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: EDA

Gene summary for EDA

Gene summary.

Gene information	Species	Human
	Gene symbol	EDA
	Gene ID	1896
	Gene name	ectodysplasin A
	Gene Alias	ECTD1
	Cytomap	Xq13.1
	Gene Type	protein-coding
	GO ID	GO:0001942
	UniProtAcc	A0A0U5J797

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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
1896	EDA	AEH-subject1	Human	Endometrium	AEH	6.18e-04	2.48e-01	-0.3059
1896	EDA	AEH-subject3	Human	Endometrium	AEH	4.32e-03	2.61e-01	-0.2576
1896	EDA	AEH-subject4	Human	Endometrium	AEH	2.39e-02	2.77e-01	-0.2657
1896	EDA	AEH-subject5	Human	Endometrium	AEH	7.79e-14	5.19e-01	-0.2953
1896	EDA	EEC-subject1	Human	Endometrium	EEC	1.54e-09	4.12e-01	-0.2682
1896	EDA	EEC-subject4	Human	Endometrium	EEC	1.30e-20	6.33e-01	-0.2571

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Endometrium		AEH: Atypical endometrial hyperplasia
Endometrium		EEC: Endometrioid 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:00423033	Esophagus	ESCC	molting cycle	64/8552	107/18723	2.24e-03	9.85e-03	64
GO:00426333	Esophagus	ESCC	hair cycle	64/8552	107/18723	2.24e-03	9.85e-03	64
GO:00434731	Esophagus	ESCC	pigmentation	59/8552	98/18723	2.64e-03	1.12e-02	59
GO:00703046	Esophagus	ESCC	positive regulation of stress-activated protein kinase signaling cascade	74/8552	128/18723	3.77e-03	1.53e-02	74
GO:00380615	Esophagus	ESCC	NIK/NF-kappaB signaling	81/8552	143/18723	5.33e-03	2.00e-02	81
GO:00328745	Esophagus	ESCC	positive regulation of stress-activated MAPK cascade	72/8552	126/18723	6.24e-03	2.29e-02	72
GO:00463302	Esophagus	ESCC	positive regulation of JNK cascade	52/8552	89/18723	1.04e-02	3.56e-02	52
GO:00454448	Oral cavity	OSCC	fat cell differentiation	120/7305	229/18723	2.48e-05	2.32e-04	120
GO:00455983	Oral cavity	OSCC	regulation of fat cell differentiation	77/7305	139/18723	6.36e-05	5.18e-04	77
GO:00380614	Oral cavity	OSCC	NIK/NF-kappaB signaling	78/7305	143/18723	1.14e-04	8.35e-04	78
GO:00456006	Oral cavity	OSCC	positive regulation of fat cell differentiation	41/7305	66/18723	1.20e-04	8.60e-04	41
GO:19012246	Oral cavity	OSCC	positive regulation of NIK/NF-kappaB signaling	40/7305	69/18723	1.08e-03	5.56e-03	40
GO:19012224	Oral cavity	OSCC	regulation of NIK/NF-kappaB signaling	59/7305	112/18723	2.25e-03	1.00e-02	59
GO:190122212	Oral cavity	LP	regulation of NIK/NF-kappaB signaling	44/4623	112/18723	4.38e-04	4.19e-03	44
GO:190122413	Oral cavity	LP	positive regulation of NIK/NF-kappaB signaling	29/4623	69/18723	1.15e-03	9.40e-03	29
GO:003806112	Oral cavity	LP	NIK/NF-kappaB signaling	52/4623	143/18723	1.20e-03	9.66e-03	52
GO:004560022	Oral cavity	NEOLP	positive regulation of fat cell differentiation	24/2005	66/18723	3.20e-08	1.35e-06	24
GO:004559821	Oral cavity	NEOLP	regulation of fat cell differentiation	37/2005	139/18723	1.12e-07	4.05e-06	37
GO:004544422	Oral cavity	NEOLP	fat cell differentiation	50/2005	229/18723	6.79e-07	1.93e-05	50

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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
EDA	EDAR	EDA_EDAR	EDA	Cervix	CC

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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

EDA

SNV

Missense_Mutation

novel

c.550C>A

p.Pro184Thr

p.P184T

Q92838

protein_coding

tolerated_low_confidence(0.14)

probably_damaging(0.998)

TCGA-A2-A04R-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxol

EDA

SNV

Missense_Mutation

c.408G>T

p.Leu136Phe

p.L136F

Q92838

protein_coding

deleterious_low_confidence(0.01)

benign(0.047)

TCGA-A8-A08F-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

5-fluorouracil

EDA

SNV

Missense_Mutation

rs132630312

c.463C>T

p.Arg155Cys

p.R155C

Q92838

protein_coding

deleterious_low_confidence(0)

benign(0)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

EDA

SNV

Missense_Mutation

c.353N>T

p.Pro118Leu

p.P118L

Q92838

protein_coding

tolerated_low_confidence(0.1)

benign(0)

TCGA-DS-A1OC-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

gemcitabine

EDA

SNV

Missense_Mutation

novel

c.116N>A

p.Ser39Asn

p.S39N

Q92838

protein_coding

tolerated_low_confidence(0.19)

benign(0.003)

TCGA-EA-A439-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

EDA

SNV

Missense_Mutation

novel

c.397N>G

p.Met133Val

p.M133V

Q92838

protein_coding

tolerated_low_confidence(0.4)

benign(0)

TCGA-ZJ-AAXJ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

EDA

SNV

Missense_Mutation

c.796N>A

p.Leu266Ile

p.L266I

Q92838

protein_coding

deleterious_low_confidence(0.02)

probably_damaging(0.979)

TCGA-AA-3977-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

EDA

SNV

Missense_Mutation

c.929N>G

p.Tyr310Cys

p.Y310C

Q92838

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.995)

TCGA-D5-6927-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

EDA

SNV

Missense_Mutation

novel

c.476N>T

p.Arg159Ile

p.R159I

Q92838

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.944)

TCGA-AG-3892-01

Colorectum

rectum adenocarcinoma

Female

<65

I/II

Unknown

EDA

SNV

Missense_Mutation

c.497C>T

p.Ala166Val

p.A166V

Q92838

protein_coding

tolerated_low_confidence(0.07)

benign(0.085)

TCGA-CI-6624-01

Colorectum

rectum 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

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