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: CHUK

Gene summary for CHUK

Gene summary.

Gene information	Species	Human
	Gene symbol	CHUK
	Gene ID	1147
	Gene name	component of inhibitor of nuclear factor kappa B kinase complex
	Gene Alias	BPS2
	Cytomap	10q24.31
	Gene Type	protein-coding
	GO ID	GO:0000302
	UniProtAcc	O15111

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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
1147	CHUK	LZE4T	Human	Esophagus	ESCC	2.97e-02	2.40e-02	0.0811
1147	CHUK	LZE7T	Human	Esophagus	ESCC	1.70e-03	1.01e-01	0.0667
1147	CHUK	LZE24T	Human	Esophagus	ESCC	6.74e-05	2.03e-01	0.0596
1147	CHUK	P2T-E	Human	Esophagus	ESCC	1.58e-15	1.46e-01	0.1177
1147	CHUK	P4T-E	Human	Esophagus	ESCC	1.55e-07	1.27e-01	0.1323
1147	CHUK	P5T-E	Human	Esophagus	ESCC	1.18e-13	1.31e-01	0.1327
1147	CHUK	P8T-E	Human	Esophagus	ESCC	3.61e-03	7.08e-02	0.0889
1147	CHUK	P9T-E	Human	Esophagus	ESCC	2.43e-03	2.55e-02	0.1131
1147	CHUK	P10T-E	Human	Esophagus	ESCC	6.32e-04	1.48e-02	0.116
1147	CHUK	P11T-E	Human	Esophagus	ESCC	1.32e-02	5.57e-02	0.1426
1147	CHUK	P12T-E	Human	Esophagus	ESCC	7.11e-09	2.02e-01	0.1122
1147	CHUK	P15T-E	Human	Esophagus	ESCC	4.54e-12	1.82e-01	0.1149
1147	CHUK	P16T-E	Human	Esophagus	ESCC	4.53e-07	1.10e-01	0.1153
1147	CHUK	P17T-E	Human	Esophagus	ESCC	4.40e-03	1.15e-01	0.1278
1147	CHUK	P19T-E	Human	Esophagus	ESCC	4.31e-03	3.00e-01	0.1662
1147	CHUK	P20T-E	Human	Esophagus	ESCC	8.02e-08	1.92e-01	0.1124
1147	CHUK	P21T-E	Human	Esophagus	ESCC	2.77e-09	1.43e-01	0.1617
1147	CHUK	P23T-E	Human	Esophagus	ESCC	4.74e-14	3.00e-01	0.108
1147	CHUK	P24T-E	Human	Esophagus	ESCC	1.80e-09	8.71e-02	0.1287
1147	CHUK	P26T-E	Human	Esophagus	ESCC	9.03e-11	2.38e-01	0.1276

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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

∗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:0006979111	Esophagus	ESCC	response to oxidative stress	303/8552	446/18723	7.15e-22	1.30e-19	303
GO:0062197111	Esophagus	ESCC	cellular response to chemical stress	234/8552	337/18723	5.37e-19	5.97e-17	234
GO:0034599111	Esophagus	ESCC	cellular response to oxidative stress	197/8552	288/18723	3.76e-15	2.15e-13	197
GO:000961518	Esophagus	ESCC	response to virus	238/8552	367/18723	6.65e-14	3.32e-12	238
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:000724919	Esophagus	ESCC	I-kappaB kinase/NF-kappaB signaling	183/8552	281/18723	3.02e-11	1.01e-09	183
GO:0000302111	Esophagus	ESCC	response to reactive oxygen species	150/8552	222/18723	3.06e-11	1.02e-09	150
GO:003461420	Esophagus	ESCC	cellular response to reactive oxygen species	103/8552	155/18723	1.34e-07	2.17e-06	103
GO:000726510	Esophagus	ESCC	Ras protein signal transduction	201/8552	337/18723	1.44e-07	2.30e-06	201
GO:00510908	Esophagus	ESCC	regulation of DNA-binding transcription factor activity	252/8552	440/18723	5.22e-07	6.97e-06	252
GO:00182099	Esophagus	ESCC	peptidyl-serine modification	196/8552	338/18723	3.07e-06	3.47e-05	196
GO:001810515	Esophagus	ESCC	peptidyl-serine phosphorylation	184/8552	315/18723	3.22e-06	3.61e-05	184
GO:00510918	Esophagus	ESCC	positive regulation of DNA-binding transcription factor activity	155/8552	260/18723	3.83e-06	4.14e-05	155
GO:0043434111	Esophagus	ESCC	response to peptide hormone	234/8552	414/18723	4.93e-06	5.21e-05	234
GO:003320914	Esophagus	ESCC	tumor necrosis factor-mediated signaling pathway	67/8552	99/18723	7.87e-06	7.72e-05	67
GO:003461220	Esophagus	ESCC	response to tumor necrosis factor	149/8552	253/18723	1.47e-05	1.33e-04	149
GO:003248112	Esophagus	ESCC	positive regulation of type I interferon production	42/8552	58/18723	3.27e-05	2.70e-04	42
GO:000941020	Esophagus	ESCC	response to xenobiotic stimulus	253/8552	462/18723	4.55e-05	3.58e-04	253
GO:001003827	Esophagus	ESCC	response to metal ion	208/8552	373/18723	5.02e-05	3.90e-04	208

