Comprehensive Analysis of Differential Gene Expression and Correlated Immune Infiltration in Bladder Cancer
Abstract
Background: Bladder cancer (BCa) is one of the most common urinary tract malignancies. Our study aimed to provide promising biomarkers for BCa screening and prognosis.
Methods: BCa samples were obtained from Gene Expression Omnibus (GEO) datasets. Differentially expressed genes (DEGs) were analysed by GO/KEGG analysis. Univariate Cox hazard analysis and Kaplan Meier Curve clarified the relevance of DEGs and survival. Receiver operating characteristic (ROC) curve showed the discrimination ability of DEGs in BCa patient outcome prediction. RT-PCR was used to validate gene expression.
Results: Overall, 61 common up regulated and 170 common down-regulated genes in BCa were obtained. DEGs were mainly enriched in proliferation and metastasis processes. CDC20, COL14A1, SPARCL1, TMOD1, RHOJ, FXYD6 and MFAP4 had clinical relevance to survival with high accuracy. CDC20, SPARCL1 and TMOD1 are promising biomarkers of BCa. CDC20, SPARCL1 and TMOD1 are involved in cancer immune infiltration.
Conclusion: CDC20, SPARCL1 and TMOD1 are promising biomarkers of bladder cancer. In addition, CDC20, SPARCL1 and TMOD1 are involved in cancer immune infiltration, which provides new targets in immune therapy in bladder cancer.
2. Gakis G (2020). Management of Muscle-invasive Bladder Cancer in the 2020s: Challenges and Perspectives. Eur Urol Focus, 6:632-638.
3. Guo CC, Czerniak B (2019). Bladder Cancer in the Genomic Era. Arch Pathol Lab Med, 143:695-704.
4. Puzio-Kuter AM, Castillo-Martin M, Kinkade CW, et al (2009). Inactivation of p53 and Pten promotes invasive bladder cancer. Genes Dev, 23:675-80.
5. Majid S, Saini S, Dahiya R (2012). Wnt signaling pathways in urological cancers: past decades and still growing. Mol Cancer, 11:7.
6. Luo H, Xu C, Le W, Ge B, Wang T (2019). lncRNA CASC11 promotes cancer cell proliferation in bladder cancer through miRNA-150. J Cell Biochem, 120:13487-13493.
7. Chen Y, Peng Y, Xu Z, et al (2019). Knockdown of lncRNA SNHG7 inhibited cell proliferation and migration in bladder cancer through activating Wnt/beta-catenin pathway. Pathol Res Pract, 215:302-307.
8. Zhao XL, Zhao ZH, Xu WC, et al (2015). Increased expression of SPRY4-IT1 predicts poor prognosis and promotes tumor growth and metastasis in bladder cancer. Int J Clin Exp Pathol, 8:1954-60.
9. Pan S, Zhan Y, Chen X, Wu B, Liu B (2019). Bladder Cancer Exhibiting High Immune Infiltration Shows the Lowest Response Rate to Immune Checkpoint Inhibitors. Front Oncol, 9:1101.
10. Livak KJ, Schmittgen TD (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods, 25:402-8.
11. McConkey DJ, Choi W, Marquis L, et al (2009). Role of epithelial-to-mesenchymal transition (EMT) in drug sensitivity and metastasis in bladder cancer. Cancer Metastasis Rev, 28:335-44.
12. Wang L, Zhang J, Wan L, et al (2015). Targeting Cdc20 as a novel cancer therapeutic strategy. Pharmacol Ther, 151:141-51.
13. Wang Z, Wan L, Zhong J, et al (2013). Cdc20: a potential novel therapeutic target for cancer treatment. Curr Pharm Des, 19:3210-4.
14. Harley ME, Allan LA, Sanderson HS, Clarke PR (2010). Phosphorylation of Mcl-1 by CDK1-cyclin B1 initiates its Cdc20-dependent destruction during mitotic arrest. EMBO J, 29:2407-20.
15. Qiao X, Zhang L, Gamper AM, Fujita T, Wan Y (2010). APC/C-Cdh1: from cell cycle to cellular differentiation and genomic integrity. Cell Cycle, 9:3904-12.
16. Li J, Wang X, Zheng K, et al (2019). The clinical significance of collagen family gene expression in esophageal squamous cell carcinoma. PeerJ, 7:e7705.
17. Hurley PJ, Marchionni L, Simons BW, et al (2012). Secreted protein, acidic and rich in cysteine-like 1 (SPARCL1) is down regulated in aggressive prostate cancers and is prognostic for poor clinical outcome. Proc Natl Acad Sci U S A, 109:14977-82.
18. Song Y, Fu Y, Xie Q, et al (2020). Anti-angiogenic Agents in Combination With Immune Checkpoint Inhibitors: A Promising Strategy for Cancer Treatment. Front Immunol, 11:1956.
19. Suttmann H, Riemensberger J, Bentien G, et al (2006). Neutrophil granulocytes are required for effective Bacillus Calmette-Guerin immunotherapy of bladder cancer and orchestrate local immune responses. Cancer Res, 66:8250-7.
20. Mantovani A, Sica A, Allavena P, et al (2009). Tumor-associated macrophages and the related myeloid-derived suppressor cells as a paradigm of the diversity of macrophage activation. Hum Immunol, 70:325-30.
Files | ||
Issue | Vol 52 No 6 (2023) | |
Section | Original Article(s) | |
DOI | https://doi.org/10.18502/ijph.v52i6.12988 | |
Keywords | ||
Bladder cancer Differentially expressed genes (DEGs) Network analysis Biomarker Immune infiltration |
Rights and permissions | |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |