Table II. Gene sets significantly upregulated in vocal fold fibroblasts (VFF) exposed to control air-bubbled control (ABC) medium versus VFF exposed to cigarette smoke exctract (CSE). Proteomic data from VFF that were harvested 24 h after exposure to CSE or air-bubbled control (ABC) medium was subjected to gene set enrichment analysis (GSEA). The analysis was run with distinct gene sets databases (column 1) obtained from the Molecular Signatures Database. Only gene sets (column 2) that are significantly (FDR q-value <0.1; column 3) enriched among proteins upregulated in ABC- versus CSE-treated cells are depicted. Proteins detected in the samples and having the strongest contribution to the enrichment (“core enrichment”) are shown in column 4 and identified by official symbol.

Gene sets database	Gene sets significantly (FDR q-value < 0.1) enriched in control versus CSE-treated VFF	FDR q-value	Gene symbols of proteins within core enrichment
Positional gene sets	-	-
BIOCARTA	-	-
Chemical and genetic perturbations	LE_EGR2_TARGETS_UP	0.0376	LMNB1, RPA3, EZR, HN1, CD44, BZW2, CSRP2, CORO1C, KPNA2, MCM7, HDAC2, MARCKS, MCM4, RRM1, MCM5
	PUJANA_BREAST_CANCER_WITH_BRCA1_MUTATED_UP	0.0417	CAD, RPA1, DDX39A, STMN1, PNN, MCM4, SRSF11, MCM2, MCM5, MRE11A
	CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_UP	0.0535	HMGB3, RASA1, SSRP1, BZW2, ANP32E, TMSB4X, RANGAP1, UBE2D2, PPAP2B, TIMP1, MYO1B, ITGA6, NAP1L1, RRM1
	KAUFFMANN_DNA_REPLICATION_GENES	0.0554	CTBP2, CTBP1, MCM7, MYBBP1A, NFIC, NAP1L1, MCM4, RRM1, MCM2, MCM5
	LIM_MAMMARY_LUMINAL_MATURE_DN	0.0556	EPB41L2, COL6A1, CALD1, FSTL1, FAS, CYGB, RAP2B, RECK, MAP4K4
	FUJII_YBX1_TARGETS_DN	0.0730	NUP62, RAD23B, MCM7, SSR1, MCM4, RRM1, DFFA, MCM2, MCM5, RECK
	MIKKELSEN_MEF_LCP_WITH_H3K4ME3	0.0736	TRIM21, GBP1, COL6A1, VWA5A, PDGFRB, COL3A1, ECM1
	BURTON_ADIPOGENESIS_3	0.0778	CSRP2, KPNA2, MCM7, MCM4, RRM1, MCM2, MCM5
	CHANG_CYCLING_GENES	0.0793	ANP32E, RANGAP1, TUBB, TIMP1, MCM4, RRM1, MCM5
	BILANGES_SERUM_SENSITIVE_VIA_TSC2	0.0800	GLG1, NPM3, NUMA1, COL1A2, FAM98B, GBF1, COL3A1
	CROONQUIST_IL6_DEPRIVATION_DN	0.0820	STMN1, ANP32E, SNRPA1, KPNA2, MCM7, MCM4, MCM2
	MISSIAGLIA_REGULATED_BY_METHYLATION_DN	0.0947	RANBP1, PRKDC, LMNB1, CAD, RBMX, RPA3, ACAT2, TMPO, CAV1, H2AFV, HMGB3, STMN1, HNRNPL, PSIP1, SNRNP40, RRM1, SRSF3, MCM5
KEGG	-	-
REACTOME	-	-
microRNA targets	-	-
Transcription factor targets	-	-
GO biological process	GO_DNA_REPLICATION	0.0024	MCM7, PARP1, NFIC, NUP98, NAP1L1, MCM4, RRM1, MCM2, MCM5, MRE11A
	GO_DNA_GEOMETRIC_CHANGE	0.0984	RAD23B, MCM7, PARP1, MCM4, MCM2, MCM5, MRE11A
GO cellular component	GO_CHROMOSOME_TELOMERIC_REGION	0.0490	SUN2, MCM7, PARP1, MCM4, MCM2, MCM5, MRE11A
	GO_CELL_CELL_CONTACT_ZONE	0.0531	CTNNA1, ACTN1, FLOT1, PGM5, ANXA6, VCL, CTNNB1, FLOT2, TJP1, ITGB1, AHNAK, ATP1B1, RAP2B
	GO_NUCLEAR_CHROMOSOME_TELOMERIC_REGION	0.0751	SUN2, MCM7, PARP1, MCM4, MCM2, MCM5, MRE11A
	GO_ACTOMYOSIN	0.0826	ACTN1, ACTN4, ACTA1, MYO1C, PGM5, DBN1, PDLIM2, MYO18A, PXN, ZYX, LIMA1, PDLIM7, MYL9, CNN2, TPM4
	GO_CHROMOSOMAL_REGION	0.0912	RANGAP1, SUN2, TPR, MCM7, PARP1, NUP98, MCM4, MCM2, MCM5, MRE11A
GO molecular function	-	-
Oncogenic signatures	ESC_J1_UP_EARLY.V1_DN	0.0135	GBP1, MVK, LUC7L3, VWA5A, ANXA3, MYL9, CIRBP, TAGLN
	ESC_V6.5_UP_EARLY.V1_DN	0.0168	SERPINE1, FHL2, CAV1, CSRP1, CD44, ALCAM, TGFB1I1, ANXA2, COL1A1, VAC14, CALD1, COL1A2, AHNAK, ANXA3, TAGLN, COL3A1
Immunologic signatures	-	-
Hallmark gene sets	HALLMARK_E2F_TARGETS	0.0523	PRKDC, LMNB1, NOP56, AK2, RPA1, RPA3, TMPO, DDX39A, HMGB3, HN1, SSRP1, TRA2B, STMN1, RBBP7, PNN, ANP32E, LUC7L3, PSIP1, TUBB, KPNA2, MCM7, NAP1L1, MCM4, MCM2, MCM5, MRE11A
	HALLMARK_UV_RESPONSE_DN	0.0690	ATP2B4, ADD3, SERPINE1, FHL2, CAV1, PRKCA, TJP1, PDLIM5, ANXA2, COL1A1, MGLL, NFKB1, COL1A2, PPAP2B, RBPMS, PDGFRB, COL3A1