Identification of Shared Pathways and Molecules Between Type 2 Diabetes and Lung Adenocarcinoma and the Impact of High Glucose Environment on Lung Adenocarcinoma.

Objective: This research focused on exploring the shared pathophysiological bases of lung adenocarcinoma (LUAD) and Type 2 diabetes mellitus (T2DM). Methods: The investigation into the molecular similarities between LUAD and T2DM involved querying the Gene Expression Omnibus for pertinent data. Upon pinpointing genes exhibiting differential expression, pathway enrichment analyses were executed to discern the molecular pathways shared by both conditions. In addition, GeneMANIA was employed to establish a protein interaction network, pinpointing STK26 as a critical gene. In addition, the influence of STK26 on the immune environment of the tumor was examined using tools such as the Microenvironment Cell Populations-counter to assess levels of stromal and immune cells in cancer tissues from expression profiles. Furthermore, a lung cancer cell model enriched in glucose was developed to facilitate the knockdown of STK26 using small interfering RNA. The influence of STK26 on A549 cell functionality was assessed using CCK-8, wound healing (scratch), and colony formation (cloning) assays. Results: This will help ensure accuracy and relevance in the revised version. TGF-β, HIF-1, AGE-RAGE, extracellular matrix (ECM) components and function regulation, and cell adhesion were activated in LUAD and T2DM. WGCNA identified two main modules in LUAD, three main modules in T2DM, and 44 shared genes. ClueGO and GeneMANIA analyses focused on pathways regulating cell growth and mitosis. Our analysis revealed STK26 as a central gene that exhibits elevated expression levels in tissues affected by LUAD. Elevated expression of STK26 correlates with a diminished prognosis for LUAD patients. In patients with LUAD characterized by elevated STK26 levels, gene set enrichment analysis identified a notable upregulation in numerous metabolic pathways. These include glycolysis-gluconeogenesis, oxidative phosphorylation, and the conversion pathways between pentose and glucuronic acid, as well as the pentose phosphate pathway. Gene set variation analysis suggested that a high STK26 expression was related to glycolysis, hypoxia, MYC, oxidative phosphorylation, cell cycle, and citric acid cycle pathways. In the group exhibiting elevated levels of STK26, a marked upregulation of glycolytic pathway genes, including HK2, RPIA, IDH3G, and SORD, was noted. This upregulation indicates a correlation between STK26 expression and these pivotal glycolytic genes. MCP-counter analysis suggested that the group with a high STK26 expression level had reduced immune infiltration. Laboratory studies have demonstrated that LUAD cells thrive in a high-glucose setting, where STK26 expression notably surpasses that observed under standard conditions. In addition, suppressing STK26 using siRNA significantly curtails both the growth and movement of LUAD cells. Conclusion: The research established a shared pathogenic basis between LUAD and T2DM. TGF-β, HIF-1, AGE-RAGE, ECM components and function regulation, cell adhesion, and additional signaling pathways are intricately linked with the pathophysiological mechanisms underlying both LUAD and T2DM. Thus, STK26 may affect the development of LUAD and T2DM by regulating glucose metabolism. Suppressing STK26 in a glucose-rich setting curtailed both the expansion and mobility of LUAD cells.