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: IKBKB

Gene summary for IKBKB

Gene summary.

Gene information	Species	Human
	Gene symbol	IKBKB
	Gene ID	3551
	Gene name	inhibitor of nuclear factor kappa B kinase subunit beta
	Gene Alias	IKK-beta
	Cytomap	8p11.21
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	O14920

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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
3551	IKBKB	LZE2T	Human	Esophagus	ESCC	4.29e-02	3.44e-01	0.082
3551	IKBKB	LZE4T	Human	Esophagus	ESCC	3.76e-12	2.65e-01	0.0811
3551	IKBKB	LZE8T	Human	Esophagus	ESCC	6.21e-04	1.19e-01	0.067
3551	IKBKB	LZE20T	Human	Esophagus	ESCC	2.29e-11	3.84e-01	0.0662
3551	IKBKB	LZE24T	Human	Esophagus	ESCC	3.41e-15	3.38e-01	0.0596
3551	IKBKB	LZE21T	Human	Esophagus	ESCC	7.52e-09	3.58e-01	0.0655
3551	IKBKB	P1T-E	Human	Esophagus	ESCC	9.06e-07	3.93e-01	0.0875
3551	IKBKB	P2T-E	Human	Esophagus	ESCC	7.52e-16	3.11e-01	0.1177
3551	IKBKB	P4T-E	Human	Esophagus	ESCC	4.30e-14	2.93e-01	0.1323
3551	IKBKB	P5T-E	Human	Esophagus	ESCC	3.02e-04	3.61e-02	0.1327
3551	IKBKB	P8T-E	Human	Esophagus	ESCC	1.76e-15	2.81e-01	0.0889
3551	IKBKB	P9T-E	Human	Esophagus	ESCC	2.37e-07	1.95e-01	0.1131
3551	IKBKB	P10T-E	Human	Esophagus	ESCC	2.81e-25	2.92e-01	0.116
3551	IKBKB	P11T-E	Human	Esophagus	ESCC	7.73e-07	3.05e-01	0.1426
3551	IKBKB	P12T-E	Human	Esophagus	ESCC	7.96e-20	3.84e-01	0.1122
3551	IKBKB	P15T-E	Human	Esophagus	ESCC	1.40e-29	6.03e-01	0.1149
3551	IKBKB	P16T-E	Human	Esophagus	ESCC	4.67e-34	6.78e-01	0.1153
3551	IKBKB	P17T-E	Human	Esophagus	ESCC	2.13e-05	1.52e-01	0.1278
3551	IKBKB	P20T-E	Human	Esophagus	ESCC	6.16e-27	5.00e-01	0.1124
3551	IKBKB	P21T-E	Human	Esophagus	ESCC	8.29e-09	1.39e-01	0.1617

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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
Thyroid		ATC: Anaplastic thyroid cancer
		HT: Hashimoto's thyroiditis
		PTC: Papillary thyroid cancer

