Identification of 9-Core Immune-Related Genes in Bladder Urothelial Carcinoma Prognosis

Lei, Na; Bai, Yu; Sun, Yu; Wang, Zhuo; Wang, Wei; Lin, Yuan; Zhao, Chenghai

doi:10.3389/fonc.2020.01142

Cited by 21 publications

(22 citation statements)

References 32 publications

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“…but its expression and function in BC are still unclear. Recently, some studies have used databases to analyze the prognostic relevance of Rac3 in BC [23][24][25][26][27], but strict inclusion criteria were in place for the patients with BC in this study, and the number of patients we analyzed was different. We first performed Kaplan-Meier survival analysis, followed by univariate and multivariate Cox analysis.…”

Section: Discussionmentioning

confidence: 99%

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Rac3 Expression and its Clinicopathological Significance in Patients With Bladder Cancer

Chen¹,

Nie²,

Cao³

et al. 2021

Pathol. Oncol. Res.

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Background: Ras-related C3 botulinum toxin substrate 3 (Rac3) is overexpressed in malignancies and promotes tumor progression. However, the correlations between Rac3 expression and the clinicopathological characteristics and prognoses of patients with bladder cancer (BC) remain unclear.Methods: Data from The Cancer Genome Atlas (TCGA) were used to analyze Rac3 expression in BC and normal bladder tissues and validated using the Oncomine database, quantitative real-time PCR (qRT-PCR) and western blot. The Kaplan-Meier method was used to analyze the relationship between Rac3 expression and the prognosis of patients with BC. Cox univariate and multivariate analyses of BC patients overall survival (OS) were performed. Signaling pathways that potentially mediate Rac3 activity in BC were then analyzed by gene set enrichment analysis (GSEA).Results: The Rac3 expression in BC tissues was significantly higher than that in normal bladder tissues. Rac3 expression was significantly correlated with grade and stage. Overexpression of Rac3 was associated with a poor prognosis. GSEA showed that the cell cycle, DNA replication, p53 signaling pathway and mismatch repair were differentially enriched in the high Rac3 expression phenotype. The qRT-PCR and western blot results confirmed that the Rac3 expression in BC tissues was higher than that in normal bladder tissues.Conclusion: Rac3 is highly expressed in BC, which is related to the advanced clinicopathological variables and adverse prognosis of patients with BC. These results provide a new therapeutic target for BC.

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Section: Discussionmentioning

confidence: 99%

“…We first performed Kaplan-Meier survival analysis, followed by univariate and multivariate Cox analysis. Qiu et al [23] and Liu et al [24] screened only prognostic immune-related genes with univariate Cox analysis, while Na et al [25] and Tang et al…”

Section: Discussionmentioning

confidence: 99%

Rac3 Expression and its Clinicopathological Significance in Patients With Bladder Cancer

Chen¹,

Nie²,

Cao³

et al. 2021

Pathol. Oncol. Res.

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“…SH3 domain-binding protein 2 (SH3BP2) is a pathogenic gene of Cherubism and some studies have suggested that its protein was helpful to regulate the signaling pathway of B cells and macrophages in the immune system. However, its role in cancer is still unclear, several studies have found that SH3BP2 was a protective factor ( 57 – 59 ) and may be a tumor suppressor gene in bladder cancer ( 60 ). In our study, these two genes were also found to be protective factors, which is consistent with previous studies.…”

Section: Discussionmentioning

confidence: 99%

Identification of Tumor Microenvironment-Related Alternative Splicing Events to Predict the Prognosis of Endometrial Cancer

Liu

et al. 2021

Front. Oncol.

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BackgroundEndometrial cancer (EC) is one of the most common female malignant tumors. The immunity is believed to be associated with EC patients’ survival, and growing studies have shown that aberrant alternative splicing (AS) might contribute to the progression of cancers.MethodsWe downloaded the clinical information and mRNA expression profiles of 542 tumor tissues and 23 normal tissues from The Cancer Genome Atlas (TCGA) database. ESTIMATE algorithm was carried out on each EC sample, and the OS-related different expressed AS (DEAS) events were identified by comparing the high and low stromal/immune scores groups. Next, we constructed a risk score model to predict the prognosis of EC patients. Finally, we used unsupervised cluster analysis to compare the relationship between prognosis and tumor immune microenvironment.ResultsThe prognostic risk score model was constructed based on 16 OS-related DEAS events finally identified, and then we found that compared with high-risk group the OS in the low-risk group was notably better. Furthermore, according to the results of unsupervised cluster analysis, we found that the better the prognosis, the higher the patient’s ESTIMATE score and the higher the infiltration of immune cells.ConclusionsWe used bioinformatics to construct a gene signature to predict the prognosis of patients with EC. The gene signature was combined with tumor microenvironment (TME) and AS events, which allowed a deeper understanding of the immune status of EC patients, and also provided new insights for clinical patients with EC.

