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: MMP2

Gene summary for MMP2

Gene summary.

Gene information	Species	Human
	Gene symbol	MMP2
	Gene ID	4313
	Gene name	matrix metallopeptidase 2
	Gene Alias	CLG4
	Cytomap	16q12.2
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	P08253

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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
4313	MMP2	AEH-subject1	Human	Endometrium	AEH	5.07e-19	-6.37e-01	-0.3059
4313	MMP2	AEH-subject2	Human	Endometrium	AEH	1.85e-24	-7.09e-01	-0.2525
4313	MMP2	AEH-subject3	Human	Endometrium	AEH	9.84e-33	-7.89e-01	-0.2576
4313	MMP2	AEH-subject4	Human	Endometrium	AEH	2.50e-13	-6.27e-01	-0.2657
4313	MMP2	AEH-subject5	Human	Endometrium	AEH	2.36e-40	-8.18e-01	-0.2953
4313	MMP2	EEC-subject1	Human	Endometrium	EEC	1.99e-26	-7.44e-01	-0.2682
4313	MMP2	EEC-subject2	Human	Endometrium	EEC	1.20e-41	-8.14e-01	-0.2607
4313	MMP2	EEC-subject3	Human	Endometrium	EEC	3.14e-31	-6.47e-01	-0.2525
4313	MMP2	EEC-subject4	Human	Endometrium	EEC	7.49e-29	-7.61e-01	-0.2571
4313	MMP2	EEC-subject5	Human	Endometrium	EEC	6.74e-33	-7.70e-01	-0.249
4313	MMP2	GSM5276935	Human	Endometrium	EEC	3.89e-30	-7.50e-01	-0.123
4313	MMP2	GSM6177620_NYU_UCEC1_lib1_lib1	Human	Endometrium	EEC	1.79e-24	-7.22e-01	-0.1869
4313	MMP2	GSM6177620_NYU_UCEC1_lib2_lib2	Human	Endometrium	EEC	1.49e-24	-6.90e-01	-0.1875
4313	MMP2	GSM6177620_NYU_UCEC1_lib3_lib3	Human	Endometrium	EEC	1.99e-28	-6.57e-01	-0.1883
4313	MMP2	GSM6177621_NYU_UCEC2_lib1_lib1	Human	Endometrium	EEC	1.71e-39	-7.78e-01	-0.1934
4313	MMP2	GSM6177622_NYU_UCEC3_lib1_lib1	Human	Endometrium	EEC	1.19e-42	-8.16e-01	-0.1917
4313	MMP2	GSM6177622_NYU_UCEC3_lib2_lib2	Human	Endometrium	EEC	6.57e-48	-8.29e-01	-0.1916
4313	MMP2	P2T-E	Human	Esophagus	ESCC	1.02e-09	3.20e-01	0.1177
4313	MMP2	P4T-E	Human	Esophagus	ESCC	1.56e-04	1.39e+00	0.1323
4313	MMP2	P9T-E	Human	Esophagus	ESCC	1.22e-07	1.70e+00	0.1131

