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: MFAP2

Gene summary for MFAP2

Gene summary.

Gene information	Species	Human
	Gene symbol	MFAP2
	Gene ID	4237
	Gene name	microfibril associated protein 2
	Gene Alias	MAGP
	Cytomap	1p36.13
	Gene Type	protein-coding
	GO ID	GO:0001654
	UniProtAcc	P55001

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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
4237	MFAP2	GSM4909281	Human	Breast	IDC	4.81e-39	6.09e-01	0.21
4237	MFAP2	GSM4909282	Human	Breast	IDC	1.75e-06	2.20e-01	-0.0288
4237	MFAP2	GSM4909285	Human	Breast	IDC	1.17e-04	1.43e-01	0.21
4237	MFAP2	GSM4909286	Human	Breast	IDC	5.01e-05	1.55e-01	0.1081
4237	MFAP2	GSM4909287	Human	Breast	IDC	7.68e-15	3.91e-01	0.2057
4237	MFAP2	GSM4909293	Human	Breast	IDC	4.78e-02	1.30e-01	0.1581
4237	MFAP2	GSM4909295	Human	Breast	IDC	9.82e-16	5.37e-01	0.0898
4237	MFAP2	LZE4T	Human	Esophagus	ESCC	1.07e-21	8.21e-01	0.0811
4237	MFAP2	LZE5T	Human	Esophagus	ESCC	1.23e-06	5.76e-01	0.0514
4237	MFAP2	LZE7T	Human	Esophagus	ESCC	3.72e-10	7.65e-01	0.0667
4237	MFAP2	LZE8T	Human	Esophagus	ESCC	2.46e-12	4.53e-01	0.067
4237	MFAP2	LZE20T	Human	Esophagus	ESCC	6.47e-08	3.52e-01	0.0662
4237	MFAP2	LZE22T	Human	Esophagus	ESCC	8.43e-11	1.68e+00	0.068
4237	MFAP2	LZE24T	Human	Esophagus	ESCC	4.55e-42	1.31e+00	0.0596
4237	MFAP2	LZE21T	Human	Esophagus	ESCC	2.16e-05	5.00e-01	0.0655
4237	MFAP2	LZE6T	Human	Esophagus	ESCC	1.13e-10	4.95e-01	0.0845
4237	MFAP2	P1T-E	Human	Esophagus	ESCC	1.21e-10	9.35e-01	0.0875
4237	MFAP2	P2T-E	Human	Esophagus	ESCC	2.49e-91	1.86e+00	0.1177
4237	MFAP2	P4T-E	Human	Esophagus	ESCC	2.05e-80	1.88e+00	0.1323
4237	MFAP2	P5T-E	Human	Esophagus	ESCC	6.50e-20	9.00e-01	0.1327

