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: NFKB2

Gene summary for NFKB2

Gene summary.

Gene information	Species	Human
	Gene symbol	NFKB2
	Gene ID	4791
	Gene name	nuclear factor kappa B subunit 2
	Gene Alias	CVID10
	Cytomap	10q24.32
	Gene Type	protein-coding
	GO ID	GO:0001775
	UniProtAcc	Q00653

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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
4791	NFKB2	LZE4T	Human	Esophagus	ESCC	2.42e-11	2.07e-01	0.0811
4791	NFKB2	LZE5T	Human	Esophagus	ESCC	4.22e-06	3.16e-01	0.0514
4791	NFKB2	LZE7T	Human	Esophagus	ESCC	6.29e-06	2.62e-01	0.0667
4791	NFKB2	LZE8T	Human	Esophagus	ESCC	1.50e-15	3.80e-01	0.067
4791	NFKB2	LZE20T	Human	Esophagus	ESCC	1.23e-02	1.03e-01	0.0662
4791	NFKB2	LZE22T	Human	Esophagus	ESCC	4.32e-05	2.90e-01	0.068
4791	NFKB2	LZE24T	Human	Esophagus	ESCC	1.38e-23	7.06e-01	0.0596
4791	NFKB2	LZE21T	Human	Esophagus	ESCC	9.66e-06	4.56e-01	0.0655
4791	NFKB2	LZE6T	Human	Esophagus	ESCC	1.99e-03	1.15e-01	0.0845
4791	NFKB2	P1T-E	Human	Esophagus	ESCC	3.64e-24	9.70e-01	0.0875
4791	NFKB2	P2T-E	Human	Esophagus	ESCC	5.18e-66	1.23e+00	0.1177
4791	NFKB2	P4T-E	Human	Esophagus	ESCC	6.07e-21	3.98e-01	0.1323
4791	NFKB2	P5T-E	Human	Esophagus	ESCC	1.22e-17	3.79e-01	0.1327
4791	NFKB2	P8T-E	Human	Esophagus	ESCC	1.25e-19	4.04e-01	0.0889
4791	NFKB2	P9T-E	Human	Esophagus	ESCC	6.56e-10	1.99e-01	0.1131
4791	NFKB2	P11T-E	Human	Esophagus	ESCC	2.02e-17	6.95e-01	0.1426
4791	NFKB2	P12T-E	Human	Esophagus	ESCC	3.30e-11	2.70e-01	0.1122
4791	NFKB2	P15T-E	Human	Esophagus	ESCC	6.09e-12	3.33e-01	0.1149
4791	NFKB2	P16T-E	Human	Esophagus	ESCC	1.50e-31	6.14e-01	0.1153
4791	NFKB2	P17T-E	Human	Esophagus	ESCC	3.81e-14	6.75e-01	0.1278

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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
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
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
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:000756820	Esophagus	ESCC	aging	201/8552	339/18723	2.64e-07	3.94e-06	201
GO:00301984	Esophagus	ESCC	extracellular matrix organization	171/8552	301/18723	6.08e-05	4.67e-04	171
GO:00430624	Esophagus	ESCC	extracellular structure organization	171/8552	302/18723	7.73e-05	5.76e-04	171
GO:00452294	Esophagus	ESCC	external encapsulating structure organization	172/8552	304/18723	7.80e-05	5.80e-04	172
GO:003249619	Esophagus	ESCC	response to lipopolysaccharide	191/8552	343/18723	1.11e-04	7.73e-04	191
GO:004851118	Esophagus	ESCC	rhythmic process	164/8552	298/18723	6.80e-04	3.57e-03	164
GO:000223719	Esophagus	ESCC	response to molecule of bacterial origin	194/8552	363/18723	1.64e-03	7.61e-03	194
GO:0002467	Esophagus	ESCC	germinal center formation	12/8552	14/18723	2.51e-03	1.08e-02	12
GO:00380615	Esophagus	ESCC	NIK/NF-kappaB signaling	81/8552	143/18723	5.33e-03	2.00e-02	81
GO:000756812	Liver	Cirrhotic	aging	117/4634	339/18723	3.13e-05	3.91e-04	117
GO:004851111	Liver	Cirrhotic	rhythmic process	103/4634	298/18723	8.47e-05	9.19e-04	103
GO:0038061	Liver	Cirrhotic	NIK/NF-kappaB signaling	54/4634	143/18723	3.64e-04	3.07e-03	54
GO:00324966	Liver	Cirrhotic	response to lipopolysaccharide	111/4634	343/18723	8.15e-04	5.95e-03	111
GO:00022376	Liver	Cirrhotic	response to molecule of bacterial origin	113/4634	363/18723	3.23e-03	1.81e-02	113
GO:000756822	Liver	HCC	aging	185/7958	339/18723	4.28e-06	5.50e-05	185
GO:004851121	Liver	HCC	rhythmic process	156/7958	298/18723	3.54e-04	2.46e-03	156
GO:003249611	Liver	HCC	response to lipopolysaccharide	174/7958	343/18723	1.19e-03	6.62e-03	174
GO:000223711	Liver	HCC	response to molecule of bacterial origin	181/7958	363/18723	2.58e-03	1.24e-02	181
GO:00380611	Liver	HCC	NIK/NF-kappaB signaling	77/7958	143/18723	3.98e-03	1.76e-02	77
GO:000756818	Oral cavity	OSCC	aging	194/7305	339/18723	6.18e-12	2.33e-10	194

