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: MMP1

Gene summary for MMP1

Gene summary.

Gene information	Species	Human
	Gene symbol	MMP1
	Gene ID	4312
	Gene name	matrix metallopeptidase 1
	Gene Alias	CLG
	Cytomap	11q22.2
	Gene Type	protein-coding
	GO ID	GO:0006508
	UniProtAcc	B4DN15

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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
4312	MMP1	ctrl6	Human	Breast	Precancer	3.19e-30	7.01e-01	-0.0061
4312	MMP1	CA_HPV_2	Human	Cervix	CC	3.06e-02	1.83e-01	0.0391
4312	MMP1	Tumor	Human	Cervix	CC	1.17e-41	1.06e+00	0.1241
4312	MMP1	sample3	Human	Cervix	CC	1.45e-62	1.25e+00	0.1387
4312	MMP1	T3	Human	Cervix	CC	7.82e-54	1.22e+00	0.1389
4312	MMP1	P11T-E	Human	Esophagus	ESCC	2.60e-08	4.44e+00	0.1426
4312	MMP1	P12T-E	Human	Esophagus	ESCC	3.04e-04	-2.64e-01	0.1122
4312	MMP1	P16T-E	Human	Esophagus	ESCC	1.31e-02	-2.70e-01	0.1153
4312	MMP1	P21T-E	Human	Esophagus	ESCC	2.14e-19	2.39e+00	0.1617
4312	MMP1	P28T-E	Human	Esophagus	ESCC	3.14e-02	-2.55e-01	0.1149
4312	MMP1	P37T-E	Human	Esophagus	ESCC	4.32e-16	2.23e+00	0.1371
4312	MMP1	P39T-E	Human	Esophagus	ESCC	8.84e-05	-2.75e-01	0.0894
4312	MMP1	P65T-E	Human	Esophagus	ESCC	2.37e-03	9.18e-01	0.0978
4312	MMP1	P74T-E	Human	Esophagus	ESCC	1.49e-03	6.38e-01	0.1479
4312	MMP1	P75T-E	Human	Esophagus	ESCC	1.04e-03	2.38e+00	0.1125
4312	MMP1	P89T-E	Human	Esophagus	ESCC	6.99e-06	2.77e+00	0.1752
4312	MMP1	P91T-E	Human	Esophagus	ESCC	1.54e-03	2.87e+00	0.1828
4312	MMP1	P107T-E	Human	Esophagus	ESCC	6.54e-07	1.07e+00	0.171
4312	MMP1	P126T-E	Human	Esophagus	ESCC	1.55e-06	2.16e+00	0.1125
4312	MMP1	P127T-E	Human	Esophagus	ESCC	9.39e-03	-1.25e-01	0.0826

