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评估原钙黏蛋白相关蛋白作为肾细胞癌预后和治疗反应的生物标志物。

Evaluating trophinin associated protein as a biomarker of prognosis and therapy response in renal cell carcinoma.

机构信息

Department of Oncology, Dongguan Key Laboratory of Precision Diagnosis and Treatment for Tumors, Dongguan Institute of Clinical Cancer Research, The Tenth Affiliated Hospital of Southern Medical University (Dongguan people's hospital), Dongguan, 523059, China.

Department of Pulmonary & Critical Care Medicine, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Dongguan, 523059, China.

出版信息

BMC Cancer. 2024 Aug 17;24(1):1021. doi: 10.1186/s12885-024-12802-9.

DOI:10.1186/s12885-024-12802-9
PMID:39153983
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11330045/
Abstract

BACKGROUND

Trophinin Associated Protein (TROAP) has been implicated in some tumors, yet its role in renal cell carcinoma (RCC) remains underexplored. This study aims to elucidate the prognostic and therapeutic implications of TROAP in RCC, encompassing different subtypes.

METHODS

Firstly, we identified the expression patterns of TROAP across various tumors within the TCGA pan-cancer cohort. Subsequently, the prognostic significance of TROAP was validated in three TCGA RCC cohorts and a local cohort. Finally, we conducted functional enrichment analysis, somatic mutations and copy number variations, assessed therapeutic response cohorts, and performed in vitro experiments to explore the biological characteristics of TROAP.

RESULTS

TROAP serves as an unfavorable factor in both the TCGA RCC datasets and our local cohort. Functional enrichment analysis and in vitro experiments have demonstrated its oncogene effect in promoting tumor progression. Additionally, the relationship between TROAP expression and gene mutations in RCC appears to be limited. Furthermore, elevated TROAP expression is associated with reduced efficacy of RCC therapies, including nivolumab and everolimus.

CONCLUSIONS

Our findings illustrate TROAP as a pivotal biomarker for prognosis and therapeutic response in RCC. Elevated TROAP expression is indicative of aggressive tumor behavior and resistance to conventional therapies, making it a valuable target for personalized treatment strategies in RCC management.

摘要

背景

Trophinin 相关蛋白(TROAP)已被发现与一些肿瘤有关,但它在肾细胞癌(RCC)中的作用仍未得到充分探索。本研究旨在阐明 TROAP 在 RCC 不同亚型中的预后和治疗意义。

方法

首先,我们在 TCGA 泛癌症队列中鉴定了 TROAP 在各种肿瘤中的表达模式。随后,在三个 TCGA RCC 队列和一个本地队列中验证了 TROAP 的预后意义。最后,我们进行了功能富集分析、体细胞突变和拷贝数变异分析,评估了治疗反应队列,并进行了体外实验,以探讨 TROAP 的生物学特性。

结果

TROAP 在 TCGA RCC 数据集和我们的本地队列中均作为不利因素。功能富集分析和体外实验表明,它作为一种致癌基因,促进了肿瘤的进展。此外,TROAP 表达与 RCC 中基因突变之间的关系似乎有限。此外,TROAP 表达水平升高与 RCC 治疗的疗效降低有关,包括 nivolumab 和 everolimus。

结论

我们的研究结果表明,TROAP 是 RCC 预后和治疗反应的关键生物标志物。TROAP 表达水平升高提示肿瘤行为具有侵袭性且对常规治疗具有耐药性,因此,TROAP 是 RCC 个体化治疗策略的一个有价值的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c49/11330045/2ed75cdf77ef/12885_2024_12802_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c49/11330045/a144960fead6/12885_2024_12802_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c49/11330045/dfb61e6d26d8/12885_2024_12802_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c49/11330045/13d21c291c97/12885_2024_12802_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c49/11330045/7173f1e8eb75/12885_2024_12802_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c49/11330045/23d6002b6d39/12885_2024_12802_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c49/11330045/1808c664af88/12885_2024_12802_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c49/11330045/2ed75cdf77ef/12885_2024_12802_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c49/11330045/a144960fead6/12885_2024_12802_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c49/11330045/dfb61e6d26d8/12885_2024_12802_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c49/11330045/13d21c291c97/12885_2024_12802_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c49/11330045/7173f1e8eb75/12885_2024_12802_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c49/11330045/23d6002b6d39/12885_2024_12802_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c49/11330045/1808c664af88/12885_2024_12802_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c49/11330045/2ed75cdf77ef/12885_2024_12802_Fig7_HTML.jpg

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