Wang Chuang, Wan Honglei, Zhang Han, Yang Bo, Huang Wen-Kuan, Sun Wenguo
Department of Urology, Guilin People's Hospital, Guilin, China.
Department of Urology, Handan First Hospital, Handan, China.
Front Cell Dev Biol. 2022 Jun 17;10:915798. doi: 10.3389/fcell.2022.915798. eCollection 2022.
The role of ligand-receptor (LR) pairs in disease progression has been explored in bladder cancer. However, the relationship of LR pairs with cancer prognosis and treatment response remains poorly understood. We characterized the LR pair network and identified three distinct molecular subtypes with distinct biologic features based on the TCGA database ( = 406) and validated in GSE13507 ( = 165) and GSE32894 ( = 224). Three subtypes were compared for differences in patient clinical characteristics, genomic, and transcriptomic features. A multivariate Lasso Cox regression model was applied to construct an LR pairs-based scoring model to stratify the prognostic risk of patients. We demonstrated the high LR. score patients had better responses in chemotherapy, while low LR. score patients may benefit from immune checkpoint blockade (ICB). Collectively, we identified three LR pair-related subtypes associated with prognosis. We constructed and validated a LR pairs-based gene signature, which helps to predict prognosis and differentiate the susceptible population to chemotherapy and immunotherapy in patients with bladder cancer. Among the LR pairs significantly related to prognosis, ANAX1-EGFR axis was found to be potential therapeutic target for treatment of bladder cancer.
配体-受体（LR）对在膀胱癌疾病进展中的作用已得到研究。然而，LR对与癌症预后及治疗反应之间的关系仍知之甚少。我们基于TCGA数据库（n = 406）对LR对网络进行了特征描述，并鉴定出具有不同生物学特征的三种不同分子亚型，且在GSE13507（n = 165）和GSE32894（n = 224）中进行了验证。比较了三种亚型在患者临床特征、基因组和转录组特征方面的差异。应用多变量Lasso Cox回归模型构建基于LR对的评分模型，以分层患者的预后风险。我们证明高LR评分患者对化疗反应更好，而低LR评分患者可能从免疫检查点阻断（ICB）中获益。总体而言，我们鉴定出与预后相关的三种LR对相关亚型。我们构建并验证了基于LR对的基因特征，其有助于预测膀胱癌患者的预后，并区分对化疗和免疫治疗敏感的人群。在与预后显著相关的LR对中，发现ANAX1-EGFR轴是治疗膀胱癌的潜在治疗靶点。
