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表达KRT13的上皮细胞群体预示着膀胱癌对化疗和免疫治疗有更好的反应:基于膀胱癌数据库的综合证据

KRT13-expressing epithelial cell population predicts better response to chemotherapy and immunotherapy in bladder cancer: Comprehensive evidences based on BCa database.

作者信息

Yu Donghu, Chen Chen, Sun Le, Wu Shaojie, Tang Xiaoyu, Mei Liye, Lei Cheng, Wang Du, Wang Xinghuan, Cheng Liang, Li Sheng

机构信息

Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China; Department of Biological Repositories, Cancer Precision Diagnosis and Treatment and Translational Medicine Hubei Engineering Research Center, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.

Department of Biological Repositories, Cancer Precision Diagnosis and Treatment and Translational Medicine Hubei Engineering Research Center, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.

出版信息

Comput Biol Med. 2023 May;158:106795. doi: 10.1016/j.compbiomed.2023.106795. Epub 2023 Mar 21.

Abstract

Neoadjuvant chemotherapy (NAC) prior to surgery and immune checkpoint therapy (ICT) has revolutionized bladder cancer (BCa) treatment. Patients likely to benefit from these therapies need to be accurately stratified; however, this remains a major clinical challenge. In the present study, single-cell RNA sequencing was used to evaluate the predictive ability of an epithelial cell population highly expressing keratin 13 (KRT13) to assess therapeutic response in BCa. The presence of KRT13-enriched tumors indicated favorable outcomes after NAC and superior response to ICT in patients with BCa. Furthermore, KRT13 population characteristics appeared to be closely related to changes in the immune microenvironment in the vicinity of this cell population. We constructed a prognostic model using an artificial neural network based on the gene signatures in the KRT13 population; the model demonstrated strong robustness and superiority. Additionally, a user-friendly and open-access web application named BCa database was developed for researchers to study BCa by mining the connective map database.

摘要

手术前的新辅助化疗(NAC)和免疫检查点疗法(ICT)彻底改变了膀胱癌(BCa)的治疗方式。可能从这些疗法中获益的患者需要进行准确分层;然而,这仍然是一项重大的临床挑战。在本研究中,单细胞RNA测序被用于评估高表达角蛋白13(KRT13)的上皮细胞群体对BCa治疗反应的预测能力。富含KRT13的肿瘤的存在表明BCa患者在接受NAC后预后良好,对ICT的反应更佳。此外,KRT13群体特征似乎与该细胞群体附近免疫微环境的变化密切相关。我们基于KRT13群体中的基因特征,使用人工神经网络构建了一个预后模型;该模型显示出强大的稳健性和优越性。此外,还开发了一个名为BCa数据库的用户友好型开放获取网络应用程序,供研究人员通过挖掘连接图谱数据库来研究BCa。

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