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

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.