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
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
hsa0520325	Esophagus	ESCC	Viral carcinogenesis	137/4205	204/8465	2.47e-07	1.88e-06	9.62e-07	137
hsa046259	Esophagus	ESCC	C-type lectin receptor signaling pathway	73/4205	104/8465	1.57e-05	7.98e-05	4.09e-05	73
hsa0513428	Esophagus	ESCC	Legionellosis	42/4205	57/8465	1.83e-04	6.90e-04	3.53e-04	42
hsa040645	Esophagus	ESCC	NF-kappa B signaling pathway	67/4205	104/8465	1.62e-03	4.89e-03	2.50e-03	67
hsa05166310	Esophagus	ESCC	Human T-cell leukemia virus 1 infection	164/4205	222/8465	8.13e-14	2.09e-12	1.07e-12	164
hsa0516937	Esophagus	ESCC	Epstein-Barr virus infection	151/4205	202/8465	1.55e-13	3.45e-12	1.77e-12	151
hsa0520335	Esophagus	ESCC	Viral carcinogenesis	137/4205	204/8465	2.47e-07	1.88e-06	9.62e-07	137
hsa0462513	Esophagus	ESCC	C-type lectin receptor signaling pathway	73/4205	104/8465	1.57e-05	7.98e-05	4.09e-05	73
hsa0513436	Esophagus	ESCC	Legionellosis	42/4205	57/8465	1.83e-04	6.90e-04	3.53e-04	42
hsa0406412	Esophagus	ESCC	NF-kappa B signaling pathway	67/4205	104/8465	1.62e-03	4.89e-03	2.50e-03	67
hsa0516614	Liver	Cirrhotic	Human T-cell leukemia virus 1 infection	87/2530	222/8465	1.69e-03	8.01e-03	4.94e-03	87
hsa0513412	Liver	Cirrhotic	Legionellosis	28/2530	57/8465	1.71e-03	8.01e-03	4.94e-03	28
hsa0516914	Liver	Cirrhotic	Epstein-Barr virus infection	80/2530	202/8465	1.80e-03	8.33e-03	5.13e-03	80
hsa05203	Liver	Cirrhotic	Viral carcinogenesis	76/2530	204/8465	1.34e-02	4.20e-02	2.59e-02	76
hsa0516615	Liver	Cirrhotic	Human T-cell leukemia virus 1 infection	87/2530	222/8465	1.69e-03	8.01e-03	4.94e-03	87
hsa0513413	Liver	Cirrhotic	Legionellosis	28/2530	57/8465	1.71e-03	8.01e-03	4.94e-03	28
hsa0516915	Liver	Cirrhotic	Epstein-Barr virus infection	80/2530	202/8465	1.80e-03	8.33e-03	5.13e-03	80
hsa052031	Liver	Cirrhotic	Viral carcinogenesis	76/2530	204/8465	1.34e-02	4.20e-02	2.59e-02	76