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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
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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:00432549	Breast	Precancer	regulation of protein-containing complex assembly	50/1080	428/18723	1.63e-06	5.97e-05	50
GO:00313349	Breast	Precancer	positive regulation of protein-containing complex assembly	33/1080	237/18723	2.39e-06	8.21e-05	33
GO:00093148	Breast	Precancer	response to radiation	47/1080	456/18723	8.39e-05	1.62e-03	47
GO:00712147	Breast	Precancer	cellular response to abiotic stimulus	37/1080	331/18723	9.12e-05	1.73e-03	37
GO:01040047	Breast	Precancer	cellular response to environmental stimulus	37/1080	331/18723	9.12e-05	1.73e-03	37
GO:00714785	Breast	Precancer	cellular response to radiation	24/1080	186/18723	1.83e-04	2.96e-03	24
GO:00224119	Breast	Precancer	cellular component disassembly	44/1080	443/18723	3.17e-04	4.51e-03	44
GO:0070141	Breast	Precancer	response to UV-A	4/1080	14/18723	6.92e-03	4.67e-02	4
GO:004325410	Cervix	CC	regulation of protein-containing complex assembly	96/2311	428/18723	2.91e-09	3.05e-07	96
GO:003133410	Cervix	CC	positive regulation of protein-containing complex assembly	55/2311	237/18723	2.25e-06	6.73e-05	55
GO:00712148	Cervix	CC	cellular response to abiotic stimulus	69/2311	331/18723	7.36e-06	1.73e-04	69
GO:01040048	Cervix	CC	cellular response to environmental stimulus	69/2311	331/18723	7.36e-06	1.73e-04	69
GO:00093149	Cervix	CC	response to radiation	86/2311	456/18723	3.50e-05	5.63e-04	86
GO:002241110	Cervix	CC	cellular component disassembly	83/2311	443/18723	6.04e-05	8.68e-04	83
GO:00714786	Cervix	CC	cellular response to radiation	41/2311	186/18723	1.41e-04	1.71e-03	41
GO:00094112	Cervix	CC	response to UV	33/2311	149/18723	5.51e-04	5.29e-03	33
GO:00015037	Cervix	CC	ossification	71/2311	408/18723	1.67e-03	1.28e-02	71
GO:00346442	Cervix	CC	cellular response to UV	20/2311	90/18723	6.05e-03	3.44e-02	20
GO:0030198	Cervix	CC	extracellular matrix organization	52/2311	301/18723	7.43e-03	3.98e-02	52
GO:0043062	Cervix	CC	extracellular structure organization	52/2311	302/18723	7.92e-03	4.17e-02	52

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0517118	Breast	Precancer	Coronavirus disease - COVID-19	81/684	232/8465	3.74e-32	2.36e-30	1.81e-30	81
hsa0541718	Breast	Precancer	Lipid and atherosclerosis	37/684	215/8465	7.64e-06	9.29e-05	7.12e-05	37
hsa0465716	Breast	Precancer	IL-17 signaling pathway	20/684	94/8465	4.74e-05	4.54e-04	3.48e-04	20
hsa0532312	Breast	Precancer	Rheumatoid arthritis	19/684	93/8465	1.30e-04	1.14e-03	8.73e-04	19
hsa052196	Breast	Precancer	Bladder cancer	9/684	41/8465	4.65e-03	2.72e-02	2.08e-02	9
hsa0517119	Breast	Precancer	Coronavirus disease - COVID-19	81/684	232/8465	3.74e-32	2.36e-30	1.81e-30	81
hsa0541719	Breast	Precancer	Lipid and atherosclerosis	37/684	215/8465	7.64e-06	9.29e-05	7.12e-05	37
hsa0465717	Breast	Precancer	IL-17 signaling pathway	20/684	94/8465	4.74e-05	4.54e-04	3.48e-04	20
hsa0532313	Breast	Precancer	Rheumatoid arthritis	19/684	93/8465	1.30e-04	1.14e-03	8.73e-04	19
hsa0521913	Breast	Precancer	Bladder cancer	9/684	41/8465	4.65e-03	2.72e-02	2.08e-02	9
hsa0517120	Cervix	CC	Coronavirus disease - COVID-19	111/1267	232/8465	1.82e-33	5.90e-31	3.49e-31	111
hsa0541720	Cervix	CC	Lipid and atherosclerosis	65/1267	215/8465	6.47e-09	1.10e-07	6.52e-08	65
hsa0465718	Cervix	CC	IL-17 signaling pathway	31/1267	94/8465	8.71e-06	7.43e-05	4.39e-05	31
hsa052197	Cervix	CC	Bladder cancer	16/1267	41/8465	1.45e-04	9.05e-04	5.35e-04	16
hsa0532314	Cervix	CC	Rheumatoid arthritis	27/1267	93/8465	3.64e-04	1.82e-03	1.07e-03	27
hsa049265	Cervix	CC	Relaxin signaling pathway	30/1267	129/8465	7.92e-03	2.56e-02	1.51e-02	30
hsa05171110	Cervix	CC	Coronavirus disease - COVID-19	111/1267	232/8465	1.82e-33	5.90e-31	3.49e-31	111
hsa05417110	Cervix	CC	Lipid and atherosclerosis	65/1267	215/8465	6.47e-09	1.10e-07	6.52e-08	65
hsa0465719	Cervix	CC	IL-17 signaling pathway	31/1267	94/8465	8.71e-06	7.43e-05	4.39e-05	31
hsa0521914	Cervix	CC	Bladder cancer	16/1267	41/8465	1.45e-04	9.05e-04	5.35e-04	16