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“…MMP9 mRNA expression was higher in invasive UC than that in super cial UC [46]. Besides, Lei et al [8] revealed MMP9 could promote cancer invasion, metastasis and angiogenesis, while its expression was correlated with UC grade, invasiveness and poor prognosis. Wu et al [47] found that the Wnt signaling pathway would regulate UC metastasis through activating MMP9, and showed that MMP9 may be regulated by miR-3713 in UC cells.…”

Section: Discussionmentioning

confidence: 99%

“…Nowadays, more studies focus on the roles of immune checkpoint inhibitors (ICIs) and immunocytes in pathogenesis, immunotherapy of cancer, as well as disease progression [7]. Interaction between tumor cells and immunocytes suppressed immune response and promoted tumor progression [8][9][10]. In 1976, Bacillus Calmette-Guerin was rst used as an immune agent for treating UC [11] as it showed anti-tumor effects by activating the immune system and inducing in ammatory reaction [12].…”

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confidence: 99%

Identification of Prognostic Biomarkers of Potential Hub Genes in Urothelial Carcinoma and Function in Microenvironment

Chu

Zhang

Gong

et al. 2021

Preprint

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Background Urothelial carcinoma (UC) is the most common histological type of urinary system. In the past decades, despite the advances in UC diagnosis and therapy, there are still challenges to improve the overall survival (OS) of UC patients. PD-L1 inhibitor and PD-1 inhibitor have been approved for treating invasive UC, however, only about 20% of patients with metastatic UC show clinical benefits from immune checkpoint inhibitors. Therefor, bioinformatics tools were utilized to screen prognostic-related biomarkers, and analyze their relationship with immunocyte in UC, hoping to provide new ideas for the clinical treatment of UC patients.Methods Three gene expression profiles (i.e. GSE32548, GSE32894 and GSE48075) were selected from GEO, and divide them into invasive and superficial UC group for study. NetworkAnalyst tool was used to construct gene regulatory network of DEGs, while DAVID and Metascape were utilized to perform gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of DEGs. The hub genes were screened by STRING and cytoscape, and the ONCOMINE, GEPIA, UALCAN, cBioPortal and HPA databases were used to analyze the expression differences and survival curves of UC at the DNA, RNA, protein levels and protein levels. TIMER was used to analyze the relationship between hub genes and immunocyte infiltration.Results In total, 63 DEGs were identified from the GEO database of UC, of which 31 and 32 were up-and down-regulated. GO/KEGG pathway analysis identified DEGs were mainly enriched in the collagen catabolic process, extracellular matrix (ECM) organization, ECM structural constituent and ECM-receptor interaction. Nine hub genes (i.e. COL1A1, COL1A2, COL3A1, COL5A2, MMP9, POSTN, SPP1, VCAN and THBS2) upregulated in invasive UC compared with superficial UC were identified. cBioportal database analysis showed that 35% of UC patients presented genetic variants in the hub genes, of which amplification and deletion mutations were the most common. ONCOMINE and UALCAN database analysis showed that the mRNA expression of all hub genes in invasive UC was significantly higher than that in superficial UC and normal tissues. HPA database analysis showed that there was up-regulation of COL3A1, SPP1, POSTN and VCAN protein in UC tissues than in normal tissues. GEPIA showed that COL1A2, COL3A1, THBS2, and VCAN were positively correlated with the OS rate among patients with UC (P < 0.05). UALCAN showed that UC patients with high expression of COL1A1, COL1A2, COL5A2 and POSTN had a poorer prognosis (P < 0.05). TRRUST database analysis indicated that there was a significant correlation between the expression of the hub genes and the infiltration of CD4 + T cells, CD8 + T cells, macrophages, neutrophils and dendritic cells.Conclusion Hub genes played important roles in pathogenesis and treatment prognosis of UC. Hub genes analysis provides new predictive biomolecules for UC immunotherapy and prognosis judgment.

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Identification of 9-Core Immune-Related Genes in Bladder Urothelial Carcinoma Prognosis

Cited by 21 publications

References 32 publications

Rac3 Expression and its Clinicopathological Significance in Patients With Bladder Cancer

Rac3 Expression and its Clinicopathological Significance in Patients With Bladder Cancer

Identification of Tumor Microenvironment-Related Alternative Splicing Events to Predict the Prognosis of Endometrial Cancer

Identification of Prognostic Biomarkers of Potential Hub Genes in Urothelial Carcinoma and Function in Microenvironment

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