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: RELB

Gene summary for RELB

Gene summary.

Gene information	Species	Human
	Gene symbol	RELB
	Gene ID	5971
	Gene name	RELB proto-oncogene, NF-kB subunit
	Gene Alias	I-REL
	Cytomap	19q13.32
	Gene Type	protein-coding
	GO ID	GO:0001773
	UniProtAcc	Q01201

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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
5971	RELB	LZE4T	Human	Esophagus	ESCC	4.57e-07	2.16e-01	0.0811
5971	RELB	LZE8T	Human	Esophagus	ESCC	4.57e-02	4.96e-02	0.067
5971	RELB	LZE20T	Human	Esophagus	ESCC	1.34e-09	2.39e-01	0.0662
5971	RELB	LZE22T	Human	Esophagus	ESCC	5.88e-09	8.46e-01	0.068
5971	RELB	LZE24T	Human	Esophagus	ESCC	9.79e-22	7.05e-01	0.0596
5971	RELB	LZE21T	Human	Esophagus	ESCC	3.25e-06	3.86e-01	0.0655
5971	RELB	P1T-E	Human	Esophagus	ESCC	1.73e-23	1.25e+00	0.0875
5971	RELB	P2T-E	Human	Esophagus	ESCC	6.11e-76	1.58e+00	0.1177
5971	RELB	P4T-E	Human	Esophagus	ESCC	3.83e-60	1.30e+00	0.1323
5971	RELB	P5T-E	Human	Esophagus	ESCC	2.84e-53	1.20e+00	0.1327
5971	RELB	P8T-E	Human	Esophagus	ESCC	2.49e-48	1.43e+00	0.0889
5971	RELB	P9T-E	Human	Esophagus	ESCC	3.52e-19	5.29e-01	0.1131
5971	RELB	P10T-E	Human	Esophagus	ESCC	7.04e-31	1.02e+00	0.116
5971	RELB	P11T-E	Human	Esophagus	ESCC	1.11e-26	9.17e-01	0.1426
5971	RELB	P12T-E	Human	Esophagus	ESCC	7.02e-20	5.69e-01	0.1122
5971	RELB	P15T-E	Human	Esophagus	ESCC	6.66e-28	7.43e-01	0.1149
5971	RELB	P16T-E	Human	Esophagus	ESCC	3.67e-39	8.24e-01	0.1153
5971	RELB	P17T-E	Human	Esophagus	ESCC	5.36e-18	7.61e-01	0.1278
5971	RELB	P19T-E	Human	Esophagus	ESCC	6.90e-15	1.01e+00	0.1662
5971	RELB	P20T-E	Human	Esophagus	ESCC	2.68e-32	9.20e-01	0.1124

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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
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
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:003247911	Oral cavity	EOLP	regulation of type I interferon production	27/2218	95/18723	9.68e-06	1.75e-04	27
GO:003260611	Oral cavity	EOLP	type I interferon production	27/2218	95/18723	9.68e-06	1.75e-04	27
GO:00326081	Oral cavity	EOLP	interferon-beta production	19/2218	56/18723	1.27e-05	2.15e-04	19
GO:00326481	Oral cavity	EOLP	regulation of interferon-beta production	19/2218	56/18723	1.27e-05	2.15e-04	19
GO:0043367	Oral cavity	EOLP	CD4-positive, alpha-beta T cell differentiation	24/2218	83/18723	2.17e-05	3.35e-04	24
GO:00022633	Oral cavity	EOLP	cell activation involved in immune response	56/2218	279/18723	4.91e-05	6.47e-04	56
GO:000762317	Oral cavity	EOLP	circadian rhythm	45/2218	210/18723	5.24e-05	6.79e-04	45
GO:00023662	Oral cavity	EOLP	leukocyte activation involved in immune response	55/2218	275/18723	6.32e-05	7.90e-04	55
GO:00022852	Oral cavity	EOLP	lymphocyte activation involved in immune response	42/2218	194/18723	7.17e-05	8.82e-04	42
GO:003292221	Oral cavity	EOLP	circadian regulation of gene expression	20/2218	68/18723	7.88e-05	9.51e-04	20
GO:006219726	Oral cavity	EOLP	cellular response to chemical stress	64/2218	337/18723	8.49e-05	1.01e-03	64
GO:003806121	Oral cavity	EOLP	NIK/NF-kappaB signaling	32/2218	143/18723	2.64e-04	2.56e-03	32
GO:0042093	Oral cavity	EOLP	T-helper cell differentiation	18/2218	66/18723	4.94e-04	4.31e-03	18
GO:00022864	Oral cavity	EOLP	T cell activation involved in immune response	26/2218	114/18723	7.06e-04	5.78e-03	26
GO:0002294	Oral cavity	EOLP	CD4-positive, alpha-beta T cell differentiation involved in immune response	18/2218	68/18723	7.29e-04	5.94e-03	18
GO:0002287	Oral cavity	EOLP	alpha-beta T cell activation involved in immune response	18/2218	69/18723	8.79e-04	6.75e-03	18
GO:0002293	Oral cavity	EOLP	alpha-beta T cell differentiation involved in immune response	18/2218	69/18723	8.79e-04	6.75e-03	18
GO:0002292	Oral cavity	EOLP	T cell differentiation involved in immune response	19/2218	75/18723	9.43e-04	7.15e-03	19
GO:0045063	Oral cavity	EOLP	T-helper 1 cell differentiation	7/2218	20/18723	6.20e-03	3.09e-02	7
GO:0032480	Oral cavity	EOLP	negative regulation of type I interferon production	9/2218	30/18723	6.33e-03	3.13e-02	9

