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脑胶质瘤中纤毛相关基因特征的临床和分子分析及其对预后预测的价值。

Clinical and molecular analysis of cilia-associated gene signature for prognostic prediction in glioma.

机构信息

Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, China.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Research Unit of Oral Carcinogenesis and Management, Chinese Academy of Medical Sciences, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

出版信息

J Cancer Res Clin Oncol. 2023 Oct;149(13):11443-11455. doi: 10.1007/s00432-023-05022-4. Epub 2023 Jun 30.

Abstract

PURPOSE

Glioma is a highly malignant and unfavorable cancer in the brain. Recent evidence highlights the vital role of cilia-related pathways as novel regulators of glioma development. However, the prognostic potential of ciliary pathways in glioma is still ambiguous. In this study, we aim to construct a gene signature using cilia-related genes to facilitate the prognostication of glioma.

METHODS

A multi-stage approach was employed to build the ciliary gene signature for prognostication of glioma. The strategy involved the implementation of univariate, LASSO, and stepwise multivariate Cox regression analyses based on TCGA cohort, followed by independent validation in CGGA and REMBRANDT cohort. The study further revealed molecular differences at the genomic, transcriptomic, and proteomic levels between distinct groups.

RESULTS

A prognostic tool utilizing a 9-gene signature based on ciliary pathways was developed to assess the clinical outcomes of glioma patients. The risk scores generated by the signature demonstrated a negative correlation with patient survival rates. The validation of the signature in an independent cohort reinforced its prognostic capabilities. In-depth analysis uncovered distinctive molecular characteristics at the genomic, transcriptomic, and protein-interactive levels in the high- and low-risk groups. Furthermore, the gene signature was able to predict the sensitivity of glioma patients to conventional chemotherapeutic drugs.

CONCLUSION

This study has established the utility of a ciliary gene signature as a reliable prognostic predictor of glioma patient survival. Findings not only enhance our comprehension of the intricate molecular mechanisms of cilia pathways in glioma, but also hold significant clinical implications in directing chemotherapeutic strategies.

摘要

目的

脑胶质瘤是一种高度恶性和预后不良的脑肿瘤。最近的证据强调了纤毛相关途径作为胶质瘤发生的新型调节因子的重要作用。然而,纤毛通路在胶质瘤中的预后潜力仍然存在争议。在这项研究中,我们旨在构建一个使用纤毛相关基因的基因特征,以促进胶质瘤的预后。

方法

采用多阶段方法构建用于预测胶质瘤的纤毛基因特征。该策略包括基于 TCGA 队列进行单变量、LASSO 和逐步多变量 Cox 回归分析,然后在 CGGA 和 REMBRANDT 队列中进行独立验证。该研究进一步揭示了不同组之间在基因组、转录组和蛋白质组水平上的分子差异。

结果

开发了一种基于纤毛通路的 9 个基因的预后工具,用于评估胶质瘤患者的临床结局。该特征产生的风险评分与患者生存率呈负相关。在独立队列中的验证加强了其预后能力。深入分析揭示了高风险和低风险组在基因组、转录组和蛋白质相互作用水平上的独特分子特征。此外,该基因特征能够预测胶质瘤患者对常规化疗药物的敏感性。

结论

本研究证实了纤毛基因特征作为胶质瘤患者生存的可靠预后预测因子的实用性。研究结果不仅增强了我们对纤毛通路在胶质瘤中复杂分子机制的理解,而且对指导化疗策略具有重要的临床意义。

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