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βcatenin 是睾丸生殖细胞肿瘤中临床特征不良和免疫浸润受抑制的标志物。

βcatenin is a marker of poor clinical characteristics and suppressed immune infiltration in testicular germ cell tumors.

机构信息

2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Klenova 1, 833 10, Bratislava, Slovak Republic.

National Cancer Institute, Klenova 1, 833 10, Bratislava, Slovakia.

出版信息

BMC Cancer. 2018 Nov 3;18(1):1062. doi: 10.1186/s12885-018-4929-x.

DOI:10.1186/s12885-018-4929-x
PMID:30390643
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6215644/
Abstract

BACKGROUND

WNT/βcatenin (WNTβ) pathway is activated in early stages of embryonic development. We aimed to evaluate the significance of βcatenin in germ cell tumors (GCTs) and explore associations with the inflamed environment.

METHODS

Surgical specimens from 247 patients were analyzed. Βcatenin expression was detected in the tumor tissue by immunohistochemistry and correlated with clinical characteristics, outcome, PD-L1 expression and systemic immune-inflammation index (SII). The Ingenuity Pathway Analysis (IPA) was used to investigate the immune-cell related effects of βcatenin and PD-L1 encoding genes.

RESULTS

βcatenin was expressed in 86.2% of GCTs. The expression in seminomas was significantly lower compared to all subtypes of non-seminoma (all P <  0.0001). A high expression (weighted histoscore > 150) was associated with primary mediastinal non-seminoma (P = 0.035), intermediate/poor risk disease (P = 0.033) and high tumor markers (P = 0.035). We observed a positive correlation with the PD-L1 in tumor and an inverse correlation with the SII. IPA uncovered relationships of CTNNB (βcatenin) and CD274 (PD-L1) genes and their effects on differentiation, proliferation and activation of lymphocyte subtypes.

CONCLUSION

Herein, we showed that βcatenin is associated with male adult GCT characteristics as well as supressed immune environment.

摘要

背景

WNT/β连环蛋白（WNTβ）通路在胚胎发育的早期阶段被激活。我们旨在评估β连环蛋白在生殖细胞瘤（GCT）中的意义，并探索其与炎症环境的关联。

方法

分析了 247 名患者的手术标本。通过免疫组织化学检测肿瘤组织中β连环蛋白的表达，并将其与临床特征、预后、PD-L1 表达和全身性免疫炎症指数（SII）相关联。采用Ingenuity Pathway Analysis（IPA）分析β连环蛋白和 PD-L1 编码基因的免疫细胞相关效应。

结果

β连环蛋白在 86.2%的 GCT 中表达。精原细胞瘤中的表达明显低于所有非精原细胞瘤亚型（均 P<0.0001）。高表达（加权组织评分>150）与原发性纵隔非精原细胞瘤（P=0.035）、中/高危疾病（P=0.033）和高肿瘤标志物（P=0.035）相关。我们观察到与肿瘤 PD-L1 呈正相关，与 SII 呈负相关。IPA 揭示了 CTNNB（β连环蛋白）和 CD274（PD-L1）基因之间的关系及其对淋巴细胞亚型分化、增殖和激活的影响。

结论

本研究表明，β连环蛋白与男性成人 GCT 特征以及受抑制的免疫环境有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/480d/6215644/418ff0313efd/12885_2018_4929_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/480d/6215644/e6641495698f/12885_2018_4929_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/480d/6215644/418ff0313efd/12885_2018_4929_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/480d/6215644/e6641495698f/12885_2018_4929_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/480d/6215644/418ff0313efd/12885_2018_4929_Fig2_HTML.jpg

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