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鉴定一种创新的分类和列线图,用于预测甲状腺癌患者的预后,并提供治疗方案。

Identification an innovative classification and nomogram for predicting the prognosis of thyroid carcinoma patients and providing therapeutic schedules.

机构信息

Department of Endocrinology, Shuyang County Hospital of Traditional Chinese Medicine, Jiangsu, 223600, China.

出版信息

J Cancer Res Clin Oncol. 2023 Nov;149(16):14817-14831. doi: 10.1007/s00432-023-05252-6. Epub 2023 Aug 18.

Abstract

BACKGROUND

Thyroid carcinoma (THCA) represents a prevalent form of cancer globally, with its incidence demonstrating an upward trend in recent years. Accumulating evidence has indicated that programmed cell death (PCD) patterns exert a vital influence on tumor progression. Nevertheless, the association between PCD and the prognosis of patients with papillary thyroid carcinoma remains to be elucidated. The current study endeavors to examine the link between PCD and the prognosis of thyroid cancer while concurrently developing a prognostic index based on PCD genes.

MATERIALS AND METHODS

Programmed cell death patterns were employed to construct the model and define clusters. Gene expression profile genomics and clinical data pertaining to 568 patients with thyroid cancer were sourced from the TCGA database. In addition, single-cell transcriptome data GSE184362 were procured from the Gene Expression Omnibus (GEO) database for subsequent analysis.

RESULTS

The study harnessed six machine learning algorithms to create a programmed cell death signature (PCDS). Ultimately, the model developed via SVM was chosen as the optimal model, boasting the highest C-index. Moreover, the application of non-negative matrix factorization (NMF) led to the identification of two molecular subtypes of THCA, each characterized by distinct vital biological processes and drug sensitivities. The investigation revealed that PCDS is linked to chemokines, interleukins, interferons, and checkpoint genes, as well as pivotal components of the tumor microenvironment, as determined through a comprehensive analysis of bulk and single-cell transcriptomes. Patients with THCA and elevated PCDS values are more inclined to exhibit resistance to conventional chemotherapy regimens, yet may display heightened responsiveness to targeted therapeutic agents. Finally, we established a nomogram model based on multivariable cox and logistic regression analyses to predict the overall survival of THCA patients.

CONCLUSION

This research sheds new light on the role of programmed cell death (PCD) patterns in THCA. By conducting an in-depth analysis of various cell death patterns, a novel PCD model has been devised, capable of accurately predicting the clinical prognosis and drug sensitivity of patients with THCA.

摘要

背景

甲状腺癌(THCA)是一种全球普遍存在的癌症,近年来其发病率呈上升趋势。越来越多的证据表明,细胞程序性死亡(PCD)模式对肿瘤的进展起着至关重要的影响。然而,PCD 与甲状腺乳头状癌患者的预后之间的关联仍需阐明。本研究旨在探讨 PCD 与甲状腺癌预后之间的关系,并基于 PCD 基因构建预后指数。

材料和方法

采用细胞程序性死亡模式构建模型并定义聚类。从 TCGA 数据库中获取 568 例甲状腺癌患者的基因表达谱基因组学和临床数据。此外,从基因表达综合数据库(GEO)中获取单细胞转录组数据 GSE184362 进行后续分析。

结果

本研究利用六种机器学习算法构建了细胞程序性死亡特征(PCDS)。最终,选择 SVM 开发的模型作为最优模型,具有最高的 C 指数。此外,应用非负矩阵分解(NMF)可识别两种 THCA 分子亚型,每种亚型都具有独特的重要生物学过程和药物敏感性。通过对批量和单细胞转录组的全面分析,发现 PCDS 与趋化因子、白细胞介素、干扰素和检查点基因以及肿瘤微环境的关键组成部分有关。具有高 PCDS 值的 THCA 患者更倾向于对常规化疗方案产生耐药性,但可能对靶向治疗药物更敏感。最后,我们基于多变量 cox 和逻辑回归分析建立了一个预测 THCA 患者总体生存率的列线图模型。

结论

本研究揭示了细胞程序性死亡(PCD)模式在 THCA 中的作用。通过深入分析各种细胞死亡模式,构建了一种新的 PCD 模型,能够准确预测 THCA 患者的临床预后和药物敏感性。

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