Cross-platform comparison of diabetic foot ulcer transcriptomes identifies partially concordant disease-associated signals

The extent to which diabetic foot ulcer transcriptomic findings agree across cohorts remains uncertain. We compared an RNA sequencing cohort of 13 ulcer and eight diabetic foot skin samples with a microarray cohort of six ulcer and three diabetic foot skin samples. Single-cell data from 26 participants were analyzed after aggregating gene counts within each patient and cell type. A further cohort of 10 ulcer and 11 healthy foot-skin samples provided a descriptive directional comparison. Healing-status comparisons were exploratory. The primary analysis selected 4,704 differentially expressed gene identifiers; 2,943 were represented among the 17,502 gene symbols shared with the microarray cohort. Of these, 1,254 had concordant directions and nominal microarray P < 0.05, including 1,028 with microarray false discovery rate < 0.05. Direction agreement was 70.2%, and overall effect-rank correlation was modest (Spearman ρ = 0.29). Five Hallmark gene sets met the cross-cohort enrichment criteria. More specific functional analysis of the stricter supported set highlighted cornified-envelope formation, keratinization and inflammatory-cell migration. In the additional cohort, 611 of 823 represented genes from this set agreed in direction, although its comparator differed. Twelve keratinocyte genes met the cell-type differential-expression threshold; this finding does not establish cell-type exclusivity. Healing-status results were sensitive to covariate adjustment. These data support partial concordance in ulcer-associated epithelial, inflammatory and metabolic expression patterns. Limited cohort coverage, comparator differences and unresolved confounding preclude a universal disease signature, healing predictor or causal interpretation.