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: NFKB1

Gene summary for NFKB1

Gene summary.

Gene information	Species	Human
	Gene symbol	NFKB1
	Gene ID	4790
	Gene name	nuclear factor kappa B subunit 1
	Gene Alias	CVID12
	Cytomap	4q24
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	A0A024RDJ4

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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
4790	NFKB1	HTA11_347_2000001011	Human	Colorectum	AD	1.56e-05	3.93e-01	-0.1954
4790	NFKB1	HTA11_99999974143_84620	Human	Colorectum	MSS	1.05e-03	-2.30e-01	0.3005
4790	NFKB1	A002-C-010	Human	Colorectum	FAP	1.80e-03	-1.58e-01	0.242
4790	NFKB1	A015-C-203	Human	Colorectum	FAP	3.63e-28	-4.81e-01	-0.1294
4790	NFKB1	A015-C-204	Human	Colorectum	FAP	4.98e-04	-3.20e-01	-0.0228
4790	NFKB1	A002-C-201	Human	Colorectum	FAP	2.60e-10	-4.05e-01	0.0324
4790	NFKB1	A002-C-203	Human	Colorectum	FAP	1.46e-05	-2.57e-01	0.2786
4790	NFKB1	A001-C-119	Human	Colorectum	FAP	6.04e-10	-5.20e-01	-0.1557
4790	NFKB1	A001-C-108	Human	Colorectum	FAP	3.76e-19	-3.60e-01	-0.0272
4790	NFKB1	A002-C-205	Human	Colorectum	FAP	4.11e-18	-5.38e-01	-0.1236
4790	NFKB1	A001-C-104	Human	Colorectum	FAP	2.68e-06	-3.20e-01	0.0184
4790	NFKB1	A015-C-005	Human	Colorectum	FAP	6.18e-03	-3.03e-01	-0.0336
4790	NFKB1	A015-C-006	Human	Colorectum	FAP	4.79e-14	-5.61e-01	-0.0994
4790	NFKB1	A015-C-106	Human	Colorectum	FAP	5.44e-10	-3.39e-01	-0.0511
4790	NFKB1	A002-C-114	Human	Colorectum	FAP	2.35e-15	-5.09e-01	-0.1561
4790	NFKB1	A015-C-104	Human	Colorectum	FAP	9.64e-31	-5.06e-01	-0.1899
4790	NFKB1	A001-C-014	Human	Colorectum	FAP	6.13e-18	-3.68e-01	0.0135
4790	NFKB1	A002-C-016	Human	Colorectum	FAP	1.34e-24	-4.35e-01	0.0521
4790	NFKB1	A015-C-002	Human	Colorectum	FAP	9.49e-11	-5.36e-01	-0.0763
4790	NFKB1	A001-C-007	Human	Colorectum	CRC	2.34e-06	-5.98e-01	0.1899

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
Prostate		BPH: Benign Prostatic Hyperplasia
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ
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:1901653	Colorectum	AD	cellular response to peptide	114/3918	359/18723	8.32e-07	2.88e-05	114
GO:0071375	Colorectum	AD	cellular response to peptide hormone stimulus	95/3918	290/18723	1.50e-06	4.66e-05	95
GO:0043434	Colorectum	AD	response to peptide hormone	126/3918	414/18723	2.70e-06	7.86e-05	126
GO:0030111	Colorectum	AD	regulation of Wnt signaling pathway	102/3918	328/18723	8.51e-06	2.03e-04	102
GO:0016055	Colorectum	AD	Wnt signaling pathway	130/3918	444/18723	1.60e-05	3.37e-04	130
GO:0198738	Colorectum	AD	cell-cell signaling by wnt	130/3918	446/18723	2.02e-05	4.10e-04	130
GO:0006066	Colorectum	AD	alcohol metabolic process	106/3918	353/18723	3.02e-05	5.57e-04	106
GO:0060070	Colorectum	AD	canonical Wnt signaling pathway	90/3918	303/18723	1.76e-04	2.38e-03	90
GO:0071496	Colorectum	AD	cellular response to external stimulus	94/3918	320/18723	1.98e-04	2.64e-03	94
GO:0060828	Colorectum	AD	regulation of canonical Wnt signaling pathway	77/3918	253/18723	2.19e-04	2.87e-03	77
GO:0051403	Colorectum	AD	stress-activated MAPK cascade	72/3918	239/18723	4.77e-04	5.25e-03	72
GO:0031098	Colorectum	AD	stress-activated protein kinase signaling cascade	74/3918	247/18723	4.80e-04	5.27e-03	74
GO:0006109	Colorectum	AD	regulation of carbohydrate metabolic process	55/3918	178/18723	1.10e-03	1.01e-02	55
GO:0030177	Colorectum	AD	positive regulation of Wnt signaling pathway	45/3918	140/18723	1.23e-03	1.09e-02	45
GO:0062012	Colorectum	AD	regulation of small molecule metabolic process	93/3918	334/18723	1.46e-03	1.24e-02	93
GO:0010876	Colorectum	AD	lipid localization	120/3918	448/18723	1.59e-03	1.33e-02	120
GO:0006869	Colorectum	AD	lipid transport	108/3918	398/18723	1.67e-03	1.39e-02	108
GO:0008202	Colorectum	AD	steroid metabolic process	85/3918	319/18723	8.07e-03	4.75e-02	85
GO:00301112	Colorectum	MSS	regulation of Wnt signaling pathway	98/3467	328/18723	3.37e-07	1.36e-05	98
GO:00160552	Colorectum	MSS	Wnt signaling pathway	124/3467	444/18723	6.06e-07	2.26e-05	124