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
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
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:0104004110	Skin	SCCIS	cellular response to environmental stimulus	36/919	331/18723	6.89e-06	2.67e-04	36
GO:000736914	Skin	SCCIS	gastrulation	24/919	185/18723	1.33e-05	4.40e-04	24
GO:00301985	Skin	SCCIS	extracellular matrix organization	32/919	301/18723	3.46e-05	9.17e-04	32
GO:00430625	Skin	SCCIS	extracellular structure organization	32/919	302/18723	3.69e-05	9.65e-04	32
GO:00452295	Skin	SCCIS	external encapsulating structure organization	32/919	304/18723	4.20e-05	1.06e-03	32
GO:007147817	Skin	SCCIS	cellular response to radiation	23/919	186/18723	4.31e-05	1.08e-03	23
GO:007122913	Skin	SCCIS	cellular response to acid chemical	12/919	80/18723	5.04e-04	7.91e-03	12
GO:000756516	Skin	SCCIS	female pregnancy	21/919	193/18723	5.39e-04	8.30e-03	21
GO:0062197112	Skin	SCCIS	cellular response to chemical stress	31/919	337/18723	6.10e-04	9.06e-03	31
GO:007123013	Skin	SCCIS	cellular response to amino acid stimulus	11/919	71/18723	6.45e-04	9.46e-03	11
GO:004801311	Skin	SCCIS	ephrin receptor signaling pathway	9/919	51/18723	7.53e-04	1.03e-02	9
GO:000170413	Skin	SCCIS	formation of primary germ layer	15/919	121/18723	8.61e-04	1.14e-02	15
GO:004877111	Skin	SCCIS	tissue remodeling	19/919	175/18723	9.98e-04	1.25e-02	19
GO:000756616	Skin	SCCIS	embryo implantation	9/919	53/18723	1.01e-03	1.25e-02	9
GO:0001666112	Skin	SCCIS	response to hypoxia	28/919	307/18723	1.25e-03	1.46e-02	28
GO:0006839111	Skin	SCCIS	mitochondrial transport	24/919	254/18723	1.68e-03	1.84e-02	24
GO:00329632	Skin	SCCIS	collagen metabolic process	13/919	104/18723	1.72e-03	1.87e-02	13
GO:0072594111	Skin	SCCIS	establishment of protein localization to organelle	35/919	422/18723	1.77e-03	1.90e-02	35
GO:000941612	Skin	SCCIS	response to light stimulus	28/919	320/18723	2.29e-03	2.30e-02	28
GO:0036293112	Skin	SCCIS	response to decreased oxygen levels	28/919	322/18723	2.51e-03	2.43e-02	28

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0541525	Endometrium	AEH	Diabetic cardiomyopathy	86/1197	203/8465	2.62e-23	1.22e-21	8.90e-22	86
hsa0541826	Endometrium	AEH	Fluid shear stress and atherosclerosis	43/1197	139/8465	2.47e-07	3.49e-06	2.55e-06	43
hsa0467026	Endometrium	AEH	Leukocyte transendothelial migration	37/1197	114/8465	4.51e-07	6.11e-06	4.47e-06	37
hsa0520518	Endometrium	AEH	Proteoglycans in cancer	53/1197	205/8465	5.43e-06	6.53e-05	4.78e-05	53
hsa049337	Endometrium	AEH	AGE-RAGE signaling pathway in diabetic complications	28/1197	100/8465	2.11e-04	1.80e-03	1.32e-03	28
hsa0491525	Endometrium	AEH	Estrogen signaling pathway	35/1197	138/8465	3.10e-04	2.40e-03	1.75e-03	35
hsa05415111	Endometrium	AEH	Diabetic cardiomyopathy	86/1197	203/8465	2.62e-23	1.22e-21	8.90e-22	86
hsa05418112	Endometrium	AEH	Fluid shear stress and atherosclerosis	43/1197	139/8465	2.47e-07	3.49e-06	2.55e-06	43
hsa04670111	Endometrium	AEH	Leukocyte transendothelial migration	37/1197	114/8465	4.51e-07	6.11e-06	4.47e-06	37
hsa0520519	Endometrium	AEH	Proteoglycans in cancer	53/1197	205/8465	5.43e-06	6.53e-05	4.78e-05	53
hsa0493314	Endometrium	AEH	AGE-RAGE signaling pathway in diabetic complications	28/1197	100/8465	2.11e-04	1.80e-03	1.32e-03	28
hsa04915111	Endometrium	AEH	Estrogen signaling pathway	35/1197	138/8465	3.10e-04	2.40e-03	1.75e-03	35
hsa0541526	Endometrium	EEC	Diabetic cardiomyopathy	86/1237	203/8465	2.59e-22	9.46e-21	7.05e-21	86
hsa0541827	Endometrium	EEC	Fluid shear stress and atherosclerosis	45/1237	139/8465	7.76e-08	1.22e-06	9.07e-07	45
hsa0467027	Endometrium	EEC	Leukocyte transendothelial migration	36/1237	114/8465	2.97e-06	3.91e-05	2.91e-05	36
hsa0520524	Endometrium	EEC	Proteoglycans in cancer	52/1237	205/8465	3.01e-05	3.19e-04	2.38e-04	52
hsa0493321	Endometrium	EEC	AGE-RAGE signaling pathway in diabetic complications	28/1237	100/8465	3.68e-04	3.03e-03	2.26e-03	28
hsa0491526	Endometrium	EEC	Estrogen signaling pathway	34/1237	138/8465	1.19e-03	8.02e-03	5.98e-03	34
hsa0541535	Endometrium	EEC	Diabetic cardiomyopathy	86/1237	203/8465	2.59e-22	9.46e-21	7.05e-21	86
hsa0541836	Endometrium	EEC	Fluid shear stress and atherosclerosis	45/1237	139/8465	7.76e-08	1.22e-06	9.07e-07	45

