Fig. 4: Association between metagene expression and clinical symptoms or blood cytokine levels based on the cross-sectional study.

A The y-axis represents the metagene expression score, which was calculated by the sum of expression values of 12 disease-associated metagenes, namely, SKITm17, SKITm10, SKITm9, SKITm15, SKITm11, SKITm8, SKITm6, SKITm5, SKITm4, SKITm1, SKITm2 and SKITm16. All the expression values of each sample were divided by the maximum expression value in each metagene for normalization (relative expression values). The expression values for SKITm2 and SKITm16 were then subtracted from 1 before the calculation of the metagene expression score. The relative expression value was used for analysis throughout the cross-sectional and longitudinal analysis. The metagene expression score between normal samples and lesional AD and non-lesional AD were tested by Wilcoxon test. The p values were corrected using the Bonferroni method for multiple comparisons. In box plots, the center line represents the median; the lower and upper bounds of the box represent the 25th and 75th percentiles, respectively; whiskers extend to the smallest and largest values within 1.5× the interquartile range from the lower and upper quartiles. N (samples) = 49 (normal), 246 (lesional AD), and 170 (non-lesional AD). *p < 0.01. B The y-axis represents the local severity score, calculated by the sum of clinical severity scores of erythema, papulation/induration, excoriation, and lichenification of the sampled sites. n (samples) = 49 (normal), 235 (lesional AD), and 159 (non-lesional AD). *p < 0.01. C The y-axis represents the total disease severity (EASI). n (samples) = 49 (normal), 234 (lesional AD), and 156 (non-lesional AD). *p < 0.01. For (B, C), the severity scores of normal samples were set to 0. The r and p indicate the correlation coefficient and the significance obtained through Spearman’s correlation analysis, respectively. The linear regression line is shown with a gray shaded area indicating the 95% confidence interval of the fitted line. D Heatmap depicting p values obtained from a regression analysis of the severity of skin phenotypes (erythema, papulation/induration, excoriation, lichenification), the overall severity (EASI), and pruritus score. Results from PN and LA lesions were compared with those of non-lesional samples from the same patients using a paired t-test. Red and blue indicate a significant positive and negative association with metagene expression and the severity of symptoms, respectively. Statistical significance was assessed using a two-sided test. Sample sizes: erythema/papulation/excoriation/lichenification (n = 212), LA (n = 12), PN (n = 16), pruritus (lesional, n = 230; non-lesional, n = 151), EASI (lesional, n = 235; non-lesional, n = 159). E Heatmap displaying p values obtained from regression analysis of plasma/serum cytokine levels. Statistical significance of regression coefficients was assessed using a two-sided test. EDN eosinophil-derived neurotoxin, TSLP thymic stromal lymphopoietin. Sample sizes: lesional, n = 224 samples (206 for CCL17); non-lesional, n = 148 (140 for CCL17). For (D, E), no adjustments for multiple comparisons were made, as the analyses were exploratory in nature. Source data are provided as a Source Data file.