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基于转录组学的铜死亡相关基因特征作为甲状腺癌的预后生物标志物

A Cuproptosis-Related gene Signature as a Prognostic Biomarker in Thyroid Cancer Based on Transcriptomics.

作者信息

Guan Zirui, Wang Hongyong, Tian Mingyan

机构信息

The Second Hospital of Jilin University, Changchun City, 130022, Jilin Province, People's Republic of China.

出版信息

Biochem Genet. 2025 Apr;63(2):1584-1604. doi: 10.1007/s10528-024-10767-9. Epub 2024 Apr 9.

Abstract

Thyroid cancer (THCA) is the most prevalent endocrine tumor, and its incidence continues to increase every year. However, the processes underlying the aggressive progression of thyroid cancer are unknown. We concentrated on the prognostic and biological importance of thyroid cancer cuproptosis-related genes in this investigation. Genomic and clinical data were obtained from the UCSC XENA website, and cuproptosis-related genes were obtained from the FerrDb website. We performed differential expression analysis and Cox regression analysis to identify possible predictive targets associated with thyroid cancer prognosis. To assess the role of CDKN2A in thyroid cancer and the ability to predict prognosis on the basis of the CDKN2A expression level, we performed immunohistochemical staining, survival analysis, immunological analysis, functional analysis, and clinical analysis with respect to CDKN2A gene expression. CDKN2A expression levels were found to be inversely correlated with thyroid cancer prognosis. Higher levels of CDKN2A expression were associated with higher T, N, and clinicopathological stage and more residual tumor cells. Through univariate and multivariate Cox regression analyses, the CDKN2A expression level was shown to be linked with thyroid cancer patients' overall survival (OS). Moreover, we discovered that CDKN2A expression was linked to a dysfunctional tumor immune microenvironment. The study shows that CDKN2A, a cuproptosis-related gene, can be used as a prognostic marker for thyroid cancer.

摘要

甲状腺癌(THCA)是最常见的内分泌肿瘤,其发病率每年都在持续上升。然而,甲状腺癌侵袭性进展的潜在机制尚不清楚。在本研究中,我们聚焦于甲状腺癌铜死亡相关基因的预后及生物学重要性。基因组和临床数据来自UCSC XENA网站,铜死亡相关基因来自FerrDb网站。我们进行了差异表达分析和Cox回归分析,以确定与甲状腺癌预后相关的潜在预测靶点。为了评估CDKN2A在甲状腺癌中的作用以及基于CDKN2A表达水平预测预后的能力,我们针对CDKN2A基因表达进行了免疫组织化学染色、生存分析、免疫分析、功能分析和临床分析。结果发现,CDKN2A表达水平与甲状腺癌预后呈负相关。较高水平的CDKN2A表达与更高的T、N分期及临床病理分期以及更多的残留肿瘤细胞相关。通过单因素和多因素Cox回归分析,CDKN2A表达水平与甲状腺癌患者的总生存期(OS)相关。此外,我们发现CDKN2A表达与功能失调的肿瘤免疫微环境有关。该研究表明,铜死亡相关基因CDKN2A可作为甲状腺癌的预后标志物。

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