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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
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
hsa052229	Esophagus	ESCC	Small cell lung cancer	69/4205	92/8465	5.40e-07	3.85e-06	1.97e-06	69

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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

CHUK

SNV

Missense_Mutation

rs184250593

c.1654N>T

p.Arg552Cys

p.R552C

O15111

protein_coding

deleterious(0)

probably_damaging(0.925)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CHUK

SNV

Missense_Mutation

novel

c.1513N>A

p.Glu505Lys

p.E505K

O15111

protein_coding

deleterious(0)

probably_damaging(0.985)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CHUK

SNV

Missense_Mutation

rs747387872

c.757N>T

p.Arg253Trp

p.R253W

O15111

protein_coding

deleterious(0)

probably_damaging(0.983)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CHUK

SNV

Missense_Mutation

novel

c.590N>T

p.Pro197Leu

p.P197L

O15111

protein_coding

tolerated(0.08)

possibly_damaging(0.836)

TCGA-AR-A24R-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

CHUK

SNV

Missense_Mutation

novel

c.241G>A

p.Glu81Lys

p.E81K

O15111

protein_coding

deleterious(0.05)

benign(0.138)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CHUK

SNV

Missense_Mutation

novel

c.195G>A

p.Met65Ile

p.M65I

O15111

protein_coding

tolerated(0.07)

benign(0.266)

TCGA-BH-A2L8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

CHUK

SNV

Missense_Mutation

c.1183N>A

p.Glu395Lys

p.E395K

O15111

protein_coding

tolerated(0.09)

benign(0.037)

TCGA-D8-A1JA-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

CHUK

deletion

Frame_Shift_Del

novel

c.2167_2168delNN

p.Ile723TyrfsTer3

p.I723Yfs*3

O15111

protein_coding

TCGA-AC-A3OD-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CHUK

SNV

Missense_Mutation

c.751G>A

p.Glu251Lys

p.E251K

O15111

protein_coding

tolerated(0.08)

probably_damaging(0.936)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CHUK

SNV

Missense_Mutation

c.1395G>C

p.Met465Ile

p.M465I

O15111

protein_coding

deleterious(0.03)

benign(0.119)

TCGA-DG-A2KM-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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
1147	CHUK	SERINE THREONINE KINASE, DRUGGABLE GENOME, ENZYME, KINASE, TRANSCRIPTION FACTOR		N-(3-OXODODECANOYL)HOMOSERINELACTONE	CHEMBL8483	18566250
1147	CHUK	SERINE THREONINE KINASE, DRUGGABLE GENOME, ENZYME, KINASE, TRANSCRIPTION FACTOR		LAUROGUADINE	LAUROGUADINE
1147	CHUK	SERINE THREONINE KINASE, DRUGGABLE GENOME, ENZYME, KINASE, TRANSCRIPTION FACTOR	inhibitor	328083500	CHEMBL592893
1147	CHUK	SERINE THREONINE KINASE, DRUGGABLE GENOME, ENZYME, KINASE, TRANSCRIPTION FACTOR		6R-SENECIONYLCHAPARRIN	CHEMBL564009	19199792
1147	CHUK	SERINE THREONINE KINASE, DRUGGABLE GENOME, ENZYME, KINASE, TRANSCRIPTION FACTOR	inhibitor	340590276
1147	CHUK	SERINE THREONINE KINASE, DRUGGABLE GENOME, ENZYME, KINASE, TRANSCRIPTION FACTOR	inhibitor	348353652
1147	CHUK	SERINE THREONINE KINASE, DRUGGABLE GENOME, ENZYME, KINASE, TRANSCRIPTION FACTOR		GLAUCARUBINONE	GLAUCARUBINONE	19199792
1147	CHUK	SERINE THREONINE KINASE, DRUGGABLE GENOME, ENZYME, KINASE, TRANSCRIPTION FACTOR		PEPEROMIN E	PEPEROMIN E	19559609
1147	CHUK	SERINE THREONINE KINASE, DRUGGABLE GENOME, ENZYME, KINASE, TRANSCRIPTION FACTOR		VITAMIN C		11120850
1147	CHUK	SERINE THREONINE KINASE, DRUGGABLE GENOME, ENZYME, KINASE, TRANSCRIPTION FACTOR	allosteric modulator	178102297	BMS-345541

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