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: ECM1

Gene summary for ECM1

Gene summary.

Gene information	Species	Human
	Gene symbol	ECM1
	Gene ID	1893
	Gene name	extracellular matrix protein 1
	Gene Alias	URBWD
	Cytomap	1q21.2
	Gene Type	protein-coding
	GO ID	GO:0001501
	UniProtAcc	Q16610

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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
1893	ECM1	GSM4909297	Human	Breast	IDC	1.05e-07	3.41e-01	0.1517
1893	ECM1	GSM4909306	Human	Breast	IDC	9.39e-24	5.28e-01	0.1564
1893	ECM1	GSM4909307	Human	Breast	IDC	1.96e-23	4.90e-01	0.1569
1893	ECM1	GSM4909308	Human	Breast	IDC	6.91e-59	8.54e-01	0.158
1893	ECM1	GSM4909317	Human	Breast	IDC	1.63e-02	1.04e-01	0.1355
1893	ECM1	P3	Human	Breast	IDC	2.07e-06	4.27e-01	0.1542
1893	ECM1	CA_HPV_2	Human	Cervix	CC	1.41e-02	2.25e-01	0.0391
1893	ECM1	CCI_1	Human	Cervix	CC	3.36e-06	7.23e-01	0.528
1893	ECM1	Tumor	Human	Cervix	CC	2.70e-31	6.47e-01	0.1241
1893	ECM1	sample3	Human	Cervix	CC	3.65e-58	9.28e-01	0.1387
1893	ECM1	H2	Human	Cervix	HSIL_HPV	6.10e-27	8.87e-01	0.0632
1893	ECM1	T3	Human	Cervix	CC	5.90e-60	9.62e-01	0.1389
1893	ECM1	AEH-subject1	Human	Endometrium	AEH	9.85e-49	-8.81e-01	-0.3059
1893	ECM1	AEH-subject2	Human	Endometrium	AEH	1.65e-35	-8.48e-01	-0.2525
1893	ECM1	AEH-subject3	Human	Endometrium	AEH	1.03e-23	-7.16e-01	-0.2576
1893	ECM1	AEH-subject4	Human	Endometrium	AEH	7.01e-18	-7.08e-01	-0.2657
1893	ECM1	AEH-subject5	Human	Endometrium	AEH	1.24e-45	-9.21e-01	-0.2953
1893	ECM1	EEC-subject1	Human	Endometrium	EEC	1.74e-40	-8.75e-01	-0.2682
1893	ECM1	EEC-subject2	Human	Endometrium	EEC	4.60e-46	-9.09e-01	-0.2607
1893	ECM1	EEC-subject3	Human	Endometrium	EEC	1.07e-33	-7.81e-01	-0.2525

