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成纤维细胞生长因子结合蛋白 1 作为一种潜在的膀胱癌卡介苗反应预测生物标志物。

FGFBP1 as a potential biomarker predicting bacillus Calmette-Guérin response in bladder cancer.

机构信息

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

School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.

出版信息

Front Immunol. 2022 Sep 2;13:954836. doi: 10.3389/fimmu.2022.954836. eCollection 2022.

Abstract

Accurate prediction of Bacillus Calmette-Guérin (BCG) response is essential to identify bladder cancer (BCa) patients most likely to respond sustainably, but no molecular marker predicting BCG response is available in clinical routine. Therefore, we first identified that fibroblast growth factor binding protein 1 (FGFBP1) was upregulated in failures of BCG therapy, and the increased FGFBP1 had a poor outcome for BCa patients in the E-MTAB-4321 and GSE19423 datasets. These different expression genes associated with FGFBP1 expression are mainly involved in neutrophil activation, neutrophil-mediated immunity, and tumor necrosis factor-mediated signal pathways in biological processes. A significant positive correlation was observed between FGFBP1 expression and regulatory T-cell (Treg) infiltration by the Spearman correlation test in the BCG cohort ( = 0.177) and The Cancer Genome Atlas (TCGA) cohort ( = 0.176), suggesting that FGFBP1 may influence the response of BCa patients to BCG immunotherapy through immune escape. Though FGFBP1 expression was positively correlated with the expressions of PD-L1, CTLA4, and PDCD1 in TCGA cohort, a strong association between FGFBP1 and PD-L1 expression was only detected in the BCG cohort ( = 0.750). Furthermore, elevated FGFBP1 was observed in BCa cell lines and tissues in comparison to corresponding normal controls by RT-qPCR, Western blotting, and immunohistochemical staining. Increased FGFBP1 was further detected in the failures than in the responders by immunohistochemical staining. Notably, FGFBP1 is positively associated with PD-L1 expression in BCa patients with BCG treatment. To sum up, FGFBP1 in BCa tissue could be identified as a promising biomarker for the accurate prediction of BCG response in BCa.

摘要

准确预测卡介苗(BCG)反应对于确定最有可能持续反应的膀胱癌(BCa)患者至关重要,但目前临床常规中尚无预测 BCG 反应的分子标志物。因此,我们首先发现,成纤维细胞生长因子结合蛋白 1(FGFBP1)在 BCG 治疗失败中上调,并且在 E-MTAB-4321 和 GSE19423 数据集中,增加的 FGFBP1 对 BCa 患者的预后不良。与 FGFBP1 表达相关的这些不同表达基因主要涉及生物过程中的中性粒细胞激活、中性粒细胞介导的免疫和肿瘤坏死因子介导的信号通路。通过 Spearman 相关检验,在 BCG 队列( = 0.177)和癌症基因组图谱(TCGA)队列中观察到 FGFBP1 表达与调节性 T 细胞(Treg)浸润之间存在显著正相关( = 0.176),表明 FGFBP1 可能通过免疫逃避影响 BCa 患者对 BCG 免疫治疗的反应。尽管在 TCGA 队列中,FGFBP1 表达与 PD-L1、CTLA4 和 PDCD1 的表达呈正相关,但仅在 BCG 队列中检测到 FGFBP1 与 PD-L1 表达之间的强相关性( = 0.750)。此外,通过 RT-qPCR、Western blot 和免疫组织化学染色,与相应的正常对照相比,BCa 细胞系和组织中 FGFBP1 的表达升高。通过免疫组织化学染色进一步检测到失败组中 FGFBP1 的表达高于反应组。值得注意的是,在接受 BCG 治疗的 BCa 患者中,FGFBP1 与 PD-L1 表达呈正相关。总之,BCa 组织中的 FGFBP1 可作为预测 BCa 患者 BCG 反应的有前途的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aec5/9478507/111271366ad2/fimmu-13-954836-g001.jpg

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