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评估LRRCl5作为胶质母细胞瘤预后和治疗生物标志物的作用。

Assessing the role of LRRCl5 as a prognostic and therapeutic biomarker in glioblastoma.

作者信息

Wan Zhixian, Wang Wenlai, Peng Shiqi, Zhao Xin

机构信息

Department of Neurosurgery, Yiling People's Hospital of Yichang City Yichang 443000, Hubei, China.

Department of Neurosurgery, Linyi People's Hospital Linyi 276000, Shandong, China.

出版信息

Am J Transl Res. 2025 Aug 15;17(8):6522-6541. doi: 10.62347/WKTK8811. eCollection 2025.

Abstract

OBJECTIVES

Glioblastoma (GBM) is the most aggressive primary brain tumor, characterized by rapid progression and poor prognosis. Identifying novel biomarkers and therapeutic targets is crucial for improving GBM outcomes. This study aimed to explore the expression, prognostic value, therapeutic significance, and functional role of Leucine-Rich Repeat Containing 15 (LRRC15) in GBM.

METHODS

We utilized data from multiple online databases to analyze LRRC15 expression and its prognostic significance. Mutational and methylation profiles were examined, followed by survival analyses. Experimental validation was conducted using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting in GBM cell lines. Functional assays, including colony formation, proliferation, and wound healing, were used to assess the effects of LRRC15 knockdown.

RESULTS

LRRC15 expression was significantly elevated in GBM. High LRRC15 levels were associated with shorter overall survival (OS) and disease-free survival (DFS) in GBM patients. Methylation analysis indicated that promoter hypermethylation may regulate LRRC15 expression. Knockdown of LRRC15 in GBM cell lines led to reduced cell proliferation, colony formation, and migration, along with a reversal of epithelial-mesenchymal transition (EMT), characterized by decreased N-cadherin and vimentin and increased E-cadherin expression.

CONCLUSION

LRRC15 is highly expressed in GBM and correlates with poor patient prognosis. Its role in enhancing cell proliferation, migration, and EMT suggests that LRRC15 contributes to GBM aggressiveness. These findings highlight LRRC15 as a promising biomarker and potential therapeutic target for GBM, warranting further investigation into LRRC15-targeted therapies.

摘要

目的

胶质母细胞瘤(GBM)是最具侵袭性的原发性脑肿瘤,其特征为进展迅速且预后不良。识别新的生物标志物和治疗靶点对于改善GBM的治疗效果至关重要。本研究旨在探讨富含亮氨酸重复序列15(LRRC15)在GBM中的表达、预后价值、治疗意义及功能作用。

方法

我们利用多个在线数据库的数据来分析LRRC15的表达及其预后意义。检测了突变和甲基化谱,随后进行生存分析。在GBM细胞系中使用逆转录定量聚合酶链反应(RT-qPCR)和蛋白质免疫印迹法进行实验验证。采用集落形成、增殖和伤口愈合等功能试验来评估LRRC15敲低的效果。

结果

LRRC15在GBM中的表达显著升高。GBM患者中LRRC15水平高与总生存期(OS)和无病生存期(DFS)较短相关。甲基化分析表明启动子高甲基化可能调节LRRC15的表达。在GBM细胞系中敲低LRRC15导致细胞增殖、集落形成和迁移减少,同时上皮-间质转化(EMT)逆转,其特征为N-钙黏蛋白和波形蛋白减少,E-钙黏蛋白表达增加。

结论

LRRC15在GBM中高表达且与患者预后不良相关。其在增强细胞增殖、迁移和EMT中的作用表明LRRC15促成了GBM的侵袭性。这些发现突出了LRRC15作为GBM有前景的生物标志物和潜在治疗靶点的地位,值得对以LRRC15为靶点的治疗进行进一步研究。

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