Schematic overview of the cellular and molecular mechanisms involved in the cancer progression, including the proposed cellular and molecular mechanisms in cancer cells trajectory. AT1: alveolar type 1 cells; AT2: alveolar type 2 cells; AAH: atypical adenomatous hyperplasia; AIS: adenocarcinoma in situ; MIA: minimally invasive adenocarcinoma; IA: invasive adenocarcinoma; EMT: epithelial-mesenchymal transition

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	Gene summary
	Malignant transformation analysis
	Malignant transformation related pathway analysis
	Cell-cell communication analysis
	Single-cell gene regulatory network inference analysis
	Somatic mutation of malignant transformation related genes
	Related drugs of malignant transformation related genes

Gene: IKBKE

Gene summary for IKBKE

Gene summary.

Gene information	Species	Human
	Gene symbol	IKBKE
	Gene ID	9641
	Gene name	inhibitor of nuclear factor kappa B kinase subunit epsilon
	Gene Alias	IKK-E
	Cytomap	1q32.1
	Gene Type	protein-coding
	GO ID	GO:0001959
	UniProtAcc	Q14164

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Malignant transformation analysis

Identification of the aberrant gene expression in precancerous and cancerous lesions by comparing the gene expression of stem-like cells in diseased tissues with normal stem cells

Malignant transformation involving gene list.

Entrez ID	Symbol	Replicates	Species	Organ	Tissue	Adj P-value	Log2FC	Malignancy
9641	IKBKE	LZE7T	Human	Esophagus	ESCC	7.50e-05	3.05e-01	0.0667
9641	IKBKE	LZE24T	Human	Esophagus	ESCC	3.06e-04	1.44e-01	0.0596
9641	IKBKE	P1T-E	Human	Esophagus	ESCC	2.42e-05	2.65e-01	0.0875
9641	IKBKE	P2T-E	Human	Esophagus	ESCC	3.77e-11	3.02e-01	0.1177
9641	IKBKE	P4T-E	Human	Esophagus	ESCC	3.72e-12	3.15e-01	0.1323
9641	IKBKE	P5T-E	Human	Esophagus	ESCC	3.48e-08	2.30e-01	0.1327
9641	IKBKE	P9T-E	Human	Esophagus	ESCC	2.48e-04	1.23e-01	0.1131
9641	IKBKE	P15T-E	Human	Esophagus	ESCC	1.73e-02	1.16e-01	0.1149
9641	IKBKE	P20T-E	Human	Esophagus	ESCC	2.39e-06	1.95e-01	0.1124
9641	IKBKE	P21T-E	Human	Esophagus	ESCC	6.18e-08	2.32e-01	0.1617
9641	IKBKE	P22T-E	Human	Esophagus	ESCC	2.45e-14	2.40e-01	0.1236
9641	IKBKE	P23T-E	Human	Esophagus	ESCC	8.44e-15	3.69e-01	0.108
9641	IKBKE	P24T-E	Human	Esophagus	ESCC	1.34e-05	1.37e-01	0.1287
9641	IKBKE	P26T-E	Human	Esophagus	ESCC	4.57e-10	3.19e-01	0.1276
9641	IKBKE	P28T-E	Human	Esophagus	ESCC	6.01e-03	1.43e-01	0.1149
9641	IKBKE	P30T-E	Human	Esophagus	ESCC	8.83e-09	3.43e-01	0.137
9641	IKBKE	P31T-E	Human	Esophagus	ESCC	9.38e-08	1.06e-01	0.1251
9641	IKBKE	P32T-E	Human	Esophagus	ESCC	5.05e-07	1.79e-01	0.1666
9641	IKBKE	P36T-E	Human	Esophagus	ESCC	1.22e-04	2.33e-01	0.1187
9641	IKBKE	P37T-E	Human	Esophagus	ESCC	5.28e-11	2.20e-01	0.1371

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma

∗log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.

