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High ORAI3 expression correlates with good prognosis in human muscle-invasive bladder cancer.
- Source :
-
Gene [Gene] 2022 Jan 15; Vol. 808, pp. 145994. Date of Electronic Publication: 2021 Oct 07. - Publication Year :
- 2022
-
Abstract
- The involvement of store-operated calcium channels (SOCCs) in tumor initiation and metastatic dissemination has been extensively studied, but how its member ORAI3 influences tumor progression is still elusive. The present study aimed to evaluate the prognostic value of ORAI3 expression and examine the correlation between ORAI3 expression and immune cell infiltration within the tumor microenvironment (TME) in human muscle-invasive bladder cancer (MIBC). We examined the expression profile of ORAI3 in MIBC using data from two databases; analyzed the correlation between ORAI3 expression and patient survival; explored cellular pathways related to ORAI3 expression by Gene Set Enrichment Analysis (GSEA); and predicted potential drugs using Connectivity Map (CMap). ORAI3 was significantly lower expressed in tumor mass compared to normal samples in MIBC, with a higher level of methylation at the promoter region in tumor than in normal tissue, indicating that ORAI3 is suppressed during cancer progression. Survival analysis showed that higher expression of ORAI3 correlated with good prognosis in MIBC. GSEA demonstrated that ORAI3 expression inversely correlated with cell differentiation, development and gene silencing, with differential expression of genes involved in epidermal and keratinocyte differentiation pathways and inflammatory responses. RNA sequencing of an ORAI3-silenced human bladder cancer cell line (T24 cells) corroborated enhancement of pro-neoplastic pathways in absence of ORAI3. Western blottingMoreover, ORAI3 facilitated the recruitment of Th17 cells and natural killer cells, whereas hampered Th2 and macrophage infiltration. Our results revealed 4 molecules with potential to be beneficial as adjuvant drugs in MIBC treatment. We concluded that high ORAI3 expression correlates with increased survival in human MIBC.<br /> (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Subjects :
- Biomarkers, Tumor genetics
Calcium Channels metabolism
China
Databases, Genetic
Disease Progression
Gene Expression genetics
Gene Expression Regulation, Neoplastic genetics
Genetic Predisposition to Disease genetics
Humans
Neoplasm Invasiveness genetics
Prognosis
Survival Analysis
Transcriptome genetics
Tumor Microenvironment immunology
Urinary Bladder pathology
Calcium Channels genetics
Gene Expression Profiling methods
Urinary Bladder Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0038
- Volume :
- 808
- Database :
- MEDLINE
- Journal :
- Gene
- Publication Type :
- Academic Journal
- Accession number :
- 34626722
- Full Text :
- https://doi.org/10.1016/j.gene.2021.145994