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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
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:00097919	Esophagus	ESCC	post-embryonic development	56/8552	80/18723	9.08e-06	8.71e-05	56
GO:00485687	Esophagus	ESCC	embryonic organ development	228/8552	427/18723	7.28e-04	3.79e-03	228
GO:01201624	Esophagus	ESCC	positive regulation of cold-induced thermogenesis	57/8552	97/18723	6.43e-03	2.35e-02	57
GO:00485694	Esophagus	ESCC	post-embryonic animal organ development	12/8552	15/18723	7.31e-03	2.63e-02	12
GO:01061066	Esophagus	ESCC	cold-induced thermogenesis	80/8552	144/18723	1.07e-02	3.65e-02	80
GO:01201616	Esophagus	ESCC	regulation of cold-induced thermogenesis	80/8552	144/18723	1.07e-02	3.65e-02	80
GO:010610611	Liver	HCC	cold-induced thermogenesis	76/7958	144/18723	8.07e-03	3.18e-02	76
GO:012016111	Liver	HCC	regulation of cold-induced thermogenesis	76/7958	144/18723	8.07e-03	3.18e-02	76
GO:199084511	Liver	HCC	adaptive thermogenesis	81/7958	157/18723	1.32e-02	4.72e-02	81
GO:00097918	Oral cavity	OSCC	post-embryonic development	51/7305	80/18723	6.43e-06	7.13e-05	51
GO:00485693	Oral cavity	OSCC	post-embryonic animal organ development	13/7305	15/18723	2.07e-04	1.36e-03	13
GO:01061065	Oral cavity	OSCC	cold-induced thermogenesis	71/7305	144/18723	7.51e-03	2.75e-02	71
GO:01201615	Oral cavity	OSCC	regulation of cold-induced thermogenesis	71/7305	144/18723	7.51e-03	2.75e-02	71
GO:00016594	Oral cavity	OSCC	temperature homeostasis	84/7305	174/18723	7.84e-03	2.87e-02	84
GO:19908454	Oral cavity	OSCC	adaptive thermogenesis	76/7305	157/18723	1.02e-02	3.52e-02	76
GO:000979112	Oral cavity	LP	post-embryonic development	31/4623	80/18723	3.69e-03	2.44e-02	31
GO:004856911	Oral cavity	LP	post-embryonic animal organ development	9/4623	15/18723	3.82e-03	2.48e-02	9
GO:004856912	Skin	cSCC	post-embryonic animal organ development	10/4864	15/18723	1.10e-03	7.24e-03	10
GO:000979122	Skin	cSCC	post-embryonic development	32/4864	80/18723	4.18e-03	2.21e-02	32
GO:000979114	Thyroid	PTC	post-embryonic development	48/5968	80/18723	1.99e-07	3.56e-06	48

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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

MFAP2

SNV

Missense_Mutation

novel

c.409T>G

p.Cys137Gly

p.C137G

P55001

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MFAP2

SNV

Missense_Mutation

rs767651569

c.118G>A

p.Asp40Asn

p.D40N

P55001

protein_coding

deleterious_low_confidence(0.01)

benign(0.001)

TCGA-AZ-4315-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

MFAP2

SNV

Missense_Mutation

c.169N>T

p.Pro57Ser

p.P57S

P55001

protein_coding

tolerated_low_confidence(0.15)

benign(0)

TCGA-G4-6302-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

MFAP2

SNV

Missense_Mutation

rs759929375

c.305N>C

p.Tyr102Ser

p.Y102S

P55001

protein_coding

deleterious(0)

possibly_damaging(0.784)

TCGA-NH-A8F8-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Chemotherapy

fluorouracil

MFAP2

SNV

Missense_Mutation

novel

c.76N>A

p.Leu26Met

p.L26M

P55001

protein_coding

tolerated_low_confidence(0.16)

possibly_damaging(0.825)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

MFAP2

SNV

Missense_Mutation

c.427G>A

p.Ala143Thr

p.A143T

P55001

protein_coding

deleterious(0.01)

probably_damaging(0.975)

TCGA-AP-A051-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

MFAP2

SNV

Missense_Mutation

rs373562256

c.383G>A

p.Arg128His

p.R128H

P55001

protein_coding

deleterious(0.02)

probably_damaging(0.999)

TCGA-AP-A056-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

MFAP2

SNV

Missense_Mutation

c.308N>A

p.Pro103Gln

p.P103Q

P55001

protein_coding

deleterious(0)

probably_damaging(0.91)

TCGA-AP-A1DK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

MFAP2

SNV

Missense_Mutation

novel

c.209N>C

p.Val70Ala

p.V70A

P55001

protein_coding

tolerated(0.21)

benign(0.026)

TCGA-B5-A3FA-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

MFAP2

SNV

Missense_Mutation

novel

c.471N>A

p.Phe157Leu

p.F157L

P55001

protein_coding

deleterious_low_confidence(0.04)

benign(0.306)

TCGA-BS-A0UF-01

Endometrium

uterine corpus endometrioid carcinoma

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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