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Malignant transformation related pathway analysis

Find out the enriched GO biological processes and KEGG pathways involved in transition from healthy to precancer to cancer

Figure of enriched GO biological processes.

Tissue	Disease Stage	Enriched GO biological Processes
Colorectum	AD
Colorectum	SER
Colorectum	MSS
Colorectum	MSI-H
Colorectum	FAP

∗Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).

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Enriched GO biological processes.

GO ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	Count
GO:0097193111	Esophagus	ESCC	intrinsic apoptotic signaling pathway	222/8552	288/18723	5.87e-28	2.02e-25	222
GO:1903311110	Esophagus	ESCC	regulation of mRNA metabolic process	210/8552	288/18723	3.25e-21	5.56e-19	210
GO:0006401110	Esophagus	ESCC	RNA catabolic process	204/8552	278/18723	3.39e-21	5.66e-19	204
GO:0034655110	Esophagus	ESCC	nucleobase-containing compound catabolic process	272/8552	407/18723	2.92e-18	2.90e-16	272
GO:0006402110	Esophagus	ESCC	mRNA catabolic process	170/8552	232/18723	8.70e-18	8.00e-16	170
GO:0043254111	Esophagus	ESCC	regulation of protein-containing complex assembly	278/8552	428/18723	3.81e-16	2.77e-14	278
GO:004670018	Esophagus	ESCC	heterocycle catabolic process	286/8552	445/18723	1.12e-15	7.47e-14	286
GO:004427019	Esophagus	ESCC	cellular nitrogen compound catabolic process	288/8552	451/18723	3.03e-15	1.79e-13	288
GO:001943918	Esophagus	ESCC	aromatic compound catabolic process	295/8552	467/18723	1.09e-14	5.98e-13	295
GO:000961518	Esophagus	ESCC	response to virus	238/8552	367/18723	6.65e-14	3.32e-12	238
GO:190136118	Esophagus	ESCC	organic cyclic compound catabolic process	307/8552	495/18723	9.99e-14	4.80e-12	307
GO:004312318	Esophagus	ESCC	positive regulation of I-kappaB kinase/NF-kappaB signaling	132/8552	186/18723	2.07e-12	8.58e-11	132
GO:0043122110	Esophagus	ESCC	regulation of I-kappaB kinase/NF-kappaB signaling	167/8552	249/18723	6.11e-12	2.32e-10	167
GO:0008630110	Esophagus	ESCC	intrinsic apoptotic signaling pathway in response to DNA damage	78/8552	99/18723	1.43e-11	5.08e-10	78
GO:000724919	Esophagus	ESCC	I-kappaB kinase/NF-kappaB signaling	183/8552	281/18723	3.02e-11	1.01e-09	183
GO:0009895111	Esophagus	ESCC	negative regulation of catabolic process	201/8552	320/18723	3.88e-10	1.05e-08	201
GO:006101319	Esophagus	ESCC	regulation of mRNA catabolic process	115/8552	166/18723	5.90e-10	1.49e-08	115
GO:004348719	Esophagus	ESCC	regulation of RNA stability	117/8552	170/18723	7.91e-10	1.94e-08	117
GO:004348819	Esophagus	ESCC	regulation of mRNA stability	109/8552	158/18723	2.40e-09	5.35e-08	109
GO:0031330111	Esophagus	ESCC	negative regulation of cellular catabolic process	166/8552	262/18723	5.17e-09	1.08e-07	166

