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: RNF40

Gene summary for RNF40

Gene summary.

Gene information	Species	Human
	Gene symbol	RNF40
	Gene ID	9810
	Gene name	ring finger protein 40
	Gene Alias	BRE1B
	Cytomap	16p11.2
	Gene Type	protein-coding
	GO ID	GO:0000209
	UniProtAcc	A8K6K1

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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
9810	RNF40	LZE2T	Human	Esophagus	ESCC	5.07e-03	3.92e-01	0.082
9810	RNF40	LZE4T	Human	Esophagus	ESCC	2.20e-09	1.97e-01	0.0811
9810	RNF40	LZE7T	Human	Esophagus	ESCC	9.74e-10	4.62e-01	0.0667
9810	RNF40	LZE8T	Human	Esophagus	ESCC	2.10e-10	2.83e-01	0.067
9810	RNF40	LZE20T	Human	Esophagus	ESCC	5.29e-04	1.34e-01	0.0662
9810	RNF40	LZE22D1	Human	Esophagus	HGIN	2.88e-02	8.90e-02	0.0595
9810	RNF40	LZE22T	Human	Esophagus	ESCC	2.43e-04	2.62e-01	0.068
9810	RNF40	LZE24T	Human	Esophagus	ESCC	5.49e-35	9.65e-01	0.0596
9810	RNF40	LZE21T	Human	Esophagus	ESCC	5.07e-04	2.70e-01	0.0655
9810	RNF40	LZE6T	Human	Esophagus	ESCC	2.88e-05	1.77e-01	0.0845
9810	RNF40	P1T-E	Human	Esophagus	ESCC	1.44e-16	5.40e-01	0.0875
9810	RNF40	P2T-E	Human	Esophagus	ESCC	4.83e-38	7.07e-01	0.1177
9810	RNF40	P4T-E	Human	Esophagus	ESCC	6.65e-21	4.18e-01	0.1323
9810	RNF40	P5T-E	Human	Esophagus	ESCC	9.89e-16	1.88e-01	0.1327
9810	RNF40	P8T-E	Human	Esophagus	ESCC	6.92e-22	4.55e-01	0.0889
9810	RNF40	P9T-E	Human	Esophagus	ESCC	3.22e-12	2.47e-01	0.1131
9810	RNF40	P10T-E	Human	Esophagus	ESCC	6.13e-16	1.95e-01	0.116
9810	RNF40	P11T-E	Human	Esophagus	ESCC	5.15e-19	6.53e-01	0.1426
9810	RNF40	P12T-E	Human	Esophagus	ESCC	5.30e-34	6.67e-01	0.1122
9810	RNF40	P15T-E	Human	Esophagus	ESCC	1.21e-31	5.18e-01	0.1149

