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鉴定一种用于预测前列腺癌预后和评估肿瘤免疫微环境的基底膜基因特征。

Identification of a basement membrane gene signature for predicting prognosis and estimating the tumor immune microenvironment in prostate cancer.

作者信息

Xie Tao, Fu Du-Jiang, Li Kang-Jing, Guo Jia-Ding, Xiao Zhao-Ming, Li Zhijie, Zhao Shan-Chao

机构信息

Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.

Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510500, China.

出版信息

Aging (Albany NY). 2024 Jan 17;16(2):1581-1604. doi: 10.18632/aging.205445.

Abstract

Basement membrane plays an important role in tumor invasion and metastasis, which is closely related to prognosis. However, the prognostic value and biology of basement membrane genes (BMGs) in prostate cancer (PCa) remain unknown. In the TCGA training set, we used differentially expressed gene analysis, protein-protein interaction networks, univariate and multivariate Cox regression, and least absolute shrinkage and selection operator regression to construct a basement membrane-related risk model (BMRM) and validated its effectiveness in the MSKCC validation set. Furthermore, the accurate nomogram was constructed to improve clinical applicability. Patients with PCa were divided into high-risk and low-risk groups according to the optimal cut-off value of the basement membrane-related risk score (BMRS). It was found that BMRS was significantly associated with RFS, T-stage, Gleason score, and tumor microenvironmental characteristics in PCa patients. Further analysis showed that the model grouping was closely related to tumor immune microenvironment characteristics, immune checkpoint inhibitors, and chemotherapeutic drug sensitivity. In this study, we developed a new BMGs-based prognostic model to determine the prognostic value of BMGs in PCa. Finally, we confirmed that THBS2, a key gene in BMRM, may be an important link in the occurrence and progression of PCa. This study provides a novel perspective to assess the prognosis of PCa patients and provides clues for the selection of future personalized treatment regimens.

摘要

基底膜在肿瘤侵袭和转移中起重要作用,这与预后密切相关。然而,基底膜基因(BMGs)在前列腺癌(PCa)中的预后价值和生物学特性仍不清楚。在TCGA训练集中,我们使用差异表达基因分析、蛋白质-蛋白质相互作用网络、单变量和多变量Cox回归以及最小绝对收缩和选择算子回归来构建基底膜相关风险模型(BMRM),并在MSKCC验证集中验证了其有效性。此外,构建了精确的列线图以提高临床适用性。根据基底膜相关风险评分(BMRS)的最佳临界值,将PCa患者分为高风险组和低风险组。结果发现,BMRS与PCa患者的无复发生存期(RFS)、T分期、Gleason评分和肿瘤微环境特征显著相关。进一步分析表明,模型分组与肿瘤免疫微环境特征、免疫检查点抑制剂和化疗药物敏感性密切相关。在本研究中,我们开发了一种基于BMGs的新预后模型,以确定BMGs在PCa中的预后价值。最后,我们证实BMRM中的关键基因THBS2可能是PCa发生和进展的重要环节。本研究为评估PCa患者的预后提供了新的视角,并为未来个性化治疗方案的选择提供了线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f61/10866409/ace7dbd2c365/aging-16-205445-g001.jpg

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