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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

MMP2

SNV

Missense_Mutation

c.1116N>C

p.Lys372Asn

p.K372N

P08253

protein_coding

deleterious(0.02)

probably_damaging(0.994)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MMP2

SNV

Missense_Mutation

rs759302357

c.682G>A

p.Ala228Thr

p.A228T

P08253

protein_coding

deleterious(0)

probably_damaging(0.935)

TCGA-AR-A0U2-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

tamoxiphen

MMP2

SNV

Missense_Mutation

novel

c.1512N>T

p.Met504Ile

p.M504I

P08253

protein_coding

tolerated(0.2)

benign(0)

TCGA-EW-A6S9-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

MMP2

SNV

Missense_Mutation

c.970G>A

p.Asp324Asn

p.D324N

P08253

protein_coding

deleterious(0.01)

benign(0.074)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MMP2

SNV

Missense_Mutation

rs772094112

c.275N>G

p.Asn92Ser

p.N92S

P08253

protein_coding

tolerated(0.73)

benign(0)

TCGA-C5-A3HL-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

MMP2

SNV

Missense_Mutation

c.1295G>C

p.Arg432Pro

p.R432P

P08253

protein_coding

tolerated(0.35)

probably_damaging(0.999)

TCGA-EK-A2PI-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

MMP2

SNV

Missense_Mutation

c.1116N>C

p.Lys372Asn

p.K372N

P08253

protein_coding

deleterious(0.02)

probably_damaging(0.994)

TCGA-IR-A3LA-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MMP2

SNV

Missense_Mutation

c.1345C>G

p.Pro449Ala

p.P449A

P08253

protein_coding

deleterious(0.01)

benign(0.001)

TCGA-IR-A3LH-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MMP2

SNV

Missense_Mutation

c.1818C>G

p.Ile606Met

p.I606M

P08253

protein_coding

tolerated(0.14)

probably_damaging(0.999)

TCGA-Q1-A73O-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MMP2

SNV

Missense_Mutation

c.1896C>G

p.Phe632Leu

p.F632L

P08253

protein_coding

tolerated(0.24)

probably_damaging(0.966)

TCGA-Q1-A73O-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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
4313	MMP2	NEUTRAL ZINC METALLOPEPTIDASE, ENZYME, DRUGGABLE GENOME, PROTEASE	inhibitor	178101832
4313	MMP2	NEUTRAL ZINC METALLOPEPTIDASE, ENZYME, DRUGGABLE GENOME, PROTEASE		SERMS		15576828
4313	MMP2	NEUTRAL ZINC METALLOPEPTIDASE, ENZYME, DRUGGABLE GENOME, PROTEASE		MARIMASTAT	MARIMASTAT
4313	MMP2	NEUTRAL ZINC METALLOPEPTIDASE, ENZYME, DRUGGABLE GENOME, PROTEASE		PMID29130358-Compound-SB-3CT
4313	MMP2	NEUTRAL ZINC METALLOPEPTIDASE, ENZYME, DRUGGABLE GENOME, PROTEASE		BMS-275291	REBIMASTAT	15041713
4313	MMP2	NEUTRAL ZINC METALLOPEPTIDASE, ENZYME, DRUGGABLE GENOME, PROTEASE		SIMVASTATIN	SIMVASTATIN	16436088
4313	MMP2	NEUTRAL ZINC METALLOPEPTIDASE, ENZYME, DRUGGABLE GENOME, PROTEASE		POLYPHENOL		15324350
4313	MMP2	NEUTRAL ZINC METALLOPEPTIDASE, ENZYME, DRUGGABLE GENOME, PROTEASE		HEPARAN SULFATE		12972284
4313	MMP2	NEUTRAL ZINC METALLOPEPTIDASE, ENZYME, DRUGGABLE GENOME, PROTEASE		PRAVASTATIN	PRAVASTATIN	15842807
4313	MMP2	NEUTRAL ZINC METALLOPEPTIDASE, ENZYME, DRUGGABLE GENOME, PROTEASE		RO-26-2853

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