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Specific subsets of urothelial bladder carcinoma infiltrating T cells associated with poor prognosis.

ABSTRACT: Comprehensive investigation of tumor-infiltrating lymphocytes in cancer is crucial to explore the effective immunotherapies, but the composition of infiltrating T cells in urothelial bladder carcinoma (UBC) remains elusive. Here, single-cell RNA sequencing (scRNA-seq) were performed on total 30,905 T cells derived from peripheral blood, adjacent normal and tumor tissues from two UBC patients. We identified 18 distinct T cell subsets based on molecular profiles and functional properties. Specifically, exhausted T (T_Ex) cells, exhausted NKT (NKT_Ex) cells, Ki67⁺ T cells and B cell-like T (B-T) cells were exclusively enriched in UBC. Additionally, the gene signatures of T_Ex, NKT_Ex, Ki67⁺ T and B-T cells were significantly associated with poor survival in patients with BC and various tumor types. Finally, IKZF3 and TRGC2 are the potential biomarkers of T_Ex cells. Overall, our study demonstrated an exhausted context of T cells in UBC, which layed a theoretical foundation for the development of effective tumor immunotherapies.

SUBMITTER: Guo R

PROVIDER: S-EPMC10406853 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Specific subsets of urothelial bladder carcinoma infiltrating T cells associated with poor prognosis.

Guo Rui R Wang Luyao L Bai Suhang S Kang Danyue D Zhang Wei W Ding Zhenshan Z Xing Tianying T Hao Mingxuan M Liang Youfeng Y Jiao Binbin B Zhang Guan G Ying Lu L Chen Ruolan R Chen Xiaoyang X Zhang Wenjing W Wang Jiansong J Wan Chuanxing C Yu Changyuan C Wang Haifeng H Yang Zhao Z

Scientific reports 20230807 1

Comprehensive investigation of tumor-infiltrating lymphocytes in cancer is crucial to explore the effective immunotherapies, but the composition of infiltrating T cells in urothelial bladder carcinoma (UBC) remains elusive. Here, single-cell RNA sequencing (scRNA-seq) were performed on total 30,905 T cells derived from peripheral blood, adjacent normal and tumor tissues from two UBC patients. We identified 18 distinct T cell subsets based on molecular profiles and functional properties. Specific ...[more]

PMID: 37550396

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Project description:Pentatricopeptide repeat domain 1 (PTCD1) was reported to regulate mitochondrial metabolism and oxidative phosphorylation. However, the effect and mechanism of PTCD1 in the development of bladder urothelial carcinoma (BLCA) remain unclear. The databases from The Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) were used to analyze the expression changes, clinical features, and prognostic values of PTCD1. A nomogram was built to predict the prognostic outcomes of BLCA cases. The potential genes interacting with PTCD1 were explored by Weighted Gene Coexpression Network Analysis (WGCNA). The estimation of associations between PTCD1 and tumor mutations, tumor immunities, and m6A methylations was performed. The study found that the gradual decrease of PTCD1 expression was observed with the increase of stage and grade. Low PTCD1 expression was greatly correlated with higher pathological stage, N stage, and poor prognosis in TCGA cohorts; interestingly, low-grade BLCA cases all exhibited high expression of PTCD1. HPA database analysis implied that the expression of PTCD1 protein in BLCA was lower than that in normal bladder tissue, and the protein expression of PTCD1 in high-grade BLCA was lower than that in low-grade BLCA. Multivariate Cox regression analysis indicated that PTCD1 may serve as an independent factor influencing prognosis of BLCA. Mechanistically, PTCD1 played a regulatory role in BLCA progression through multiple tumor-related pathways containing PI3K-Akt signaling, ECM-receptor interaction, oxidative phosphorylation, and extracellular matrix organization. WGCNA reported that PTCD1 had a strong positive correlation with POLR2J, ZNHT1, ATP5MF, PDAP1, BUD31, and COPS6. Besides, the mRNA expression of PTCD1 was negatively associated with immune cells' infiltrations, immune functions, and checkpoints, especially with some m6A methylation regulators in BLCA. In sum, downregulation of PTCD1 expression may be involved in the development of BLCA and remarkably correlated with poor prognosis. Meantime, it showed an influence in immune cell infiltration and may serve as an agreeable prognostic indicator in BLCA.

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Specific subsets of urothelial bladder carcinoma infiltrating T cells associated with poor prognosis.

Publications

Specific subsets of urothelial bladder carcinoma infiltrating T cells associated with poor prognosis.

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