Department of Urology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Faculty of Medicine, Ludwig Maximilian University of Munich (LMU), Munich, Germany.
Front Immunol. 2023 Jan 25;14:1097472. doi: 10.3389/fimmu.2023.1097472. eCollection 2023.
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.
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.
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.
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.
膀胱癌（BLCA）与高死亡率和高复发率相关。尽管基于 mRNA 的疫苗是治疗多种实体癌的有前途的治疗策略，但它们对 BLCA 的疗效仍不清楚。我们旨在鉴定 BLCA 的潜在有效抗原，用于开发基于 mRNA 的疫苗，并筛选免疫簇，以选择合适的疫苗接种候选者。
从癌症基因组图谱和 GSE32894 中分别检索基因表达微阵列数据和临床信息。从 SpliceSeq 门户获取 mRNA 剪接模式。使用癌症基因组学 cBioPortal 可视化遗传改变谱。此外，进行无意义介导的 mRNA 降解（NMD）分析、相关性分析、共识聚类分析、免疫细胞浸润分析和加权共表达网络分析。
在 BLCA 患者中发现了 6 个与 NMD 相关的上调和突变肿瘤抗原以及 APC 浸润，包括 HP1BP3、OSBPL9、SSH3、ZCCHC8、FANCI 和 EIF4A2。患者被分为具有不同临床、细胞和分子特征的两个免疫簇（IC1 和 IC2）。IC1 中的患者代表免疫“热”表型，而 IC2 中的患者代表免疫“冷”表型。此外，IC2 中的患者生存率优于 IC1，并且 BLCA 的免疫景观表明存在显著的患者间异质性。最后，通过 WGCNA 分析鉴定出 CALD1、TGFB3 和 ANXA6 是 BLCA 的关键基因，并通过 qRT-PCR 测量其 mRNA 表达水平。
HP1BP3、OSBPL9、SSH3、ZCCHC8、FANCI 和 EIF4A2 被鉴定为开发针对 BLCA 的基于 mRNA 的疫苗的潜在抗原，IC2 中的患者可能从疫苗接种中获益更多。
