11B and tumor histological grade. (G) Methylation levels of the promoter region of lnc-RAB11B-AS1 were higher in the tumor group compared to the paired normal group. (H,I) Methylation levels in different clinical stages and T stage. * p < 0.05, ** p < 0.01, *** p < 0.001.
Figure 6
Figure 6
Prediction of potential candidate miRNAs and drug sensitivity analysis (A) The prediction of the subcellular localization of lnc-RAB11B-AS1. (B) The expression status of hsa-miR-4726-5p in HCC tissues and normal tissues from ICGC. (C) Kaplan-Meier overall survival was analyzed according to hsa-miR-4726-5p expression in ICGC cohort. (D) The relationship between lnc-RAB11B-AS1 and hsa-miR-4726-5p expression in ENCORI database. (E) Correlation analysis of the expression of RAB11B and hsa-miR-4726-5p in 232 pairs of HCC tissues. (F) Relationship between lnc-RAB11B-AS1 and chemosensitivity to nine drugs.
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