Weighted gene co-expression network analysis and whole genome sequencing identify potential lung cancer biomarkers

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.