Table 3. Gene Ontology and Reactome pathway enrichment analyses for 388 downregulated genes in post-treatment versus pre-treatment actinic keratoses that responded to ingenol mebutate gel.

	Biological Process (GO)
GO-term	Description	FDR	Downregulated matching proteins
GO:0008544	Epidermis development	2.88E-18	ANXA1, BNC1, CASP14, CDH3, CNFN, COL17A1, CRABP2, CSTA, DSC2, DSG3, EREG, FABP5, GRHL3, HDAC1, HRNR, IVL, JUP, KLK13, KRT14, KRT16, KRT17, KRT19, KRT5, KRT6A, KRT6B, KRT6C, KRT80, LAMA3, LAMB3, LCE2A, LCE3A, LCE3C, LCE3D, LCE3E, PI3, PIP5K1A, RPTN, S100A7, SFN, SPRR1A, SPRR1B, SPRR2A, SPRR2B, SPRR2D, SPRR2E, SPRR2F, SPRR2G, SPRR3
GO:0030216	Keratinocyte differentiation	2.94E-18	ANXA1, CASP14, CDH3, CNFN, CSTA, DSC2, DSG3, EREG, HRNR, IVL, JUP, KLK13, KRT14, KRT16, KRT17, KRT19, KRT5, KRT6A, KRT6B, KRT6C, KRT80, LCE2A, LCE3A, LCE3C, LCE3D, LCE3E, PI3, PIP5K1A, RPTN, S100A7, SFN, SPRR1A, SPRR1B, SPRR2A, SPRR2B, SPRR2D, SPRR2E, SPRR2F, SPRR2G, SPRR3
GO:0009913	Epidermal cell differentiation	2.32E-17	ANXA1, CASP14, CDH3, CNFN, CSTA, DSC2, DSG3, EREG, HDAC1, HRNR, IVL, JUP, KLK13, KRT14, KRT16, KRT17, KRT19, KRT5, KRT6A, KRT6B, KRT6C, KRT80, LCE2A, LCE3A, LCE3C, LCE3D, LCE3E, PI3, PIP5K1A, RPTN, S100A7, SFN, SPRR1A, SPRR1B, SPRR2A, SPRR2B, SPRR2D, SPRR2E, SPRR2F, SPRR2G, SPRR3
GO:0031424	Keratinization	2.32E-17	CASP14, CDH3, CNFN, CSTA, DSC2, DSG3, HRNR, IVL, JUP, KLK13, KRT14, KRT16, KRT17, KRT19, KRT5, KRT6A, KRT6B, KRT6C, KRT80, LCE2A, LCE3A, LCE3C, LCE3D, LCE3E, PI3, RPTN, SFN, SPRR1A, SPRR1B, SPRR2A, SPRR2B, SPRR2D, SPRR2E, SPRR2F, SPRR2G, SPRR3
GO:0070268	Cornification	2.32E-17	CASP14, CSTA, DSC2, DSG3, IVL, JUP, KLK13, KRT14, KRT16, KRT17, KRT19, KRT5, KRT6A, KRT6B, KRT6C, KRT80, LCE3D, PI3, RPTN, SPRR1A, SPRR1B, SPRR2A, SPRR2B, SPRR2D, SPRR2E, SPRR2F, SPRR2G, SPRR3
	Reactome pathways
Pathway	Description	FDR	Downregulated matching proteins
HSA-6809371	Formation of the cornified envelope	2.01E-20	CASP14, CSTA, DSC2, DSG3, IVL, JUP, KLK13, KRT14, KRT16, KRT17, KRT19, KRT5, KRT6A, KRT6B, KRT6C, KRT80, LCE2A, LCE3A, LCE3C, LCE3D, LCE3E, PI3, RPTN, SPRR1A, SPRR1B, SPRR2A, SPRR2B, SPRR2D, SPRR2E, SPRR2F, SPRR2G, SPRR3
HSA-9014826	Immune system	8.47E-08	L36RN, IL6, IL7R, JUNB, JUP, KIF18A, KIF20A, KIF23, KPNA2, LCN2, MALT1, MCL1, MMP1, MT2A, MYC, MYD88, NDC1, PGAM1, PI3, PKM, PLAC8, PLAUR, PNP, POLR3G, PRSS3, PSMA6, PSMD11, PSME3, PTGS2, PYGL, S100A12, S100A7, S100A7A, S100A8, S100A9, SEC31A, SELL, SERPINB1, SERPINB2, SERPINB3, SLC2A3, SLPI, TCN1, THEM4, TIMP1, TUBA4A, TXNDC5
HSA-1280215	Cytokine signaling in immune system	1.98E-06	ABCE1, ANXA1, CDKN1A, CFL1, CNN2, CXCL8, DUSP6, EGR1, EIF4A1, GBP6, HIF1A, HLA-DPB1, HSPA8, IFI27, IL1B, IL1RN, IL20, IL2RA, IL36G, IL36RN, IL6, IL7R, JUNB, KPNA2, LCN2, MCL1, MMP1, MT2A, MYC, MYD88, NDC1, PSMA6, PSMD11, PSME3, PTGS2, S100A12, SERPINB2, TIMP1
HSA-6798695	Neutrophil degranulation	2.81E-06	CDA, CNN2, CTSC, FABP5, GLIPR1, GMFG, GSTP1, HPSE, HRNR, HSPA8, JUP, LCN2, PGAM1, PKM, PLAC8, PLAUR, PNP, PRSS3, PSMD11, PYGL, S100A12, S100A7, S100A8, S100A9, SELL, SERPINB1, SERPINB3, SLC2A3, SLPI, TCN1, TXNDC5
HSA-5362517	Signaling by interleukins	6.40E-06	ANXA1, CDKN1A, CFL1, CNN2, CXCL8, DUSP6, HIF1A, HSPA8, IL1B, IL1RN, IL20, IL2RA, IL36G, IL36RN, IL6, IL7R, JUNB, LCN2, MCL1, MMP1, MYC, MYD88, PSMA6, PSMD11, PSME3, PTGS2, S100A12, SERPINB2, TIMP1