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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

MMP1

SNV

Missense_Mutation

novel

c.593N>T

p.Asp198Val

p.D198V

P03956

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-A7-A56D-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

MMP1

SNV

Missense_Mutation

novel

c.139G>T

p.Asp47Tyr

p.D47Y

P03956

protein_coding

deleterious(0.03)

benign(0.183)

TCGA-A8-A06Q-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

MMP1

insertion

Frame_Shift_Ins

novel

c.1264_1265insAACACCTTCT

p.Ile422LysfsTer9

p.I422Kfs*9

P03956

protein_coding

TCGA-AR-A0TU-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Doxorubicin

MMP1

insertion

Nonsense_Mutation

novel

c.319_320insATTTATCAGTTTTGTAAATAAGAAAAATATTAAATATTAGG

p.Pro107HisfsTer6

p.P107Hfs*6

P03956

protein_coding

TCGA-BH-A0B8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

MMP1

SNV

Missense_Mutation

c.403N>C

p.Glu135Gln

p.E135Q

P03956

protein_coding

tolerated(0.25)

benign(0.034)

TCGA-DG-A2KM-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MMP1

SNV

Missense_Mutation

rs754506439

c.1021N>T

p.Arg341Trp

p.R341W

P03956

protein_coding

deleterious(0.01)

probably_damaging(0.989)

TCGA-DS-A7WH-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MMP1

SNV

Missense_Mutation

novel

c.385N>A

p.Asp129Asn

p.D129N

P03956

protein_coding

tolerated(0.05)

benign(0.152)

TCGA-IR-A3LH-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MMP1

SNV

Missense_Mutation

c.533N>C

p.Gly178Ala

p.G178A

P03956

protein_coding

deleterious(0.03)

benign(0.162)

TCGA-IR-A3LK-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

MMP1

SNV

Missense_Mutation

novel

c.484N>C

p.Ser162Pro

p.S162P

P03956

protein_coding

deleterious(0)

probably_damaging(0.988)

TCGA-A6-2675-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

MMP1

SNV

Missense_Mutation

c.1078N>C

p.Tyr360His

p.Y360H

P03956

protein_coding

deleterious(0.02)

probably_damaging(0.983)

TCGA-AA-3672-01

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
4312	MMP1	DRUGGABLE GENOME, PROTEASE, ENZYME		PMID29130358-Compound-Figure18(14a)
4312	MMP1	DRUGGABLE GENOME, PROTEASE, ENZYME		RIBAVIRIN	RIBAVIRIN	16699498
4312	MMP1	DRUGGABLE GENOME, PROTEASE, ENZYME	inhibitor	252827503	CGS-27023A
4312	MMP1	DRUGGABLE GENOME, PROTEASE, ENZYME	inhibitor	CHEMBL2364574	DOXYCYCLINE CALCIUM
4312	MMP1	DRUGGABLE GENOME, PROTEASE, ENZYME		IMMUNOSUPPRESSIVE		16914544
4312	MMP1	DRUGGABLE GENOME, PROTEASE, ENZYME		LAMIVUDINE	LAMIVUDINE	15309715
4312	MMP1	DRUGGABLE GENOME, PROTEASE, ENZYME		TYROSINE KINASE INHIBITOR		15324351
4312	MMP1	DRUGGABLE GENOME, PROTEASE, ENZYME		PMID29130358-Compound-Figure10(2a)
4312	MMP1	DRUGGABLE GENOME, PROTEASE, ENZYME	inhibitor	178103080	CIPEMASTAT
4312	MMP1	DRUGGABLE GENOME, PROTEASE, ENZYME		Marimastat	MARIMASTAT

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