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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
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:190336229	Skin	cSCC	regulation of cellular protein catabolic process	139/4864	255/18723	2.06e-22	4.17e-20	139
GO:190305029	Skin	cSCC	regulation of proteolysis involved in cellular protein catabolic process	121/4864	221/18723	6.75e-20	1.01e-17	121
GO:006113629	Skin	cSCC	regulation of proteasomal protein catabolic process	106/4864	187/18723	4.31e-19	5.87e-17	106
GO:190332029	Skin	cSCC	regulation of protein modification by small protein conjugation or removal	125/4864	242/18723	9.50e-18	1.05e-15	125
GO:004586229	Skin	cSCC	positive regulation of proteolysis	169/4864	372/18723	2.43e-16	2.21e-14	169
GO:000989628	Skin	cSCC	positive regulation of catabolic process	206/4864	492/18723	6.06e-15	4.64e-13	206
GO:003139629	Skin	cSCC	regulation of protein ubiquitination	107/4864	210/18723	7.17e-15	5.35e-13	107
GO:190336429	Skin	cSCC	positive regulation of cellular protein catabolic process	85/4864	155/18723	1.87e-14	1.31e-12	85
GO:003133128	Skin	cSCC	positive regulation of cellular catabolic process	182/4864	427/18723	3.29e-14	2.22e-12	182
GO:004573229	Skin	cSCC	positive regulation of protein catabolic process	112/4864	231/18723	1.37e-13	8.40e-12	112
GO:190180025	Skin	cSCC	positive regulation of proteasomal protein catabolic process	66/4864	114/18723	5.18e-13	3.01e-11	66
GO:190305225	Skin	cSCC	positive regulation of proteolysis involved in cellular protein catabolic process	72/4864	133/18723	4.24e-12	2.27e-10	72
GO:001657024	Skin	cSCC	histone modification	179/4864	463/18723	9.65e-10	3.74e-08	179
GO:000020924	Skin	cSCC	protein polyubiquitination	103/4864	236/18723	2.57e-09	9.09e-08	103
GO:00311234	Skin	cSCC	RNA 3'-end processing	58/4864	116/18723	2.47e-08	6.89e-07	58
GO:005068617	Skin	cSCC	negative regulation of mRNA processing	22/4864	29/18723	2.73e-08	7.41e-07	22
GO:190332217	Skin	cSCC	positive regulation of protein modification by small protein conjugation or removal	64/4864	138/18723	1.79e-07	3.94e-06	64
GO:190331228	Skin	cSCC	negative regulation of mRNA metabolic process	47/4864	92/18723	2.24e-07	4.77e-06	47
GO:003105615	Skin	cSCC	regulation of histone modification	68/4864	152/18723	4.07e-07	7.93e-06	68
GO:00311244	Skin	cSCC	mRNA 3'-end processing	34/4864	62/18723	1.27e-06	2.20e-05	34

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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

Cell Type

Tissue

Disease Stage

Target Gene

RSS

Regulon Activity

∗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

RNF40

SNV

Missense_Mutation

c.2281A>G

p.Thr761Ala

p.T761A

O75150

protein_coding

deleterious(0)

probably_damaging(0.954)

TCGA-A2-A0YE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Taxotere

RNF40

SNV

Missense_Mutation

c.1547G>T

p.Gly516Val

p.G516V

O75150

protein_coding

tolerated(0.37)

benign(0.202)

TCGA-A2-A25A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Cytoxan

RNF40

SNV

Missense_Mutation

c.589N>C

p.Glu197Gln

p.E197Q

O75150

protein_coding

tolerated(0.9)

possibly_damaging(0.73)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RNF40

SNV

Missense_Mutation

rs751674221

c.179N>G

p.Ala60Gly

p.A60G

O75150

protein_coding

tolerated(0.21)

benign(0.373)

TCGA-AC-A3OD-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RNF40

SNV

Missense_Mutation

c.1409N>A

p.Leu470Gln

p.L470Q

O75150

protein_coding

deleterious(0.05)

probably_damaging(0.999)

TCGA-BH-A208-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

RNF40

SNV

Missense_Mutation

c.1330N>C

p.Glu444Gln

p.E444Q

O75150

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-C8-A26Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RNF40

SNV

Missense_Mutation

c.2390N>G

p.Asn797Ser

p.N797S

O75150

protein_coding

deleterious(0)

probably_damaging(0.954)

TCGA-GM-A2DF-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxol

RNF40

insertion

In_Frame_Ins

novel

c.1599_1600insATTGGATGTATAAAAAAAAAAAAGAAAAAA

p.Gly533_His534insIleGlyCysIleLysLysLysLysLysLys

p.G533_H534insIGCIKKKKKK

O75150

protein_coding

TCGA-A8-A06O-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

letrozole

RNF40

insertion

In_Frame_Ins

novel

c.2947_2948insCTTGTCCTTTTGAGGGGACACATGATA

p.Cys983delinsSerCysProPheGluGlyThrHisAspSer

p.C983delinsSCPFEGTHDS

O75150

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RNF40

insertion

Nonsense_Mutation

novel

c.355_356insGACGGGGGCTCAGGGCCCC

p.Ser119Ter

p.S119*

O75150

protein_coding

TCGA-AO-A03L-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

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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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