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:001605513	Endometrium	EEC	Wnt signaling pathway	90/2168	444/18723	6.65e-08	3.50e-06	90
GO:019873813	Endometrium	EEC	cell-cell signaling by wnt	90/2168	446/18723	8.25e-08	4.23e-06	90
GO:000716014	Endometrium	EEC	cell-matrix adhesion	54/2168	233/18723	3.98e-07	1.56e-05	54
GO:006082813	Endometrium	EEC	regulation of canonical Wnt signaling pathway	56/2168	253/18723	1.18e-06	3.90e-05	56
GO:004873217	Endometrium	EEC	gland development	83/2168	436/18723	3.08e-06	8.48e-05	83
GO:004312216	Endometrium	EEC	regulation of I-kappaB kinase/NF-kappaB signaling	53/2168	249/18723	7.59e-06	1.73e-04	53
GO:006007013	Endometrium	EEC	canonical Wnt signaling pathway	61/2168	303/18723	1.05e-05	2.25e-04	61
GO:004312314	Endometrium	EEC	positive regulation of I-kappaB kinase/NF-kappaB signaling	42/2168	186/18723	1.47e-05	2.87e-04	42
GO:000724915	Endometrium	EEC	I-kappaB kinase/NF-kappaB signaling	57/2168	281/18723	1.60e-05	3.12e-04	57
GO:003017713	Endometrium	EEC	positive regulation of Wnt signaling pathway	34/2168	140/18723	1.89e-05	3.50e-04	34
GO:002261212	Endometrium	EEC	gland morphogenesis	30/2168	118/18723	2.25e-05	4.02e-04	30
GO:009026313	Endometrium	EEC	positive regulation of canonical Wnt signaling pathway	26/2168	106/18723	1.46e-04	1.87e-03	26
GO:190122411	Endometrium	EEC	positive regulation of NIK/NF-kappaB signaling	19/2168	69/18723	2.27e-04	2.70e-03	19
GO:005109013	Endometrium	EEC	regulation of DNA-binding transcription factor activity	75/2168	440/18723	3.71e-04	3.97e-03	75
GO:19012222	Endometrium	EEC	regulation of NIK/NF-kappaB signaling	24/2168	112/18723	2.00e-03	1.51e-02	24
GO:003514813	Endometrium	EEC	tube formation	29/2168	148/18723	3.07e-03	2.13e-02	29
GO:004358814	Endometrium	EEC	skin development	45/2168	263/18723	4.69e-03	2.99e-02	45
GO:000854414	Endometrium	EEC	epidermis development	53/2168	324/18723	5.92e-03	3.54e-02	53
GO:006054112	Endometrium	EEC	respiratory system development	36/2168	203/18723	6.02e-03	3.57e-02	36
GO:00380612	Endometrium	EEC	NIK/NF-kappaB signaling	27/2168	143/18723	6.99e-03	4.01e-02	27

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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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