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Identification of autophagy‐related genes signature predicts chemotherapeutic and immunotherapeutic efficiency in bladder cancer (BLCA)

机译:自噬相关基因签名的鉴定预测膀胱癌(BLCA)中的化疗和免疫治疗效率

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摘要

Autophagy maintains cellular homeostasis by degrading and recycling cytoplasmic components under stress conditions, which is identified to be involved in tumorigenesis and now has been recognized as novel target in cancer treatment. In present study, we gathered total autophagy‐related genes and established an autophagy‐related genes signature (ATGRS) through LASSO cox regression analysis in BLCA. Kaplan‐Meier survival and multivariate cox regression analyses both showed the ATGRS was a robust independent prognostic factor with high accuracy. Subsequently, integrated analyses indicated that ATGRS had a strong correlation with molecular subtypes, clinicopathological characteristics and somatic mutation alteration. Moreover, ATGRS was found to be positively correlated with the infiltration of immune cells in tumour microenvironment (TME) and immune checkpoint expression, indicating the potent role of autophagy by regulating the TME. In addition, ATGRS was proved to be efficient in predicting the clinical benefit of immune checkpoint inhibitors (ICIs) based immunotherapy and chemotherapy in BLCA. Furthermore, we observed abnormal expression levels of autophagy‐related genes and found the different behaviour of ATGRS in pancancer by LASSO cox regression analysis. Therefore, construction of ATGRS in BLCA could help us to interpret the underlying mechanism of autophagy and sheds a light on the clinical application for a combination of autophagy modification with targeted immunotherapy and chemotherapy in BLCA.
机译:自噬通过降解和再循环胁迫条件下的细胞质组分维持细胞稳态,鉴定涉及肿瘤发生,现在已经被认为是癌症治疗中的新靶标。在目前的研究中,我们通过BLCA中的洛杉矶COX回归分析建立了全自噬相关基因并建立了与自噬相关基因签名(Atgrs)。 Kaplan-Meier生存和多元COX回归分析都显示Atgrs是一种高精度的强大独立的预后因素。随后,集成分析表明,Atgrs与分子亚型,临床病理特征和体细胞突变改变具有强烈相关性。此外,发现atgrs与肿瘤微环境(TME)和免疫检查点表达中免疫细胞的浸润呈正相关,表明通过调节TME进行自噬的有效作用。此外,证明Atgrs有效地预测免疫检查点抑制剂(ICIS)的免疫疗法和化疗在BLCA中的临床益处。此外,我们观察到与卢斯Cox回归分析达索康乃伊中atgrs的异常表达水平。因此,在BLCA中的Atgrs的构建可以帮助我们解释自噬的潜在机制,并在临床应用中阐明临床应用,以便在BLCA中具有靶向免疫疗法和化疗的自噬改性。

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