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
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
Thyroid		ATC: Anaplastic thyroid cancer
		HT: Hashimoto's thyroiditis
		PTC: Papillary thyroid 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:005254714	Breast	IDC	regulation of peptidase activity	96/1434	461/18723	7.58e-20	6.15e-17	96
GO:004586114	Breast	IDC	negative regulation of proteolysis	70/1434	351/18723	8.21e-14	2.22e-11	70
GO:005134613	Breast	IDC	negative regulation of hydrolase activity	71/1434	379/18723	1.33e-12	2.90e-10	71
GO:001046613	Breast	IDC	negative regulation of peptidase activity	56/1434	262/18723	1.39e-12	2.92e-10	56
GO:005090011	Breast	IDC	leukocyte migration	54/1434	369/18723	3.10e-06	1.15e-04	54
GO:005067313	Breast	IDC	epithelial cell proliferation	60/1434	437/18723	7.13e-06	2.15e-04	60
GO:005067812	Breast	IDC	regulation of epithelial cell proliferation	54/1434	381/18723	8.07e-06	2.39e-04	54
GO:000268511	Breast	IDC	regulation of leukocyte migration	33/1434	210/18723	6.10e-05	1.27e-03	33
GO:00457651	Breast	IDC	regulation of angiogenesis	45/1434	342/18723	2.57e-04	3.98e-03	45
GO:19013421	Breast	IDC	regulation of vasculature development	45/1434	348/18723	3.78e-04	5.38e-03	45
GO:007167511	Breast	IDC	regulation of mononuclear cell migration	20/1434	115/18723	4.35e-04	5.90e-03	20
GO:007167411	Breast	IDC	mononuclear cell migration	29/1434	196/18723	4.68e-04	6.26e-03	29
GO:000150311	Breast	IDC	ossification	50/1434	408/18723	6.51e-04	8.04e-03	50
GO:00431227	Breast	IDC	regulation of I-kappaB kinase/NF-kappaB signaling	34/1434	249/18723	7.18e-04	8.77e-03	34
GO:000724914	Breast	IDC	I-kappaB kinase/NF-kappaB signaling	37/1434	281/18723	8.58e-04	9.98e-03	37
GO:005067911	Breast	IDC	positive regulation of epithelial cell proliferation	29/1434	207/18723	1.14e-03	1.24e-02	29
GO:00457661	Breast	IDC	positive regulation of angiogenesis	26/1434	181/18723	1.39e-03	1.43e-02	26
GO:19040181	Breast	IDC	positive regulation of vasculature development	26/1434	181/18723	1.39e-03	1.43e-02	26
GO:00431236	Breast	IDC	positive regulation of I-kappaB kinase/NF-kappaB signaling	26/1434	186/18723	2.06e-03	1.95e-02	26
GO:2000404	Breast	IDC	regulation of T cell migration	9/1434	42/18723	3.91e-03	3.20e-02	9

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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

ECM1

SNV

Missense_Mutation

c.1087C>A

p.Leu363Met

p.L363M

Q16610

protein_coding

deleterious(0.01)

benign(0.346)

TCGA-A2-A04R-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxol

ECM1

SNV

Missense_Mutation

c.1456N>C

p.Cys486Arg

p.C486R

Q16610

protein_coding

deleterious(0.01)

probably_damaging(0.932)

TCGA-BH-A0B9-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

ECM1

SNV

Missense_Mutation

c.817N>A

p.Glu273Lys

p.E273K

Q16610

protein_coding

tolerated(0.08)

probably_damaging(0.984)

TCGA-BH-A18P-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ECM1

SNV

Missense_Mutation

c.439N>G

p.Leu147Val

p.L147V

Q16610

protein_coding

tolerated(0.25)

benign(0.364)

TCGA-EW-A1J5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

ECM1

SNV

Missense_Mutation

novel

c.212G>A

p.Gly71Glu

p.G71E

Q16610

protein_coding

tolerated_low_confidence(0.34)

benign(0.074)

TCGA-PE-A5DE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

ECM1

insertion

Frame_Shift_Ins

novel

c.1534_1535insCTTTCACACCAACA

p.Leu512ProfsTer10

p.L512Pfs*10

Q16610

protein_coding

TCGA-A2-A0CM-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

ECM1

SNV

Missense_Mutation

rs587674518

c.703G>A

p.Glu235Lys

p.E235K

Q16610

protein_coding

tolerated(0.08)

possibly_damaging(0.597)

TCGA-JW-AAVH-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

ECM1

SNV

Missense_Mutation

c.616N>G

p.Gln206Glu

p.Q206E

Q16610

protein_coding

deleterious(0.02)

probably_damaging(0.978)

TCGA-MY-A5BE-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

ECM1

SNV

Missense_Mutation

c.376N>A

p.Glu126Lys

p.E126K

Q16610

protein_coding

tolerated(0.19)

benign(0.007)

TCGA-Q1-A5R2-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ECM1

SNV

Missense_Mutation

novel

c.1103N>C

p.Leu368Pro

p.L368P

Q16610

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-5M-AAT6-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

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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