机构：[1]The Second Affiliated Hospital, Hengyang Medical School, 34706University of South China, Hengyang, China.[2]504354The Third Xiangya Hospital of Central South University, Changsha, Hunan, PR China.[3]22494Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, USA.[4]Sichuan Cancer Center, School of Medicine, Sichuan Cancer Hospital and Institute, University of Electronic Science and Technology of China, Chengdu, China.四川省肿瘤医院[5]School of Basic Medical Sciences, 58305Fudan University, Shanghai, China.[6]International Center for Translational Chinese Medicine, Sichuan Academy of Chinese Medicine Sciences, Chengdu, China.
Objectives: Bladder cancer is the fourth most common malignancy in men in the United States. Aberrant alternative splicing (AS) events are involved in the carcinogenesis, but the association between AS and bladder cancer remains unclear. This study aimed to construct an AS-based prognostic signature and elucidate the role of the tumor immune microenvironment (TIME) and the response to immunotherapy and chemotherapy in bladder cancer. Methods: Univariate Cox regression analysis was performed to detect prognosis-related AS events. The least absolute shrinkage and selection operator (LASSO) and multivariate Cox analyses were employed to build prognostic signatures. Kaplan-Meier survival analysis, multivariate Cox regression analysis, and receiver operating characteristic (ROC) curves were conducted to validate the prognostic signatures. Then, the Estimation of Stromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) and tumor immune estimation resource (TIMER) databases were searched and the single-sample gene set enrichment analysis (ssGSEA) algorithm and CIBERSORT method were performed to uncover the context of TIME in bladder cancer. The Tumor Immune Dysfunction and Exclusion (TIDE) web tool and pRRophetic algorithm were used to predict the response to immunotherapy and chemotherapy. Finally, we constructed a correlation network between splicing factors (SFs) and survival-related AS events. Results: A total of 4684 AS events were significantly associated with overall survival in patients with bladder cancer. Eight prognostic signatures of bladder cancer were established, and a clinical survival prediction model was built. In addition, the consolidated prognostic signature was closely related to immune infiltration and the response to immunotherapy and chemotherapy. Furthermore, the correlation identified EIF3A, DDX21, SDE2, TNPO1, and RNF40 as hub SFs, and function analysis found ubiquitin-mediated proteolysis is correlated most significantly with survival-associated AS events. Conclusion: Our findings highlight the prognostic value of AS for patients with bladder cancer and reveal pivotal players of AS events in the context of TIME and the response to immunotherapy and chemotherapy, which may be important for patient management and treatment.
基金：
Health Commission’s
Scientific Research Program of Hunan Province (202204074707) to
Zhihong Xiao and the Health and Family Planning Commission of
Wuhan Municipality (WX18C29) to Zhihong Xiao.
第一作者机构：[1]The Second Affiliated Hospital, Hengyang Medical School, 34706University of South China, Hengyang, China.
共同第一作者：
通讯作者：
通讯机构：[1]The Second Affiliated Hospital, Hengyang Medical School, 34706University of South China, Hengyang, China.[3]22494Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, USA.[6]International Center for Translational Chinese Medicine, Sichuan Academy of Chinese Medicine Sciences, Chengdu, China.[*1]The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421000, China[*2]Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, 90001, USA
推荐引用方式(GB/T 7714)：
Chen Jiang,Liao Yangjie,Li Rui,et al.Immunotherapeutic Significance of a Prognostic Alternative Splicing Signature in Bladder Cancer.[J].TECHNOLOGY IN CANCER RESEARCH & TREATMENT.2022,21:doi:10.1177/15330338221090093.
APA：
Chen Jiang,Liao Yangjie,Li Rui,Luo Mingjiang,Wu Guanlin...&Xiao Zhihong.(2022).Immunotherapeutic Significance of a Prognostic Alternative Splicing Signature in Bladder Cancer..TECHNOLOGY IN CANCER RESEARCH & TREATMENT,21,
MLA：
Chen Jiang,et al."Immunotherapeutic Significance of a Prognostic Alternative Splicing Signature in Bladder Cancer.".TECHNOLOGY IN CANCER RESEARCH & TREATMENT 21.(2022)