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05169210	Esophagus	ESCC	Epstein-Barr virus infection	151/4205	202/8465	1.55e-13	3.45e-12	1.77e-12	151
hsa05167211	Esophagus	ESCC	Kaposi sarcoma-associated herpesvirus infection	136/4205	194/8465	4.28e-09	4.22e-08	2.16e-08	136
hsa0516425	Esophagus	ESCC	Influenza A	122/4205	171/8465	5.01e-09	4.79e-08	2.45e-08	122
hsa0516510	Esophagus	ESCC	Human papillomavirus infection	215/4205	331/8465	7.86e-09	7.12e-08	3.65e-08	215
hsa05171211	Esophagus	ESCC	Coronavirus disease - COVID-19	156/4205	232/8465	3.18e-08	2.68e-07	1.37e-07	156
hsa05417211	Esophagus	ESCC	Lipid and atherosclerosis	143/4205	215/8465	3.30e-07	2.45e-06	1.26e-06	143
hsa051609	Esophagus	ESCC	Hepatitis C	107/4205	157/8465	1.75e-06	1.08e-05	5.55e-06	107
hsa051619	Esophagus	ESCC	Hepatitis B	108/4205	162/8465	7.68e-06	4.15e-05	2.12e-05	108
hsa046259	Esophagus	ESCC	C-type lectin receptor signaling pathway	73/4205	104/8465	1.57e-05	7.98e-05	4.09e-05	73
hsa0465727	Esophagus	ESCC	IL-17 signaling pathway	66/4205	94/8465	3.93e-05	1.75e-04	8.99e-05	66
hsa051629	Esophagus	ESCC	Measles	90/4205	139/8465	2.16e-04	7.87e-04	4.03e-04	90
hsa0462122	Esophagus	ESCC	NOD-like receptor signaling pathway	116/4205	186/8465	2.90e-04	1.03e-03	5.30e-04	116
hsa046234	Esophagus	ESCC	Cytosolic DNA-sensing pathway	49/4205	75/8465	4.35e-03	1.12e-02	5.74e-03	49
hsa0516937	Esophagus	ESCC	Epstein-Barr virus infection	151/4205	202/8465	1.55e-13	3.45e-12	1.77e-12	151
hsa0516738	Esophagus	ESCC	Kaposi sarcoma-associated herpesvirus infection	136/4205	194/8465	4.28e-09	4.22e-08	2.16e-08	136
hsa0516435	Esophagus	ESCC	Influenza A	122/4205	171/8465	5.01e-09	4.79e-08	2.45e-08	122
hsa0516515	Esophagus	ESCC	Human papillomavirus infection	215/4205	331/8465	7.86e-09	7.12e-08	3.65e-08	215
hsa05171310	Esophagus	ESCC	Coronavirus disease - COVID-19	156/4205	232/8465	3.18e-08	2.68e-07	1.37e-07	156
hsa05417310	Esophagus	ESCC	Lipid and atherosclerosis	143/4205	215/8465	3.30e-07	2.45e-06	1.26e-06	143
hsa0516016	Esophagus	ESCC	Hepatitis C	107/4205	157/8465	1.75e-06	1.08e-05	5.55e-06	107

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Cell-cell communication analysis

Identification of potential cell-cell interactions between two cell types and their ligand-receptor pairs for different disease states

Ligand

Receptor

LRpair

Pathway

Tissue

Disease Stage

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Single-cell gene regulatory network inference analysis

Find out the significant the regulons (TFs) and the target genes of each regulon across cell types for different disease states

Cell Type

Tissue

Disease Stage

Target Gene

RSS

Regulon Activity

∗The dot plots of a searched regulon are shown for all cell subpopulations in each disease state of each tissue based on the regulon specific score inferred using pySCENIC and by calculating the average expression.

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Somatic mutation of malignant transformation related genes

Annotation of somatic variants for genes involved in malignant transformation

Hugo Symbol

Variant Class

Variant Classification

dbSNP RS

HGVSc

HGVSp

HGVSp Short

SWISSPROT

BIOTYPE

SIFT

PolyPhen

Tumor Sample Barcode

Tissue

Histology

Sex

Age

Stage

Therapy Types

Drugs

Outcome

IKBKE

SNV

Missense_Mutation

c.297G>C

p.Glu99Asp

p.E99D

Q14164

protein_coding

tolerated(0.05)

possibly_damaging(0.732)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

IKBKE

SNV

Missense_Mutation

c.682C>T

p.Arg228Trp

p.R228W

Q14164

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AR-A0TU-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Doxorubicin