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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
hsa046259	Esophagus	ESCC	C-type lectin receptor signaling pathway	73/4205	104/8465	1.57e-05	7.98e-05	4.09e-05	73
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
hsa0462513	Esophagus	ESCC	C-type lectin receptor signaling pathway	73/4205	104/8465	1.57e-05	7.98e-05	4.09e-05	73
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
hsa0516914	Liver	Cirrhotic	Epstein-Barr virus infection	80/2530	202/8465	1.80e-03	8.33e-03	5.13e-03	80
hsa0516615	Liver	Cirrhotic	Human T-cell leukemia virus 1 infection	87/2530	222/8465	1.69e-03	8.01e-03	4.94e-03	87
hsa0516915	Liver	Cirrhotic	Epstein-Barr virus infection	80/2530	202/8465	1.80e-03	8.33e-03	5.13e-03	80
hsa0516921	Liver	HCC	Epstein-Barr virus infection	128/4020	202/8465	3.17e-06	2.79e-05	1.55e-05	128
hsa0516622	Liver	HCC	Human T-cell leukemia virus 1 infection	139/4020	222/8465	3.17e-06	2.79e-05	1.55e-05	139
hsa0516931	Liver	HCC	Epstein-Barr virus infection	128/4020	202/8465	3.17e-06	2.79e-05	1.55e-05	128
hsa0516632	Liver	HCC	Human T-cell leukemia virus 1 infection	139/4020	222/8465	3.17e-06	2.79e-05	1.55e-05	139
hsa0516616	Lung	IAC	Human T-cell leukemia virus 1 infection	49/1053	222/8465	3.44e-05	6.38e-04	4.24e-04	49
hsa040108	Lung	IAC	MAPK signaling pathway	62/1053	302/8465	3.54e-05	6.38e-04	4.24e-04	62
hsa04625	Lung	IAC	C-type lectin receptor signaling pathway	26/1053	104/8465	3.15e-04	3.11e-03	2.06e-03	26
hsa0516916	Lung	IAC	Epstein-Barr virus infection	40/1053	202/8465	1.72e-03	9.66e-03	6.41e-03	40

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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
RELB	IMENT	Colorectum	SER	RP11-63A11.1,NFKBIA,SQSTM1, etc.	1.85e-01
RELB	QUIE	Esophagus	Healthy	MMP1,ING1,NTRK2, etc.	6.37e-02
RELB	STM	Oral cavity	NEOLP	NINJ1,ICAM1,BTG1, etc.	8.12e-01
RELB	ECC	Skin	Healthy	LCP1,RAB6A,KRT8, etc.	2.94e-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

RELB

SNV

Missense_Mutation

c.866N>T

p.Ser289Phe

p.S289F

Q01201

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-EW-A1J5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

RELB

insertion

In_Frame_Ins

novel

c.1660_1661insCAAGAGCACGTCATT

p.Gly554delinsAlaArgAlaArgHisCys

p.G554delinsARARHC

Q01201

protein_coding

TCGA-BH-A0AY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

RELB

SNV

Missense_Mutation

novel

c.561N>T

p.Lys187Asn

p.K187N

Q01201

protein_coding

tolerated(0.05)

probably_damaging(0.996)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

RELB

SNV

Missense_Mutation

rs372431384

c.638N>A

p.Arg213Gln

p.R213Q

Q01201

protein_coding

tolerated(0.22)

benign(0.093)

TCGA-C5-A1MH-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

RELB

SNV

Missense_Mutation

novel

c.122N>G

p.Ser41Cys

p.S41C

Q01201

protein_coding

deleterious_low_confidence(0)

benign(0.237)

TCGA-MY-A5BD-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

RELB

SNV

Missense_Mutation

c.1459G>A

p.Asp487Asn

p.D487N

Q01201

protein_coding

deleterious_low_confidence(0.05)

benign(0)

TCGA-AA-3864-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

RELB

SNV

Missense_Mutation

novel

c.920N>A

p.Arg307Gln

p.R307Q

Q01201

protein_coding

deleterious(0.01)

possibly_damaging(0.796)

TCGA-AA-3950-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

RELB

SNV

Missense_Mutation

rs747326911

c.823N>T

p.Arg275Trp

p.R275W

Q01201

protein_coding

deleterious(0.02)

probably_damaging(0.979)

TCGA-AZ-6598-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

RELB

SNV

Missense_Mutation

rs376021184

c.199N>A

p.Gly67Ser

p.G67S

Q01201

protein_coding

deleterious_low_confidence(0.01)

benign(0.04)

TCGA-NH-A5IV-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

RELB

SNV

Missense_Mutation

novel

c.715N>G

p.Ile239Val

p.I239V

Q01201

protein_coding

tolerated(0.09)

benign(0.081)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

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

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