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作为肾透明细胞癌的一种预后生物标志物和潜在治疗靶点。

as a prognostic biomarker and potential therapeutic target in kidney renal clear cell carcinoma.

作者信息

Zou Tao, Jia Zongming, Wu Jixiang, Liu Xuxu, Deng Minghao, Zhang Xuefeng, Lin Yuxin, Ping Jigen

机构信息

Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, China.

Department of Neurology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.

出版信息

Front Immunol. 2024 Dec 17;15:1521629. doi: 10.3389/fimmu.2024.1521629. eCollection 2024.

Abstract

BACKGROUND

Progestin And AdipoQ Receptor Family Member VI () plays a significant role in the non-genomic effects of rapid steroid responses and is abnormally expressed in various tumors. However, its biological function in kidney renal clear cell carcinoma (KIRC) and its potential as a therapeutic target remain underexplored.

METHODS

In this study, was identified as a critical oncogene by WGCNA algorithm and differential gene expression analysis using TCGA - KIRC and GSE15641 data. The differences in expression and its association with KIRC survival outcomes were investigated, and transcriptomic data were used to further elucidate 's biological functions. Moreover, XCELL and single - cell analysis assessed the correlation between expression and immune infiltration. TIDE algorithm was used to assess how well various patient cohorts responded to immune checkpoint therapy. Finally, the role of in the development of KIRC was verified through EdU, scratch assays, and Transwell assays.

RESULTS

Our findings suggest that elevated expression of is linked to a poor prognosis for KIRC patients. Functional enrichment analysis demonstrated that is primarily involved in angiogenesis and pluripotent stem cell differentiation, which are crucial in mediating the development of KIRC. Additionally, we established a ceRNA network that is directly related to overall prognosis, further supporting the role of as a prognostic biomarker for KIRC.

CONCLUSION

Using both computational and experimental methods, this study leads the charge in discovering and verifying as a prognostic biomarker and possible therapeutic target for KIRC. In the future, to determine its molecular mechanism in KIRC carcinogenesis, more research will be carried out.

摘要

背景

孕激素与脂联素受体家族成员VI()在类固醇快速反应的非基因组效应中起重要作用,且在多种肿瘤中异常表达。然而,其在肾透明细胞癌(KIRC)中的生物学功能及其作为治疗靶点的潜力仍未得到充分探索。

方法

在本研究中,通过加权基因共表达网络分析(WGCNA)算法以及使用TCGA - KIRC和GSE15641数据进行差异基因表达分析,确定为关键癌基因。研究了表达差异及其与KIRC生存结果的关联,并利用转录组数据进一步阐明的生物学功能。此外,通过XCELL和单细胞分析评估表达与免疫浸润之间的相关性。使用肿瘤免疫功能障碍和排除(TIDE)算法评估不同患者队列对免疫检查点治疗的反应程度。最后,通过EdU、划痕试验和Transwell试验验证在KIRC发生发展中的作用。

结果

我们的研究结果表明,表达升高与KIRC患者的预后不良相关。功能富集分析表明,主要参与血管生成和多能干细胞分化,这在介导KIRC的发展中至关重要。此外,我们建立了一个与总体预后直接相关的竞争性内源性RNA(ceRNA)网络,进一步支持作为KIRC预后生物标志物的作用。

结论

本研究采用计算和实验方法,率先发现并验证作为KIRC的预后生物标志物和可能的治疗靶点。未来,为确定其在KIRC致癌过程中的分子机制,将开展更多的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54f0/11685228/44796451861a/fimmu-15-1521629-g001.jpg

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