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:0048732	Colorectum	AD	gland development	149/3918	436/18723	6.07e-11	6.33e-09	149
GO:0022612	Colorectum	AD	gland morphogenesis	42/3918	118/18723	1.62e-04	2.23e-03	42
GO:0043123	Colorectum	AD	positive regulation of I-kappaB kinase/NF-kappaB signaling	60/3918	186/18723	1.91e-04	2.56e-03	60
GO:0043122	Colorectum	AD	regulation of I-kappaB kinase/NF-kappaB signaling	76/3918	249/18723	2.17e-04	2.85e-03	76
GO:0051403	Colorectum	AD	stress-activated MAPK cascade	72/3918	239/18723	4.77e-04	5.25e-03	72
GO:0031098	Colorectum	AD	stress-activated protein kinase signaling cascade	74/3918	247/18723	4.80e-04	5.27e-03	74
GO:0007249	Colorectum	AD	I-kappaB kinase/NF-kappaB signaling	82/3918	281/18723	6.09e-04	6.40e-03	82
GO:0070302	Colorectum	AD	regulation of stress-activated protein kinase signaling cascade	58/3918	195/18723	2.21e-03	1.74e-02	58
GO:0032872	Colorectum	AD	regulation of stress-activated MAPK cascade	57/3918	192/18723	2.51e-03	1.92e-02	57
GO:0035148	Colorectum	AD	tube formation	45/3918	148/18723	4.13e-03	2.87e-02	45
GO:0008544	Colorectum	AD	epidermis development	87/3918	324/18723	5.99e-03	3.76e-02	87
GO:00487322	Colorectum	MSS	gland development	143/3467	436/18723	3.85e-13	8.01e-11	143
GO:00226122	Colorectum	MSS	gland morphogenesis	41/3467	118/18723	2.02e-05	4.30e-04	41
GO:00431221	Colorectum	MSS	regulation of I-kappaB kinase/NF-kappaB signaling	71/3467	249/18723	7.12e-05	1.21e-03	71
GO:00072491	Colorectum	MSS	I-kappaB kinase/NF-kappaB signaling	77/3467	281/18723	1.51e-04	2.19e-03	77
GO:00431231	Colorectum	MSS	positive regulation of I-kappaB kinase/NF-kappaB signaling	55/3467	186/18723	1.60e-04	2.29e-03	55
GO:00310982	Colorectum	MSS	stress-activated protein kinase signaling cascade	67/3467	247/18723	5.28e-04	5.99e-03	67
GO:00514032	Colorectum	MSS	stress-activated MAPK cascade	65/3467	239/18723	5.87e-04	6.49e-03	65
GO:00351481	Colorectum	MSS	tube formation	44/3467	148/18723	6.06e-04	6.68e-03	44
GO:00703021	Colorectum	MSS	regulation of stress-activated protein kinase signaling cascade	52/3467	195/18723	3.07e-03	2.34e-02	52

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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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