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05208	Colorectum	AD	Chemical carcinogenesis - reactive oxygen species	126/2092	223/8465	1.01e-24	1.68e-22	1.07e-22	126
hsa05415	Colorectum	AD	Diabetic cardiomyopathy	114/2092	203/8465	3.65e-22	3.06e-20	1.95e-20	114
hsa05010	Colorectum	AD	Alzheimer disease	174/2092	384/8465	1.82e-19	9.26e-18	5.91e-18	174
hsa04932	Colorectum	AD	Non-alcoholic fatty liver disease	90/2092	155/8465	4.83e-19	1.80e-17	1.15e-17	90
hsa05022	Colorectum	AD	Pathways of neurodegeneration - multiple diseases	201/2092	476/8465	4.54e-18	1.27e-16	8.09e-17	201
hsa05171	Colorectum	AD	Coronavirus disease - COVID-19	113/2092	232/8465	9.90e-16	2.55e-14	1.63e-14	113
hsa05131	Colorectum	AD	Shigellosis	109/2092	247/8465	1.09e-11	2.44e-10	1.55e-10	109
hsa05132	Colorectum	AD	Salmonella infection	102/2092	249/8465	7.65e-09	1.28e-07	8.17e-08	102
hsa05130	Colorectum	AD	Pathogenic Escherichia coli infection	79/2092	197/8465	1.05e-06	1.36e-05	8.65e-06	79
hsa05135	Colorectum	AD	Yersinia infection	58/2092	137/8465	3.90e-06	4.35e-05	2.78e-05	58
hsa04066	Colorectum	AD	HIF-1 signaling pathway	48/2092	109/8465	7.25e-06	7.84e-05	5.00e-05	48
hsa04722	Colorectum	AD	Neurotrophin signaling pathway	50/2092	119/8465	2.28e-05	2.24e-04	1.43e-04	50
hsa05418	Colorectum	AD	Fluid shear stress and atherosclerosis	54/2092	139/8465	1.41e-04	1.16e-03	7.37e-04	54
hsa05417	Colorectum	AD	Lipid and atherosclerosis	73/2092	215/8465	1.31e-03	8.27e-03	5.27e-03	73
hsa05170	Colorectum	AD	Human immunodeficiency virus 1 infection	72/2092	212/8465	1.40e-03	8.46e-03	5.39e-03	72
hsa05220	Colorectum	AD	Chronic myeloid leukemia	31/2092	76/8465	1.41e-03	8.46e-03	5.39e-03	31
hsa05163	Colorectum	AD	Human cytomegalovirus infection	75/2092	225/8465	2.00e-03	1.10e-02	7.01e-03	75
hsa05160	Colorectum	AD	Hepatitis C	54/2092	157/8465	3.87e-03	1.96e-02	1.25e-02	54
hsa04071	Colorectum	AD	Sphingolipid signaling pathway	43/2092	121/8465	4.83e-03	2.28e-02	1.45e-02	43
hsa05166	Colorectum	AD	Human T-cell leukemia virus 1 infection	72/2092	222/8465	5.24e-03	2.44e-02	1.55e-02	72

