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: RELA

Gene summary for RELA

Gene summary.

Gene information	Species	Human
	Gene symbol	RELA
	Gene ID	5970
	Gene name	RELA proto-oncogene, NF-kB subunit
	Gene Alias	CMCU
	Cytomap	11q13.1
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	Q04206

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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
5970	RELA	LZE4T	Human	Esophagus	ESCC	1.86e-06	1.55e-01	0.0811
5970	RELA	LZE5T	Human	Esophagus	ESCC	1.55e-02	-1.34e-02	0.0514
5970	RELA	LZE7T	Human	Esophagus	ESCC	1.61e-11	1.22e-01	0.0667
5970	RELA	LZE8T	Human	Esophagus	ESCC	2.43e-15	3.08e-01	0.067
5970	RELA	LZE20T	Human	Esophagus	ESCC	5.32e-06	6.17e-01	0.0662
5970	RELA	LZE24T	Human	Esophagus	ESCC	4.89e-18	8.60e-01	0.0596
5970	RELA	LZE21T	Human	Esophagus	ESCC	2.75e-03	1.76e-01	0.0655
5970	RELA	LZE6T	Human	Esophagus	ESCC	1.47e-05	1.97e-01	0.0845
5970	RELA	P1T-E	Human	Esophagus	ESCC	8.47e-05	6.73e-01	0.0875
5970	RELA	P2T-E	Human	Esophagus	ESCC	1.35e-19	3.18e-01	0.1177
5970	RELA	P4T-E	Human	Esophagus	ESCC	2.61e-18	5.10e-01	0.1323
5970	RELA	P5T-E	Human	Esophagus	ESCC	8.97e-14	3.87e-01	0.1327
5970	RELA	P8T-E	Human	Esophagus	ESCC	1.09e-26	6.45e-01	0.0889
5970	RELA	P9T-E	Human	Esophagus	ESCC	5.91e-12	2.12e-01	0.1131
5970	RELA	P10T-E	Human	Esophagus	ESCC	7.62e-29	6.07e-01	0.116
5970	RELA	P11T-E	Human	Esophagus	ESCC	3.64e-11	4.84e-01	0.1426
5970	RELA	P12T-E	Human	Esophagus	ESCC	2.35e-14	2.53e-01	0.1122
5970	RELA	P15T-E	Human	Esophagus	ESCC	9.30e-16	4.96e-01	0.1149
5970	RELA	P16T-E	Human	Esophagus	ESCC	4.15e-16	2.99e-01	0.1153
5970	RELA	P17T-E	Human	Esophagus	ESCC	3.00e-05	4.32e-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
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ

∗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:190165317	Oral cavity	LP	cellular response to peptide	122/4623	359/18723	4.22e-05	6.10e-04	122
GO:004358816	Oral cavity	LP	skin development	93/4623	263/18723	6.47e-05	8.70e-04	93
GO:004206313	Oral cavity	LP	gliogenesis	104/4623	301/18723	7.21e-05	9.49e-04	104
GO:000758414	Oral cavity	LP	response to nutrient	65/4623	174/18723	1.31e-04	1.52e-03	65
GO:007030115	Oral cavity	LP	cellular response to hydrogen peroxide	40/4623	98/18723	3.12e-04	3.17e-03	40
GO:190122212	Oral cavity	LP	regulation of NIK/NF-kappaB signaling	44/4623	112/18723	4.38e-04	4.19e-03	44
GO:001000111	Oral cavity	LP	glial cell differentiation	78/4623	225/18723	4.82e-04	4.52e-03	78
GO:003249618	Oral cavity	LP	response to lipopolysaccharide	112/4623	343/18723	4.90e-04	4.60e-03	112
GO:007121616	Oral cavity	LP	cellular response to biotic stimulus	84/4623	246/18723	5.17e-04	4.82e-03	84
GO:001692511	Oral cavity	LP	protein sumoylation	24/4623	53/18723	8.55e-04	7.45e-03	24
GO:003327311	Oral cavity	LP	response to vitamin	37/4623	93/18723	9.14e-04	7.79e-03	37
GO:003286817	Oral cavity	LP	response to insulin	88/4623	264/18723	9.19e-04	7.82e-03	88
GO:003286917	Oral cavity	LP	cellular response to insulin stimulus	70/4623	203/18723	1.07e-03	8.96e-03	70
GO:2001237110	Oral cavity	LP	negative regulation of extrinsic apoptotic signaling pathway	38/4623	97/18723	1.11e-03	9.13e-03	38
GO:007137515	Oral cavity	LP	cellular response to peptide hormone stimulus	95/4623	290/18723	1.12e-03	9.19e-03	95
GO:190122413	Oral cavity	LP	positive regulation of NIK/NF-kappaB signaling	29/4623	69/18723	1.15e-03	9.40e-03	29
GO:000608114	Oral cavity	LP	cellular aldehyde metabolic process	26/4623	60/18723	1.19e-03	9.62e-03	26
GO:003806112	Oral cavity	LP	NIK/NF-kappaB signaling	52/4623	143/18723	1.20e-03	9.66e-03	52
GO:005109114	Oral cavity	LP	positive regulation of DNA-binding transcription factor activity	86/4623	260/18723	1.35e-03	1.08e-02	86
GO:000223718	Oral cavity	LP	response to molecule of bacterial origin	115/4623	363/18723	1.42e-03	1.13e-02	115

