Identification of tumor antigens and immune landscapes for bladder urothelial carcinoma mRNA vaccine.

Autor:	Sun Z; Department of Urology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China., Jing C; Faculty of Medicine, Ludwig Maximilian University of Munich (LMU), Munich, Germany.; Institute of Diabetes and Regeneration, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany., Zhan H; Department of Urology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China., Guo X; Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China., Suo N; Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China., Kong F; Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China., Tao W; Department of Urology, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China., Xiao C; Department of Urology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China., Hu D; Department of Urology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China., Wang H; Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China., Jiang S; Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 Jan 25; Vol. 14, pp. 1097472. Date of Electronic Publication: 2023 Jan 25 (Print Publication: 2023).
DOI:	10.3389/fimmu.2023.1097472
Abstrakt:	Background: Bladder urothelial carcinoma (BLCA) is associated with high mortality and recurrence. Although mRNA-based vaccines are promising treatment strategies for combating multiple solid cancers, their efficacy against BLCA remains unclear. We aimed to identify potential effective antigens of BLCA for the development of mRNA-based vaccines and screen for immune clusters to select appropriate candidates for vaccination. Methods: Gene expression microarray data and clinical information were retrieved from The Cancer Genome Atlas and GSE32894, respectively. The mRNA splicing patterns were obtained from the SpliceSeq portal. The cBioPortal for Cancer Genomics was used to visualize genetic alteration profiles. Furthermore, nonsense-mediated mRNA decay (NMD) analysis, correlation analysis, consensus clustering analysis, immune cell infiltration analysis, and weighted co-expression network analysis were conducted. Results: Six upregulated and mutated tumor antigens related to NMD, and infiltration of APCs were identified in patients with BLCA, including HP1BP3, OSBPL9, SSH3, ZCCHC8, FANCI, and EIF4A2. The patients were subdivided into two immune clusters (IC1 and IC2) with distinct clinical, cellular and molecular features. Patients in IC1 represented immunologically 'hot' phenotypes, whereas those in IC2 represented immunologically 'cold' phenotypes. Moreover, the survival rate was better in IC2 than in IC1, and the immune landscape of BLCA indicated significant inter-patient heterogeneity. Finally, CALD1, TGFB3, and ANXA6 were identified as key genes of BLCA through WGCNA analysis, and their mRNA expression levels were measured using qRT-PCR. Conclusion: HP1BP3, OSBPL9, SSH3, ZCCHC8, FANCI, and EIF4A2 were identified as potential antigens for developing mRNA-based vaccines against BLCA, and patients in IC2 might benefit more from vaccination. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Sun, Jing, Zhan, Guo, Suo, Kong, Tao, Xiao, Hu, Wang and Jiang.)
Databáze:	MEDLINE
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