Epidemiological and transcriptome data identify shared gene signatures and immune cell infiltration in type 2 diabetes and non-small cell lung cancer

Abstract

Background: Numerous previous studies have reported an association between type 2 diabetes mellitus (T2DM) and lung cancer risk, but the underlying mechanism of the interaction remains unclear. This study aimed to investigate the shared genetic features and immune infiltration processes between lung cancer and T2DM. Methods: Epidemiological data from the National Health and Nutrition Examination Survey (NHANES) 2000–2018 was used to explore the relationship between lung cancer and diabetes systematically. In addition, we also used bioinformatics methods to analyze the transcriptome data from the Gene Expression Omnibus (GEO) to explore the potential functional mechanisms from the perspective of genes and immune infiltration. Results: Logistic regression analysis showed that prediabetes (OR = 3.289,95%CI 1.231, 8.788, p = 0.01760, model 3)and type 2 diabetes (OR = 3.032 95%CI,1.015, 9.054, p = 0.04689) were significantly associated with an increased risk of lung cancer after adjusting for multiple covariates. Data from NHANES showed an inverted U-shaped relationship between fasting blood glucose and glycosylated haemoglobin and the risk of lung cancer (P for non-linear < 0.001). Transcriptome data showed that we screened 57 co-DEGs, of which 25 were up-regulated co-DEGs and 32 were down-regulated. Ten core DEGs were identified by bioinformatics analysis, which were SMC6, CDC27, CDC7, RACGAP1, SMC4, NCF4, NCF1, NCF2, SELPLG and CFP. Correlation analysis showed that some core DEGs were significantly associated with simultaneous dysregulation of immune cells. Conclusion: The identified core genes of NSCLC and T2DM are associated with dysregulated immune cells, which provides a potential research avenue for diagnosing and treating lung cancer combined with diabetes.