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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
hsa05022210	Esophagus	ESCC	Pathways of neurodegeneration - multiple diseases	318/4205	476/8465	6.10e-15	2.04e-13	1.05e-13	318
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
hsa0421829	Esophagus	ESCC	Cellular senescence	119/4205	156/8465	5.89e-12	9.40e-11	4.81e-11	119
hsa05415211	Esophagus	ESCC	Diabetic cardiomyopathy	146/4205	203/8465	5.81e-11	7.78e-10	3.99e-10	146
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

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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
RELA	CD8TCM	Lung	IAC	RNASE1,LYPD3,CASZ1, etc.	3.85e-02

∗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

RELA

SNV

Missense_Mutation

rs568782744

c.496N>T

p.Arg166Trp

p.R166W

Q04206

protein_coding

tolerated(0.12)

possibly_damaging(0.666)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RELA

insertion

Frame_Shift_Ins

novel

c.1395_1396insGG

p.Leu466GlyfsTer14

p.L466Gfs*14

Q04206

protein_coding

TCGA-A2-A04Y-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

RELA

insertion

In_Frame_Ins

novel

c.1394_1395insGGTCTCTGC

p.Asp465delinsGluValSerAla

p.D465delinsEVSA

Q04206

protein_coding

TCGA-A2-A04Y-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

RELA

SNV

Missense_Mutation

rs750564559

c.398N>A

p.Arg133His

p.R133H

Q04206

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

RELA

SNV

Missense_Mutation

c.115N>A

p.Glu39Lys

p.E39K

Q04206

protein_coding

deleterious(0)

probably_damaging(0.992)

TCGA-EK-A3GK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

RELA

SNV

Missense_Mutation

c.1313N>T

p.Glu438Val

p.E438V

Q04206

protein_coding

deleterious(0.01)

probably_damaging(0.95)

TCGA-Q1-A73O-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

RELA

SNV

Missense_Mutation

c.1312N>C

p.Glu438Gln

p.E438Q

Q04206

protein_coding

tolerated(0.06)

probably_damaging(0.932)

TCGA-Q1-A73O-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

RELA

SNV

Missense_Mutation

c.379N>A

p.Glu127Lys

p.E127K

Q04206

protein_coding

tolerated(0.69)

possibly_damaging(0.467)

TCGA-VS-A9V3-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

RELA

SNV

Missense_Mutation

c.1450N>A

p.Val484Met

p.V484M

Q04206

protein_coding

tolerated_low_confidence(0.13)

benign(0)

TCGA-AA-3511-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

RELA

SNV

Missense_Mutation

c.559N>T

p.Arg187Cys

p.R187C

Q04206

protein_coding

deleterious(0)

probably_damaging(0.989)

TCGA-AA-3821-01

Colorectum

colon adenocarcinoma

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
5970	RELA	DRUGGABLE GENOME, CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR, KINASE, TRANSCRIPTION FACTOR COMPLEX		PYROGALLOL RED	PYROGALLOL RED	16759101
5970	RELA	DRUGGABLE GENOME, CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR, KINASE, TRANSCRIPTION FACTOR COMPLEX		ACACETIN	ACACETIN	25190466
5970	RELA	DRUGGABLE GENOME, CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR, KINASE, TRANSCRIPTION FACTOR COMPLEX		ANTISENSE OLIGONUCLEOTIDES		8035811
5970	RELA	DRUGGABLE GENOME, CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR, KINASE, TRANSCRIPTION FACTOR COMPLEX		2-PHENYLACETYLAMINOBENZOTHIAZOLE	CHEMBL1405979
5970	RELA	DRUGGABLE GENOME, CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR, KINASE, TRANSCRIPTION FACTOR COMPLEX		PYRROLIDINE DITHIOCARBAMATE	PYRROLIDINE DITHIOCARBAMATE
5970	RELA	DRUGGABLE GENOME, CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR, KINASE, TRANSCRIPTION FACTOR COMPLEX		ISOLIQUIRITIGENIN	ISOLIQUIRITIGENIN	21866899
5970	RELA	DRUGGABLE GENOME, CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR, KINASE, TRANSCRIPTION FACTOR COMPLEX		APIGENIN	APIGENIN	25190466
5970	RELA	DRUGGABLE GENOME, CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR, KINASE, TRANSCRIPTION FACTOR COMPLEX		CID 739615	CHEMBL260560
5970	RELA	DRUGGABLE GENOME, CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR, KINASE, TRANSCRIPTION FACTOR COMPLEX		4',7-DIMETHOXY-5-HYDROXYGENISTEIN	4',7-DIMETHOXY-5-HYDROXYGENISTEIN
5970	RELA	DRUGGABLE GENOME, CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR, KINASE, TRANSCRIPTION FACTOR COMPLEX		PARTHENOLIDE	PARTHENOLIDE	25190466

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