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新型抗肿瘤免疫干扰因子GDF-15在多种癌症中的功能特性

Functional characteristics of fresh antitumor immune interferer GDF-15 in multiple cancers.

作者信息

Fang Min, Wang Ziyu, Zhou Yuxin, Yang Fengrui, Wu Zhu, Xiao Jian

机构信息

Hunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University, Changsha, 410219, China.

"The 14th Five-Year Plan" Application Characteristic Discipline of Hunan Province (Pharmaceutical Science), Changsha Medical University, Changsha, China.

出版信息

Sci Rep. 2025 Aug 22;15(1):30864. doi: 10.1038/s41598-025-16737-4.

Abstract

We designed our study with the aim of conducting a comprehensive analysis of the role that GDF-15 plays in pan-cancer. Multiple databases were used to obtain GDF-15 expression. XIANTAO Academic and Sangerbox were utilized to conduct the diagnostic significance of GDF-15 expression across pan-cancer. The relationships between GDF-15 expression and clinical data, tumor stemness, genomic instability, and tumor prognosis in pan-cancer were evaluated. The interaction between molecules and RNA methylation phenotypes related to GDF-15 were explored. The correlations between GDF-15 expression and immune cell infiltration, immune-related genes, as well as immune checkpoints were also under investigation. Besides, immunohistochemistry (IHC)-based tissue microarray analysis of LUAD validated GDF-15 protein expression and its correlation with survival prognosis. GDF-15 exhibited differential expression across various cancers, being upregulated in BRCA, CHOL, COAD, HNSC, LIHC, LUAD, READ, STAD, THCA, and UCEC, but downregulated in KIRC and LUSC. Its expression correlated with clinical parameters and GDF-15 expression had prognostic value in some cancers. Notably, it had a remarkable diagnostic value in CHOL, COAD, ESCC, GBM, LAML, READ and THCA. GDF-15 was involved in influencing tumor stemness, genomic instability. Besides, GDF-15 interacted with molecules involved in iron ion homeostasis and acute-phase response, receptor activator, ligand activities and cellular senescence. It was intertwined with key tumor processes. Moreover, GDF-15 expression further influenced immune cell infiltration, related immune genes, and immune checkpoints. More importantly, IHC staining results of tissue microarrays confirmed its differential protein expression in LUAD tissues, where elevated levels were significantly associated with poorer overall survival, underscoring its clinical relevance. GDF-15 functioned as a prospective indicator for both the diagnosis and prognosis in various cancers.

摘要

我们开展本研究的目的是全面分析生长分化因子15(GDF-15)在泛癌中的作用。使用多个数据库获取GDF-15表达数据。利用仙桃学术和生信盒子分析GDF-15表达在泛癌中的诊断意义。评估GDF-15表达与泛癌临床数据、肿瘤干性、基因组不稳定性及肿瘤预后之间的关系。探索与GDF-15相关的分子与RNA甲基化表型之间的相互作用。还研究了GDF-15表达与免疫细胞浸润、免疫相关基因以及免疫检查点之间的相关性。此外,基于免疫组织化学(IHC)的肺腺癌组织芯片分析验证了GDF-15蛋白表达及其与生存预后的相关性。GDF-15在各种癌症中表现出差异表达,在乳腺癌、胆管癌、结肠癌、头颈部鳞状细胞癌、肝癌、肺腺癌、直肠癌、胃癌、甲状腺癌和子宫内膜癌中上调,但在肾透明细胞癌和肺鳞癌中下调。其表达与临床参数相关,并且GDF-15表达在某些癌症中具有预后价值。值得注意的是,它在胆管癌、结肠癌、食管癌、胶质母细胞瘤、急性髓系白血病、直肠癌和甲状腺癌中具有显著的诊断价值。GDF-15参与影响肿瘤干性、基因组不稳定性。此外GDF-15与参与铁离子稳态和急性期反应、受体激活剂、配体活性及细胞衰老的分子相互作用。它与关键的肿瘤过程相互交织。此外,GDF-15表达进一步影响免疫细胞浸润、相关免疫基因和免疫检查点。更重要的是,组织芯片的IHC染色结果证实了其在肺腺癌组织中的差异蛋白表达,其中水平升高与较差的总生存期显著相关,强调了其临床相关性。GDF-15作为多种癌症诊断和预后的潜在指标发挥作用。

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