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肿瘤浸润 M2 巨噬细胞可预测根治性前列腺切除术后局限性前列腺癌的生化复发。

Tumor infiltrating M2 macrophages could predict biochemical recurrence of localized prostate cancer after radical prostatectomy.

机构信息

Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.

Department of Urology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China.

出版信息

Exp Cell Res. 2019 Nov 1;384(1):111588. doi: 10.1016/j.yexcr.2019.111588. Epub 2019 Aug 29.

Abstract

Given the critical role of the tumor microenvironment in PCa progression, we aimed to assess the prognostic effect of tumor infiltrating M2 macrophages (TIMMs) on biochemical recurrence (BCR) in patients with localized prostate cancer (PCa) after radical prostatectomy. A total of 127 localized PCa patients from GSE116918, 268 patients from TCGA database and 77 patients from GSE70770 were enrolled in our study. TIMMs were evaluated by the CIBERSORT method. Patients with high TIMMs had a significantly poorer recurrence free survival (RFS) (P = 0.017, P = 0.0063 and P = 0.001) in the three sets. In the multivariate analysis, the presence of high TIMMs (HR = 3.026, P = 0.023; HR = 2.679, P = 0.017; HR = 2.648, P = 0.005) was identified as an independent prognostic factor for RFS in the three sets. Harrell's Concordance index (C-index) increased in all three sets after combining TIMMs with traditional risk factors (PSA, clinical stage(T) and Gleason score). Gene Set Enrichment Analysis showed that T cell receptor signaling pathway, B cell receptor signaling pathway and primary immunodeficiency were significantly enriched in the low TIMMs group. TIMMs could serve as an independent prognostic factor for BCR in localized PCa patients after RP. Incorporation of TIMMs into traditional risk classification might further stratify patients with different prognosis.

摘要

鉴于肿瘤微环境在前列腺癌(PCa)进展中的关键作用,我们旨在评估肿瘤浸润性 M2 巨噬细胞(TIMMs)对根治性前列腺切除术后局限性前列腺癌(PCa)患者生化复发(BCR)的预后影响。我们的研究共纳入了 GSE116918 中的 127 例局限性 PCa 患者、TCGA 数据库中的 268 例患者和 GSE70770 中的 77 例患者。通过 CIBERSORT 方法评估 TIMMs。在这三组患者中,TIMMs 高表达的患者无复发生存率(RFS)明显较差(P=0.017、P=0.0063 和 P=0.001)。在多变量分析中,高 TIMMs 的存在(HR=3.026,P=0.023;HR=2.679,P=0.017;HR=2.648,P=0.005)被确定为三组患者 RFS 的独立预后因素。在将 TIMMs 与传统危险因素(PSA、临床分期(T)和 Gleason 评分)相结合后,所有三组的 Harrell 一致性指数(C-index)均增加。基因集富集分析显示,低 TIMMs 组中 T 细胞受体信号通路、B 细胞受体信号通路和原发性免疫缺陷显著富集。TIMMs 可作为 RP 后局限性 PCa 患者 BCR 的独立预后因素。将 TIMMs 纳入传统风险分类可能进一步对具有不同预后的患者进行分层。

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