IKBKE

SNV

Missense_Mutation

c.224A>G

p.Glu75Gly

p.E75G

Q14164

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

IKBKE

SNV

Missense_Mutation

rs782109082

c.485G>A

p.Arg162Gln

p.R162Q

Q14164

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

IKBKE

SNV

Missense_Mutation

c.1587N>T

p.Lys529Asn

p.K529N

Q14164

protein_coding

tolerated(0.06)

probably_damaging(0.974)

TCGA-D8-A1JD-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

IKBKE

SNV

Missense_Mutation

novel

c.1342N>A

p.Glu448Lys

p.E448K

Q14164

protein_coding

tolerated(0.14)

benign(0.086)

TCGA-S3-AA15-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

IKBKE

deletion

Frame_Shift_Del

novel

c.308delA

p.Asn103MetfsTer21

p.N103Mfs*21

Q14164

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

IKBKE

SNV

Missense_Mutation

novel

c.466A>G

p.Thr156Ala

p.T156A

Q14164

protein_coding

deleterious(0.02)

benign(0.348)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

IKBKE

SNV

Missense_Mutation

c.740N>T

p.Ala247Val

p.A247V

Q14164

protein_coding

deleterious(0)

probably_damaging(0.917)

TCGA-FU-A3EO-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

IKBKE

SNV

Missense_Mutation

novel

c.406N>G

p.Ile136Val

p.I136V

Q14164

protein_coding

deleterious(0)

possibly_damaging(0.817)

TCGA-VS-A952-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

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Related drugs of malignant transformation related genes

Identification of chemicals and drugs interact with genes involved in malignant transfromation

(DGIdb 4.0)

Entrez ID	Symbol	Category	Interaction Types	Drug Claim Name	Drug Name	PMIDs
9641	IKBKE	DRUGGABLE GENOME, SERINE THREONINE KINASE, KINASE, CLINICALLY ACTIONABLE, ENZYME	inhibitor	336446965
9641	IKBKE	DRUGGABLE GENOME, SERINE THREONINE KINASE, KINASE, CLINICALLY ACTIONABLE, ENZYME		PD-0166285	PD-0166285
9641	IKBKE	DRUGGABLE GENOME, SERINE THREONINE KINASE, KINASE, CLINICALLY ACTIONABLE, ENZYME		TAE-684	TAE-684
9641	IKBKE	DRUGGABLE GENOME, SERINE THREONINE KINASE, KINASE, CLINICALLY ACTIONABLE, ENZYME		AZD-1775	ADAVOSERTIB
9641	IKBKE	DRUGGABLE GENOME, SERINE THREONINE KINASE, KINASE, CLINICALLY ACTIONABLE, ENZYME	inhibitor	178103690	AMLEXANOX
9641	IKBKE	DRUGGABLE GENOME, SERINE THREONINE KINASE, KINASE, CLINICALLY ACTIONABLE, ENZYME		DNDI1417467	CHEMBL1997335
9641	IKBKE	DRUGGABLE GENOME, SERINE THREONINE KINASE, KINASE, CLINICALLY ACTIONABLE, ENZYME	inhibitor	336446966
9641	IKBKE	DRUGGABLE GENOME, SERINE THREONINE KINASE, KINASE, CLINICALLY ACTIONABLE, ENZYME		681640	CHEMBL379975
9641	IKBKE	DRUGGABLE GENOME, SERINE THREONINE KINASE, KINASE, CLINICALLY ACTIONABLE, ENZYME		TAMATINIB	R-406
9641	IKBKE	DRUGGABLE GENOME, SERINE THREONINE KINASE, KINASE, CLINICALLY ACTIONABLE, ENZYME		CENISERTIB	CENISERTIB

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