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综合生物信息学方法揭示 LRP1 表达在卵巢癌中的预后意义。

The Integrated Bioinformatic Approach Reveals the Prognostic Significance of LRP1 Expression in Ovarian Cancer.

机构信息

Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China.

Tsinghua Berkeley Shenzhen Institute, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China.

出版信息

Int J Mol Sci. 2024 Jul 22;25(14):7996. doi: 10.3390/ijms25147996.

Abstract

A hyperactive tumour microenvironment (TME) drives unrestricted cancer cell survival, drug resistance, and metastasis in ovarian carcinoma (OC). However, therapeutic targets within the TME for OC remain elusive, and efficient methods to quantify TME activity are still limited. Herein, we employed an integrated bioinformatics approach to determine which immune-related genes (IRGs) modulate the TME and further assess their potential theragnostic (therapeutic + diagnostic) significance in OC progression. Using a robust approach, we developed a predictive risk model to retrospectively examine the clinicopathological parameters of OC patients from The Cancer Genome Atlas (TCGA) database. The validity of the prognostic model was confirmed with data from the International Cancer Genome Consortium (ICGC) cohort. Our approach identified nine IRGs, , , , , , , , , and , that form a prognostic model in OC progression, distinguishing patients with significantly better clinical outcomes in the low-risk group. We validated this model as an independent prognostic indicator and demonstrated enhanced prognostic significance when used alongside clinical nomograms for accurate prediction. Elevated expression, which indicates poor prognosis in bladder cancer (BLCA), OC, low-grade gliomas (LGG), and glioblastoma (GBM), was also associated with immune infiltration in several other cancers. Significant correlations with immune checkpoint genes (ICGs) highlight the potential importance of LRP1 as a biomarker and therapeutic target. Furthermore, gene set enrichment analysis highlighted LRP1's involvement in metabolism-related pathways, supporting its prognostic and therapeutic relevance also in BLCA, OC, low-grade gliomas (LGG), GBM, kidney cancer, OC, BLCA, kidney renal clear cell carcinoma (KIRC), stomach adenocarcinoma (STAD), and stomach and oesophageal carcinoma (STES). Our study has generated a novel signature of nine IRGs within the TME across cancers, that could serve as potential prognostic predictors and provide a valuable resource to improve the prognosis of OC.

摘要

一个过度活跃的肿瘤微环境(TME)驱动卵巢癌(OC)中不受限制的癌细胞存活、耐药性和转移。然而,OC 中 TME 的治疗靶点仍然难以捉摸,并且量化 TME 活性的有效方法仍然有限。在此,我们采用综合的生物信息学方法来确定哪些免疫相关基因(IRGs)调节 TME,并进一步评估它们在 OC 进展中的潜在治疗和诊断意义。我们使用一种稳健的方法,开发了一个预测风险模型,用于回顾性检查来自癌症基因组图谱(TCGA)数据库的 OC 患者的临床病理参数。该预后模型的有效性通过国际癌症基因组联盟(ICGC)队列的数据得到了验证。我们的方法确定了九个 IRGs, , , , , , , 和 ,它们在 OC 进展中形成一个预后模型,将低风险组中具有明显更好临床结果的患者区分开来。我们验证了该模型作为独立的预后指标,并证明当与临床列线图一起用于准确预测时,具有增强的预后意义。在膀胱癌(BLCA)、OC、低级别胶质瘤(LGG)和胶质母细胞瘤(GBM)中,表达升高表明预后不良,与其他几种癌症中的免疫浸润也相关。与免疫检查点基因(ICGs)的显著相关性突出了 LRP1 作为生物标志物和治疗靶点的潜在重要性。此外,基因集富集分析强调了 LRP1 参与代谢相关途径,支持其在 BLCA、OC、低级别胶质瘤(LGG)、GBM、肾癌、OC、BLCA、肾透明细胞癌(KIRC)、胃腺癌(STAD)和胃食管癌(STES)中的预后和治疗相关性。我们的研究在跨癌症的 TME 中生成了一个新的九个 IRG 特征,它可以作为潜在的预后预测因子,并为改善 OC 的预后提供有价值的资源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9942/11276689/d5d16e21a9ce/ijms-25-07996-g001.jpg

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