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:003466012	Esophagus	ESCC	ncRNA metabolic process	346/8552	485/18723	4.35e-31	2.51e-28	346
GO:0042176111	Esophagus	ESCC	regulation of protein catabolic process	280/8552	391/18723	8.65e-26	2.39e-23	280
GO:2001233111	Esophagus	ESCC	regulation of apoptotic signaling pathway	256/8552	356/18723	4.11e-24	1.04e-21	256
GO:0006979111	Esophagus	ESCC	response to oxidative stress	303/8552	446/18723	7.15e-22	1.30e-19	303
GO:1903320111	Esophagus	ESCC	regulation of protein modification by small protein conjugation or removal	181/8552	242/18723	1.80e-20	2.60e-18	181
GO:001820514	Esophagus	ESCC	peptidyl-lysine modification	259/8552	376/18723	3.90e-20	5.26e-18	259
GO:0062197111	Esophagus	ESCC	cellular response to chemical stress	234/8552	337/18723	5.37e-19	5.97e-17	234
GO:0097191111	Esophagus	ESCC	extrinsic apoptotic signaling pathway	159/8552	219/18723	4.12e-16	2.94e-14	159
GO:2001234111	Esophagus	ESCC	negative regulation of apoptotic signaling pathway	161/8552	224/18723	1.24e-15	8.09e-14	161
GO:000941113	Esophagus	ESCC	response to UV	115/8552	149/18723	3.29e-15	1.93e-13	115
GO:0034250111	Esophagus	ESCC	positive regulation of cellular amide metabolic process	123/8552	162/18723	3.32e-15	1.93e-13	123
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:2001236111	Esophagus	ESCC	regulation of extrinsic apoptotic signaling pathway	111/8552	151/18723	2.97e-12	1.18e-10	111
GO:0043122110	Esophagus	ESCC	regulation of I-kappaB kinase/NF-kappaB signaling	167/8552	249/18723	6.11e-12	2.32e-10	167
GO:0048732111	Esophagus	ESCC	gland development	269/8552	436/18723	7.81e-12	2.95e-10	269
GO:0031667111	Esophagus	ESCC	response to nutrient levels	289/8552	474/18723	9.25e-12	3.47e-10	289
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

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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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