Transcriptomic analysis of MCEMP1 and CLEC4D as candidate biomarkers for type 2 diabetes complicated with ischemic stroke

Type 2 diabetes mellitus (T2DM) is a major risk factor for ischemic stroke (IS), yet their shared molecular mechanisms are not fully understood. This study aimed to identify key genes linking T2DM and IS to provide insights into comorbid pathogenesis. In the discovery phase, we adopted public transcriptomic datasets containing patients with simple T2DM or simple IS (no comorbid patients included), and screened common differentially expressed genes from the two independent single-disease cohorts to explore shared molecular alterations between the two disorders. Through integrative bioinformatics analysis of public transcriptomic data, we identified candidate genes and further pinpointed MCEMP1 and CLEC4D as central hub genes. A diagnostic nomogram based on these genes showed good predictive performance. Functional enrichment analysis revealed their association with critical pathways like the JAK-STAT signaling pathway and immune dysregulation. Transcriptional regulatory network and drug prediction analyses were also conducted. Subsequent reverse transcription quantitative PCR (RT-qPCR) validation was performed using clinical samples from patients with T2DM complicated by IS. The significant overexpression of MCEMP1 and CLEC4D in clinical samples from T2DM and IS patients was validated by RT-qPCR. In conclusion, MCEMP1 and CLEC4D are identified as key genes at the T2DM-IS interface, representing previously unrecognized shared molecular mediators between the two diseases and offering potential diagnostic biomarkers and therapeutic targets for this comorbidity.