∗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:0072659110	Esophagus	ESCC	protein localization to plasma membrane	193/8552	284/18723	1.95e-14	1.03e-12	193
GO:000961518	Esophagus	ESCC	response to virus	238/8552	367/18723	6.65e-14	3.32e-12	238
GO:199077819	Esophagus	ESCC	protein localization to cell periphery	217/8552	333/18723	4.08e-13	1.88e-11	217
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:0010563111	Esophagus	ESCC	negative regulation of phosphorus metabolic process	274/8552	442/18723	2.32e-12	9.41e-11	274
GO:0045936111	Esophagus	ESCC	negative regulation of phosphate metabolic process	273/8552	441/18723	3.18e-12	1.25e-10	273
GO:0043122110	Esophagus	ESCC	regulation of I-kappaB kinase/NF-kappaB signaling	167/8552	249/18723	6.11e-12	2.32e-10	167
GO:000724919	Esophagus	ESCC	I-kappaB kinase/NF-kappaB signaling	183/8552	281/18723	3.02e-11	1.01e-09	183
GO:001631110	Esophagus	ESCC	dephosphorylation	251/8552	417/18723	1.26e-09	2.99e-08	251
GO:000647018	Esophagus	ESCC	protein dephosphorylation	177/8552	281/18723	3.13e-09	6.72e-08	177
GO:003109818	Esophagus	ESCC	stress-activated protein kinase signaling cascade	154/8552	247/18723	8.53e-08	1.44e-06	154
GO:0035304111	Esophagus	ESCC	regulation of protein dephosphorylation	66/8552	90/18723	8.82e-08	1.48e-06	66
GO:0035303111	Esophagus	ESCC	regulation of dephosphorylation	88/8552	128/18723	1.04e-07	1.71e-06	88
GO:00510908	Esophagus	ESCC	regulation of DNA-binding transcription factor activity	252/8552	440/18723	5.22e-07	6.97e-06	252
GO:005140318	Esophagus	ESCC	stress-activated MAPK cascade	147/8552	239/18723	5.43e-07	7.18e-06	147
GO:000206420	Esophagus	ESCC	epithelial cell development	136/8552	220/18723	9.50e-07	1.21e-05	136
GO:00028318	Esophagus	ESCC	regulation of response to biotic stimulus	191/8552	327/18723	2.12e-06	2.45e-05	191
GO:00182099	Esophagus	ESCC	peptidyl-serine modification	196/8552	338/18723	3.07e-06	3.47e-05	196
GO:00607595	Esophagus	ESCC	regulation of response to cytokine stimulus	103/8552	162/18723	3.14e-06	3.53e-05	103
GO:001810515	Esophagus	ESCC	peptidyl-serine phosphorylation	184/8552	315/18723	3.22e-06	3.61e-05	184

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05132211	Esophagus	ESCC	Salmonella infection	191/4205	249/8465	6.51e-19	5.45e-17	2.79e-17	191
hsa05208211	Esophagus	ESCC	Chemical carcinogenesis - reactive oxygen species	168/4205	223/8465	1.83e-15	6.81e-14	3.49e-14	168
hsa05010210	Esophagus	ESCC	Alzheimer disease	263/4205	384/8465	1.80e-14	5.47e-13	2.80e-13	263
hsa04932210	Esophagus	ESCC	Non-alcoholic fatty liver disease	122/4205	155/8465	5.69e-14	1.59e-12	8.14e-13	122
hsa05166211	Esophagus	ESCC	Human T-cell leukemia virus 1 infection	164/4205	222/8465	8.13e-14	2.09e-12	1.07e-12	164
hsa05169210	Esophagus	ESCC	Epstein-Barr virus infection	151/4205	202/8465	1.55e-13	3.45e-12	1.77e-12	151
hsa05418211	Esophagus	ESCC	Fluid shear stress and atherosclerosis	109/4205	139/8465	2.00e-12	3.72e-11	1.90e-11	109
hsa05131211	Esophagus	ESCC	Shigellosis	176/4205	247/8465	2.27e-12	4.01e-11	2.05e-11	176
hsa05130211	Esophagus	ESCC	Pathogenic Escherichia coli infection	142/4205	197/8465	8.21e-11	1.06e-09	5.42e-10	142
hsa0466810	Esophagus	ESCC	TNF signaling pathway	89/4205	114/8465	3.36e-10	4.01e-09	2.06e-09	89
hsa0421027	Esophagus	ESCC	Apoptosis	102/4205	136/8465	1.05e-09	1.21e-08	6.21e-09	102
hsa05170210	Esophagus	ESCC	Human immunodeficiency virus 1 infection	147/4205	212/8465	3.37e-09	3.53e-08	1.81e-08	147
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
hsa0521216	Esophagus	ESCC	Pancreatic cancer	62/4205	76/8465	7.37e-09	6.85e-08	3.51e-08	62
hsa0516510	Esophagus	ESCC	Human papillomavirus infection	215/4205	331/8465	7.86e-09	7.12e-08	3.65e-08	215
hsa0513526	Esophagus	ESCC	Yersinia infection	100/4205	137/8465	1.80e-08	1.59e-07	8.12e-08	100
hsa05171211	Esophagus	ESCC	Coronavirus disease - COVID-19	156/4205	232/8465	3.18e-08	2.68e-07	1.37e-07	156
hsa0522020	Esophagus	ESCC	Chronic myeloid leukemia	61/4205	76/8465	3.20e-08	2.68e-07	1.37e-07	61
hsa05417211	Esophagus	ESCC	Lipid and atherosclerosis	143/4205	215/8465	3.30e-07	2.45e-06	1.26e-06	143