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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
NFKB2	SSC	Colorectum	Healthy	MBD4,RELB,C3orf52, etc.	9.29e-02
NFKB2	IMENT	Colorectum	MSS	RELB,CCL20,SOCS3, etc.	4.52e-02
NFKB2	SURF	Endometrium	EEC	TNFAIP2,CSF3,IFNAR2, etc.	3.80e-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

NFKB2

SNV

Missense_Mutation

novel

c.919N>A

p.Leu307Met

p.L307M

Q00653

protein_coding

deleterious(0.01)

probably_damaging(0.999)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NFKB2

SNV

Missense_Mutation

c.419A>G

p.His140Arg

p.H140R

Q00653

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

NFKB2

SNV

Missense_Mutation

novel

c.146N>A

p.Arg49Lys

p.R49K

Q00653

protein_coding

deleterious(0.01)

possibly_damaging(0.722)

TCGA-B6-A0WZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

NFKB2

SNV

Missense_Mutation

c.830N>T

p.Ser277Phe

p.S277F

Q00653

protein_coding

deleterious(0)

probably_damaging(0.959)

TCGA-BH-A0DE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

NFKB2

SNV

Missense_Mutation

rs775379081

c.479N>A

p.Arg160His

p.R160H

Q00653

protein_coding

deleterious(0.01)

probably_damaging(0.969)

TCGA-C8-A8HR-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

5-fluorouracil

NFKB2

SNV

Missense_Mutation

rs767315544

c.1773N>T

p.Gln591His

p.Q591H

Q00653

protein_coding

tolerated(0.67)

benign(0.006)

TCGA-E2-A1IN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

NFKB2

insertion

Frame_Shift_Ins

novel

c.771_772insTGCTTGCTTTCATGGTT

p.Ile258CysfsTer46

p.I258Cfs*46

Q00653

protein_coding

TCGA-A7-A0CJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

NFKB2

deletion

Frame_Shift_Del

c.879delC

p.Tyr294IlefsTer4

p.Y294Ifs*4

Q00653

protein_coding

TCGA-A7-A0DA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

NFKB2

insertion

Frame_Shift_Ins

novel

c.1015_1016insCAAGCTGTGCAGTCAAACA

p.Arg339ProfsTer173

p.R339Pfs*173

Q00653

protein_coding

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

NFKB2

SNV

Missense_Mutation

novel

c.65C>A

p.Ser22Tyr

p.S22Y

Q00653

protein_coding

tolerated(0.05)

benign(0.084)

TCGA-2W-A8YY-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
4791	NFKB2	CLINICALLY ACTIONABLE, DRUGGABLE GENOME, KINASE, TRANSCRIPTION FACTOR		Quinoxaline derivative 3
4791	NFKB2	CLINICALLY ACTIONABLE, DRUGGABLE GENOME, KINASE, TRANSCRIPTION FACTOR		1-hydroxyl-3,5-bis(4-hydroxylstyryl)benzene derivative 1
4791	NFKB2	CLINICALLY ACTIONABLE, DRUGGABLE GENOME, KINASE, TRANSCRIPTION FACTOR		MD1003
4791	NFKB2	CLINICALLY ACTIONABLE, DRUGGABLE GENOME, KINASE, TRANSCRIPTION FACTOR		PG-490-88
4791	NFKB2	CLINICALLY ACTIONABLE, DRUGGABLE GENOME, KINASE, TRANSCRIPTION FACTOR		PMID25553724-Compound-US20138552206 5
4791	NFKB2	CLINICALLY ACTIONABLE, DRUGGABLE GENOME, KINASE, TRANSCRIPTION FACTOR		CID 867101	CHEMBL406557
4791	NFKB2	CLINICALLY ACTIONABLE, DRUGGABLE GENOME, KINASE, TRANSCRIPTION FACTOR		Edasalonexent	EDASALONEXENT
4791	NFKB2	CLINICALLY ACTIONABLE, DRUGGABLE GENOME, KINASE, TRANSCRIPTION FACTOR		PMID25553724-Compound-US2011801300410
4791	NFKB2	CLINICALLY ACTIONABLE, DRUGGABLE GENOME, KINASE, TRANSCRIPTION FACTOR		N-quinolin-benzene sulphonamide derivative 1
4791	NFKB2	CLINICALLY ACTIONABLE, DRUGGABLE GENOME, KINASE, TRANSCRIPTION FACTOR		DNDI1417548	CHEMBL2094789

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