■结核病(TB)导致肺癌(LC)的风险增加。然而,结核病的致癌机制尚不清楚。我们构建了基因共表达网络,并进行了全外显子组测序(WES)以确定关键模块,集线器基因,以及与TB相关LC发病机制相关的最频繁突变的基因。
■本研究中使用的数据从基因表达综合(GEO)和WES获得。首先,我们通过加权基因共表达网络分析(WGCNA)筛选了GSE43458中的LC相关基因和GSE83456中的TB相关基因。随后,我们在GSE42834中筛选了与LC和TB相关的差异表达基因。我们还对15名患者进行了WES(TB,n=5;LC,n=5;TB+LC,n=5),构建的突变谱,并确定了三组资料的差异,以便进一步调查。
■我们确定了278个与肺结核肿瘤发生相关的hub基因。此外,WES在15名患者的25个基因中鉴定出112个体细胞突变。最后,四个常见基因(EGFR,在278个hub基因和来自WES的突变基因的维恩图中证实了HSPA2,CECR2和LAMA3)。KEGG分析揭示了各种途径的变化。PI3K-AKT信号通路是最富集的通路,所有四个基因都包含在这个途径中。因此,这四个基因和PI3K-AKT信号通路可能在LC中起重要作用。
■确定了与结核病相关的LC相关的几个潜在基因和途径,包括EGFR和以前研究中未发现的三个靶基因。这些基因与细胞增殖有关,菌落形成,迁移,和入侵,为今后研究LC与TB共发机制提供了方向。PI3K-AKT信号通路也被确定为参与LC发展的潜在关键通路。
UNASSIGNED: Tuberculosis (TB) leads to an increased risk of lung cancer (LC). However, the carcinogenetic mechanism of TB remains unclear. We constructed gene co-expression networks and carried out whole-exome sequencing (WES) to identify key modules, hub genes, and the most recurrently mutated genes involved in the pathogenesis of TB-associated LC.
UNASSIGNED: The data used in this study were obtained from the Gene Expression Omnibus (GEO) and WES. First, we screened LC-related genes in GSE43458 and TB-related genes in GSE83456 by weighted gene co-expression network analysis (WGCNA). Subsequently, we screened differentially expressed genes related to LC and TB in GSE42834. We also performed WES of 15 patients (TB, n = 5; LC, n = 5; TB+LC, n = 5), constructed mutational profiles, and identified differences in the profiles of the three groups for further investigation.
UNASSIGNED: We identified 278 hub genes associated with tumorigenesis of pulmonary TB. Moreover, WES identified 112 somatic mutations in 25 genes in the 15 patients. Finally, four common genes (EGFR, HSPA2, CECR2, and LAMA3) were confirmed in a Venn diagram of the 278 hub genes and the mutated genes from WES. KEGG analysis revealed various pathway changes. The PI3K-AKT signaling pathway was the most enriched pathway, and all four genes are included in this pathway. Thus, these four genes and the PI3K-AKT signaling pathway may play important roles in LC.
UNASSIGNED: Several potential genes and pathways related to TB-associated LC were identified, including EGFR and three target genes not found in previous studies. These genes are related to cell proliferation, colony formation, migration, and invasion, and provide a direction for future research into the mechanisms of LC co-occurring with TB. The PI3K-AKT signaling pathway was also identified as a potential key pathway involved in LC development.