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GBP2 作为肾细胞癌的新型预后生物标志物和潜在的免疫微环境指标

英文原题:GBP2 serves as a novel prognostic biomarker and potential immune microenvironment indicator in renal cell carcinoma.

查看英文原题

GBP2 serves as a novel prognostic biomarker and potential immune microenvironment indicator in renal cell carcinoma.

PubMed 2022/10/12(内容时间) Mol Carcinog Q2 · IF 3.5(JCR 2025)

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中文摘要

免疫检查点治疗(ICT)逐渐成为透明细胞肾细胞癌(ccRCC)治疗的新策略,因此需要能够预测个体对ICT反应的生物标志物。

本研究旨在寻找一种新的临床指标,用于ccRCC术后监测和ICT反应预测。我们利用公共数据库、临床标本和ccRCC细胞系,研究了GBP2表达及其与肿瘤微环境中免疫细胞浸润的关系。利用公共数据库进行的生物信息学分析显示,在包括ccRCC在内的多种癌症类型中,GBP2在癌组织中的表达高于癌旁正常组织,通过Western Blot和PCR检测临床组织样本也获得了相同结果。在ccRCC细胞系中,CCK-8增殖实验和凋亡评估提示GBP2促进ccRCC的恶性程度。286例ccRCC患者被随机分为训练队列或验证队列,免疫组化(IHC)和Kaplan-Meier分析显示,GBP2高表达与更差预后相关。C-index分析表明,将GBP2表达与TNM分期整合,相比单独使用任一指标,可提高预测ccRCC患者预后的准确性。生物信息学分析提示GBP2与免疫之间存在关系,且GBP2表达与ccRCC微环境中的抑制性免疫标志物呈正相关。

综上所述,我们的研究表明GBP2有潜力作为ccRCC的预后预测指标,并观察到GBP2与ccRCC中TIL(肿瘤浸润淋巴细胞)之间的关联,使其成为预测ICT反应的有前景的指标。

展开英文摘要原文

Since the application of immune checkpoint therapy (ICT) has gradually become a new strategy for clear cell renal cell carcinoma (ccRCC) treatment, biomarkers that predict the individual response to ICT is needed.

This study aimed to identify a new clinical indicator for postoperative surveillance of ccRCC and prediction of ICT response.

We investigated the GBP2 expression and its relation with immune cell infiltration in tumor microenvironment using public databases, clinical specimens and ccRCC cell lines. Bioinformatic analysis using public database revealed that GBP2 expression is higher in cancer tissues than in adherent normal tissues among different cancer types including ccRCC, and the same results were acquired from clinical tissue samples tested by Western Blot and PCR. In ccRCC cell lines, CCk-8 proliferation assay and apoptosis assessment suggested GBP2 facilitates the malignancy of ccRCC. 286 ccRCC patients were randomly divided into a training or validation cohort, and immunohistochemistry (IHC) and Kaplan-Meier analysis revealed that higher GBP2 expression is related to worse prognosis.

C-index analysis implied that integrating GBP2 expression with TNM stage improved the accuracy in predicting prognosis of ccRCC patients compared to the solitary use of either. Bioinformatic analysis implied a relation between GBP2 and immunity, and GBP2 expression is positively related with suppressive immune markers in ccRCC microenvironment.

Taken together, our study demonstrated the potential of GBP2 to sever as a prognostic predictor of ccRCC, and an association between GBP2 and tumor-infiltrating lymphocytes in ccRCC was observed, making it a promising indicator of ICT response.

论文信息

作者
Tian Y、Wang H、Guan W、Tu X、Zhang X、Sun Y、Qian C、Song X
单位
Department of Urinary Surgery, The Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai, China.China
文献类型
随机对照试验 · 非美国政府资助研究
期刊
Molecular carcinogenesis2022 Dec
原文标识
PubMed 36222186 · DOI 10.1002/mc.23447