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肺腺癌中与缺氧微环境和免疫浸润相关的 KCTD 家族基因的综合分析

英文原题:Comprehensive analysis of KCTD family genes associated with hypoxic microenvironment and immune infiltration in lung adenocarcinoma.

查看英文原题

Comprehensive analysis of KCTD family genes associated with hypoxic microenvironment and immune infiltration in lung adenocarcinoma.

PubMed 2022/06/15(内容时间) Sci Rep Q1 · IF 4.9(JCR 2025)

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中文摘要

为了获得对LUAD肿瘤生物学和治疗靶点的新见解,我们对KCTD家族基因进行了全面分析。通过多种生物信息学挖掘,确定了KCTD家族的表达模式和临床意义。

此外,利用TIMER 2.0、cBioPortal、GeneMANIA、LinkedOmics和GSEA评估了差异表达KCTD的分子功能和潜在机制。

结果表明,KCTD9、KCTD10、KCTD12、KCTD15和KCTD16的mRNA和蛋白表达水平在LUAD中显著降低,而KCTD5的表达水平显著升高。KCTD5高表达与晚期肿瘤分期、淋巴结转移、TP53突变和不良预后显著相关。

此外,KCTD5与CD8+ T细胞、中性粒细胞、巨噬细胞和树突状细胞浸润呈正相关。另外,KCTD在LUAD的诊断中展现出良好的前景。

重要的是,KCTD5高表达富集于与肿瘤恶性进展相关的信号通路,包括炎症反应、IL6/JAK/STAT3信号通路、EMT和缺氧。

进一步的关联分析显示,KCTD5与HIF1等缺氧相关基因呈正相关。总体而言,KCTD可作为LUAD治疗的分子靶点,以及用于诊断和预后预测的有效分子生物标志物。

展开英文摘要原文

To obtain novel insights into the tumor biology and therapeutic targets of LUAD, we performed a comprehensive analysis of the KCTD family genes. The expression patterns and clinical significance of the KCTD family were identified through multiple bioinformatics mining.

Moreover, the molecular functions and potential mechanisms of differentially expressed KCTDs were evaluated using TIMER 2. 0, cBioPortal, GeneMANIA, LinkedOmics and GSEA. The results indicated that the mRNA and protein expression levels of KCTD9, KCTD10, KCTD12, KCTD15 and KCTD16 were significantly decreased in LUAD, while those of KCTD5 were significantly increased. High KCTD5 expression was significantly associated with advanced tumor stage, lymph node metastasis, TP53 mutation and poor prognosis.

In addition, KCTD5 was positively correlated with CD8 + T cell, neutrophil, macrophage and dendritic cell infiltration.

Additionally, KCTDs demonstrate promising prospects in the diagnosis of LUAD.

Importantly, high KCTD5 expression was enriched in signaling pathways associated with the malignant progression of tumors, including the inflammatory response, the IL6/JAK/STAT3 signaling pathway, EMT and hypoxia.

Further association analysis showed that KCTD5 was positively correlated with hypoxia-related genes such as HIF1.

Overall, KCTDs can be used as molecular targets for the treatment of LUAD, as well as effective molecular biomarkers for diagnosis and prognosis prediction.

论文信息

作者
Shi YX、Zhang WD、Dai PH、Deng J、Tan LH
第一作者单位
Institute of Clinical Medicine, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, Hunan, People's Republic of China. yuanxiangshi@hunnu.edu.cn.China
通讯作者单位
Institute of Clinical Medicine, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, Hunan, People's Republic of China. Tanlihong118@163.com.China
文献类型
非美国政府资助研究
期刊
Scientific reports2022 Jun 15
原文标识
PubMed 35705627 · DOI 10.1038/s41598-022-14250-6