Photo Credit: AI

The following is a summary of “Identification of Shared Pathways and Molecules Between Type 2 Diabetes and Lung Adenocarcinoma and the Impact of High Glucose Environment on Lung Adenocarcinoma,” published in the February 2025 issue of International Journal of Endocrinology by Yang et al. 

Researchers conducted a retrospective study to investigate the shared pathophysiological mechanisms between lung adenocarcinoma (LUAD) and Type 2 diabetes mellitus (T2DM). 

They analyzed molecular similarities between LUAD and Type 2 diabetes mellitus (T2DM) using the Gene Expression Omnibus database. Differentially expressed genes were identified, and pathway enrichment analyses were performed to determine shared molecular pathways. The GeneMANIA was used to construct a protein interaction network, highlighting STK26 as a key gene. The impact of STK26 on the tumor immune environment was evaluated using the Microenvironment Cell Populations–counter to measure stromal and immune cell levels in cancer tissues. A lung cancer cell model enriched in glucose was developed, and STK26 knockdown was achieved using small interfering RNA. The effects of STK26 on A549 cell function were estimated through cell CCK-8, wound healing (scratch), and colony formation (cloning) assays. 

The results showed that transforming growth factor-beta (TGF-β), HIF-1, AGE–RAGE, extracellular matrix (ECM) regulation, and cell adhesion pathways were activated in LUAD and T2DM. The STK26 was identified as a key gene with high expression in LUAD, correlating with poor prognosis and increased glycolysis-related pathways. Gene set variation analysis linked high STK26 levels to glycolysis, hypoxia, MYC, oxidative phosphorylation, and the cell cycle. Microenvironment Cell Populations–counter analysis indicated reduced immune infiltration in patients with high STK26 expression. Laboratory experiments confirmed that STK26 was highly expressed in LUAD cells in a high-glucose environment, and its knockdown using small interfering RNA significantly reduced cell growth and migration. 

Investigators concluded that a shared pathogenic basis exists between LUAD and T2DM, with STK26 influencing both conditions via glucose metabolism regulation, and its suppression inhibiting LUAD cell growth in high-glucose environments. 

Source: onlinelibrary.wiley.com/doi/full/10.1155/ije/7734237