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失巢凋亡相关基因影响膀胱癌的预后和肿瘤微环境。

Anoikis-Related Genes Impact Prognosis and Tumor Microenvironment in Bladder Cancer.

作者信息

Zhang Tao, Chen Shaojun, Qu Shanna, Wang Longsheng

机构信息

Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, China.

Cheeloo College of Medicine, Shandong University, Jinan, 250012, China.

出版信息

Mol Biotechnol. 2024 Aug 22. doi: 10.1007/s12033-024-01255-x.

Abstract

Anoikis tolerance is an important biological process of tumor colonization and metastasis outside the primary tumor. Recent research has progressively elucidated the function and underlying mechanisms of anoikis in the metastasis of various solid tumors. Nevertheless, the specific mechanisms of anoikis in bladder cancer and its consequent effects on the tumor immune microenvironment remain ambiguous. In this study, we developed an anoikis score based on five genes (ETV7, NGF, SCD, LAMC1, and CASP6) and categorized subjects into high and low-risk groups using the median score from the TCGA database. Our findings indicate that SCD enhances the proliferation of bladder cancer cells in vitro. Furthermore, integrating the anoikis score with clinicopathological features to construct a prognostic nomogram demonstrated precision in assessing patient outcomes. Immune cell analysis revealed elevated infiltration levels of Treg cells and M2 macrophages in the high anoikis score group, whereas CD8 T cell levels were reduced. This study highlights the importance of anoikis score in predicting patient prognosis, immune cell infiltration, and drug response, which may provide a treatment modality worth exploring in depth for the study of bladder cancer.

摘要

失巢凋亡耐受是肿瘤在原发肿瘤外定植和转移的重要生物学过程。近年来的研究逐步阐明了失巢凋亡在各种实体瘤转移中的作用及其潜在机制。然而,失巢凋亡在膀胱癌中的具体机制及其对肿瘤免疫微环境的影响仍不明确。在本研究中,我们基于五个基因(ETV7、NGF、SCD、LAMC1和CASP6)开发了一个失巢凋亡评分,并使用来自TCGA数据库的中位数评分将受试者分为高风险组和低风险组。我们的研究结果表明,SCD在体外可增强膀胱癌细胞的增殖。此外,将失巢凋亡评分与临床病理特征相结合构建的预后列线图在评估患者预后方面显示出准确性。免疫细胞分析显示,在高失巢凋亡评分组中,调节性T细胞和M2巨噬细胞的浸润水平升高,而CD8 T细胞水平降低。本研究强调了失巢凋亡评分在预测患者预后、免疫细胞浸润和药物反应方面的重要性,这可能为膀胱癌研究提供一种值得深入探索的治疗模式。

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