Fig. 3: Proteomic differences of common SCCs and rare SCCs.

a Principal-component analysis (PCA) of common SCCs and rare SCCs. b The association of common and rare SCCs with 9 variables (two-sided Fisher’s exact test was used for categorical variables and two-sided Wilcoxon rank-sum test was used for continuous variables), and the heatmap of significantly DEPs (Wilcoxon rank-sum test, BH-adjusted p < 0.05, fold change > 2) in common SCCs and rare SCCs. c Enriched pathways of significantly DEPs (two-sided Wilcoxon rank-sum test, BH-adjusted p < 0.05, fold change > 2) in common SCCs and rare SCCs. d Proteins in pathways that were differentially expressed in common SCCs and rare SCCs, and representative DEPs. e The PLIN1 protein expression in 17 SCCs. f Representative PLIN1 fluorescence in situ hybridization signal patterns (red signals = PLIN1, green signals = CEP15), left, this case (Anus_3) was scored negative for PLIN1 amplification. PLIN1/nucleus ratio = 2.52; right, this case (Anus_10) was scored as positive for PLIN1 amplification. PLIN1/nucleus ratio = 6.2. The boxes indicate the interquartile ranges, and no outliers are shown. g Differential expressed TFs (two-sided Wilcoxon rank-sum test, BH-adjusted p < 0.05, fold change > 2) in common SCCs and rare SCCs. The two TFs, RUNX2 and FOXO1, were labeled in blue. h The expression heatmap of downstream transcriptional targeted genes (TGs) regulated by RUNX2 and FOXO1 (in bold). The expression level was scaled by row. i A scatterplot showed the association between the protein abundance of RUNX2 (x-axis) and FOXO1 (y-axis). Pairwise Spearman correlation. j Immunohistochemistry staining for RUNX2, FOXO1, and PLIN1 expression in rare SCCs (one case of thyroid SCC and one case of pancreatic SCC) was concordant with the mass spectrometry findings. Scale bar, 100 μm. k Diagram depicted our hypothesis of lipid metabolism upregulation contributing to rare SCC aggressiveness and metastasis. Source data are provided as a Source Data file.