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钾离子通道四聚化结构域包含蛋白 12 基因在人类癌症中的泛癌分析。

A pan-cancer analysis of potassium channel tetramerization domain containing 12 in human cancer.

机构信息

Department of Hepato-Biliary-Pancreatic Surgery, Zhengzhou University People's Hospital (Henan Provincial People's Hospital), No. 7 Weiwu Road, Jinshui District, Zhengzhou, 450000, China.

Henan University of Chinese Medicine, Zhengzhou, 450000, China.

出版信息

Sci Rep. 2023 Aug 25;13(1):13898. doi: 10.1038/s41598-023-41091-8.

DOI:10.1038/s41598-023-41091-8
PMID:37626178
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10457314/
Abstract

Abnormal expression of the potassium channel tetramerization domain containing 12 (KCTD12) is closely related to the occurrence and development of various tumors, but a pan-cancer analysis of KCTD12 has not yet been conducted. We explored the association between KCTD12 and more than 30 human malignancies using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. First, the mRNA and protein levels of KCTD12 were examined and their correlations with tumor stage and survival were explored. Second, we analyzed the infiltration of CD8 and CD4 T cells and cancer-associated fibroblasts in tumors and explored the correlation between KCTD12 expression and tumor cell stemness, genomic heterogeneity, and diagnostic specificity. Finally, we explored the molecular mechanisms associated with KCTD12 using KEGG/GO analysis. The results showed that KCTD12 mRNA and protein expression levels decreased in most tumors was significantly associated with the prognosis of tumor patients, and the phosphorylation level of KCTD12 decreased in several tumors, such as S200 and T196, pancreatic adenocarcinoma (PAAD), lung adenocarcinoma (LUAD), and breast invasive cancer (BRCA). The expression of KCTD12 was positively correlated with the degree of cancer-associated fibroblasts infiltration in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), head and neck squamous cell carcinoma (HNSC), PAAD, and stomach adenocarcinoma (STAD). The relationship between KCTD12 expression and CD8 and CD4 T cell infiltration was also clarified. KCTD12 showed high diagnostic sensitivity for various types of tumors and may be involved in tumor cell biology by affecting tumor cell stemness, tumor burden, and other characteristics. Finally, we analyzed the molecular functions of KCTD12 and possible KEGG/GO signaling pathways. In this study, we developed a biological marker for diagnosis, prognosis, and immune infiltration of the pan-cancers.

摘要

钾通道四聚化结构域包含蛋白 12(KCTD12)的异常表达与多种肿瘤的发生发展密切相关,但尚未对 KCTD12 进行泛癌分析。我们使用癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)数据库探讨了 KCTD12 与 30 多种人类恶性肿瘤之间的关联。首先,检测了 KCTD12 的 mRNA 和蛋白水平,并探讨了它们与肿瘤分期和生存的相关性。其次,我们分析了肿瘤中 CD8 和 CD4 T 细胞和癌症相关成纤维细胞的浸润情况,并探讨了 KCTD12 表达与肿瘤细胞干性、基因组异质性和诊断特异性的相关性。最后,我们使用 KEGG/GO 分析探讨了与 KCTD12 相关的分子机制。结果表明,KCTD12 的 mRNA 和蛋白表达水平在大多数肿瘤中降低与肿瘤患者的预后显著相关,并且在胰腺腺癌(PAAD)、肺腺癌(LUAD)和乳腺癌浸润性癌(BRCA)等几种肿瘤中,KCTD12 的磷酸化水平降低。KCTD12 的表达与宫颈鳞状细胞癌和子宫内膜腺癌(CESC)、头颈部鳞状细胞癌(HNSC)、PAAD 和胃腺癌(STAD)中癌症相关成纤维细胞浸润程度呈正相关。还阐明了 KCTD12 表达与 CD8 和 CD4 T 细胞浸润之间的关系。KCTD12 对各种类型的肿瘤具有较高的诊断敏感性,可能通过影响肿瘤细胞干性、肿瘤负担和其他特征来参与肿瘤细胞生物学。最后,我们分析了 KCTD12 的分子功能和可能的 KEGG/GO 信号通路。在这项研究中,我们为泛癌的诊断、预后和免疫浸润开发了一个生物标志物。

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