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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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
NFKB1	SMC	Cervix	Healthy	SOD2,CXCL2,NFKB2, etc.	8.36e-01
NFKB1	IMENT	Colorectum	MSS	TNFRSF6B,IRF1,C8orf4, etc.	4.29e-02
NFKB1	AT2	Lung	IAC	DENND4A,BACH1,KYNU, etc.	1.83e-01
NFKB1	LC	Lung	IAC	SIPA1L1,AL078604.4,KYNU, etc.	2.62e-01
NFKB1	M2MAC	Skin	Healthy	REL,ATP5F1E,SIPA1L1, etc.	4.68e-01
NFKB1	M2MAC	Skin	SCCIS	REL,ATP5F1E,SIPA1L1, etc.	2.92e-01

∗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

NFKB1

SNV

Missense_Mutation

c.1715C>T

p.Ser572Phe

p.S572F

P19838

protein_coding

tolerated(0.64)

benign(0.201)

TCGA-A2-A0YH-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

NFKB1

SNV

Missense_Mutation

novel

c.2191N>A

p.Gly731Arg

p.G731R

P19838

protein_coding

deleterious(0)

probably_damaging(0.984)

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

NFKB1

SNV

Missense_Mutation

novel

c.119C>G

p.Ala40Gly

p.A40G

P19838

protein_coding

tolerated(0.07)

possibly_damaging(0.854)

TCGA-AR-A0U0-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NFKB1

SNV

Missense_Mutation

novel

c.733N>A

p.Ala245Thr

p.A245T

P19838

protein_coding

deleterious(0)

probably_damaging(0.942)

TCGA-AR-A24L-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

NFKB1

SNV

Missense_Mutation

rs865962183

c.574N>T

p.Arg192Trp

p.R192W

P19838

protein_coding

deleterious(0.01)

probably_damaging(0.972)

TCGA-AR-A256-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

NFKB1

SNV

Missense_Mutation

c.221C>G

p.Ser74Cys

p.S74C

P19838

protein_coding

deleterious(0)

probably_damaging(0.935)

TCGA-E2-A1LH-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

NFKB1

SNV

Missense_Mutation

rs769204159

c.1562N>T

p.Ala521Val

p.A521V

P19838

protein_coding

tolerated(0.06)

probably_damaging(0.988)

TCGA-E2-A573-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

NFKB1

SNV

Missense_Mutation

novel

c.1308N>T

p.Met436Ile

p.M436I

P19838

protein_coding

tolerated(0.25)

benign(0)

TCGA-HN-A2OB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

fluorouracil

NFKB1

insertion

Nonsense_Mutation

novel

c.2107_2108insTTCTAAATATCTACTAGGTATTTGATAAACGTGTGTTATTT

p.Gly703ValfsTer6

p.G703Vfs*6

P19838

protein_coding

TCGA-A2-A04Q-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

NFKB1

insertion

Frame_Shift_Ins

novel

c.1403_1404insGTTTTTTCCT

p.Asp469PhefsTer16

p.D469Ffs*16

P19838

protein_coding

TCGA-AO-A03O-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

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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
4790	NFKB1	KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME		SJ000113257	CHEMBL528694
4790	NFKB1	KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME		SANGUINARIUM	SANGUINARIUM
4790	NFKB1	KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME		DYRENE	DYRENE
4790	NFKB1	KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME		ISORHAMNETIN	ISORHAMNETIN	25190466
4790	NFKB1	KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME		MITOXANTRONE	MITOXANTRONE
4790	NFKB1	KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME		PARTHENOLIDE	PARTHENOLIDE	25190466
4790	NFKB1	KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME		THALIDOMIDE	THALIDOMIDE
4790	NFKB1	KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME		(S)-NOMIFENSINE	CHEMBL51697
4790	NFKB1	KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME		6-CHLOROMELATONIN	CHEMBL34730
4790	NFKB1	KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME		TOSYL-L-LYSINE CHLOROMETHYL KETONE	CHEMBL466465

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