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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

IKBKB

SNV

Missense_Mutation

c.1703G>T

p.Arg568Met

p.R568M

O14920

protein_coding

tolerated(0.17)

benign(0.015)

TCGA-A1-A0SM-01

Breast

breast invasive carcinoma

Male

>=65

I/II

Unknown

IKBKB

SNV

Missense_Mutation

c.1552N>A

p.Glu518Lys

p.E518K

O14920

protein_coding

deleterious(0.02)

possibly_damaging(0.758)

TCGA-A1-A0SO-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

IKBKB

SNV

Missense_Mutation

c.2068N>G

p.Gln690Glu

p.Q690E

O14920

protein_coding

tolerated(0.46)

benign(0.127)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

IKBKB

SNV

Missense_Mutation

c.742N>T

p.Asp248Tyr

p.D248Y

O14920

protein_coding

deleterious(0)

probably_damaging(0.989)

TCGA-BH-A0BZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

IKBKB

insertion

Nonsense_Mutation

novel

c.76_77insGTAAAGAAACACGTGACCTCGGCGATGCTCAGAAGTAGG

p.Phe26delinsCysLysGluThrArgAspLeuGlyAspAlaGlnLysTerVal

p.F26delinsCKETRDLGDAQK*V

O14920

protein_coding

TCGA-BH-A0B8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

IKBKB

SNV

Missense_Mutation

c.1557N>T

p.Gln519His

p.Q519H

O14920

protein_coding

deleterious(0)

possibly_damaging(0.885)

TCGA-EK-A2PM-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

IKBKB

SNV

Missense_Mutation

c.1008G>C

p.Leu336Phe

p.L336F

O14920

protein_coding

deleterious(0)

possibly_damaging(0.483)

TCGA-Q1-A73O-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

IKBKB

SNV

Missense_Mutation

c.782N>G

p.Tyr261Cys

p.Y261C

O14920

protein_coding

tolerated(0.18)

benign(0.007)

TCGA-AA-3663-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

IKBKB

SNV

Missense_Mutation

novel

c.1820N>G

p.Val607Gly

p.V607G

O14920

protein_coding

tolerated(0.07)

benign(0.01)

TCGA-AA-3692-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Chemotherapy

folinic

IKBKB

SNV

Missense_Mutation

novel

c.1027N>A

p.Asp343Asn

p.D343N

O14920

protein_coding

deleterious(0.03)

benign(0.007)

TCGA-AA-3975-01

Colorectum

colon adenocarcinoma

Male

>=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
3551	IKBKB	SERINE THREONINE KINASE, KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, ENZYME		MLN-0415	MLN-0415
3551	IKBKB	SERINE THREONINE KINASE, KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, ENZYME		IMD-1041	IMD-1041
3551	IKBKB	SERINE THREONINE KINASE, KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, ENZYME		Arsenic trioxide
3551	IKBKB	SERINE THREONINE KINASE, KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, ENZYME	inhibitor	CHEMBL3545265	MLN-0415
3551	IKBKB	SERINE THREONINE KINASE, KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, ENZYME		Parthenolide	PARTHENOLIDE
3551	IKBKB	SERINE THREONINE KINASE, KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, ENZYME		6-METHOXYCOMAPARVIN 5-METHYL ETHER	CHEMBL256967	18088098
3551	IKBKB	SERINE THREONINE KINASE, KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, ENZYME	inhibitor	CHEMBL3545168	IMD-1041
3551	IKBKB	SERINE THREONINE KINASE, KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, ENZYME		6-METHOXYCOMAPARVIN	CHEMBL401565	18088098
3551	IKBKB	SERINE THREONINE KINASE, KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, ENZYME		BMS-345541	BMS-345541	18702457
3551	IKBKB	SERINE THREONINE KINASE, KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, ENZYME		ALSTERPAULLONE	ALSTERPAULLONE

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