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: MEF2A

Gene summary for MEF2A

Gene summary.

Gene information	Species	Human
	Gene symbol	MEF2A
	Gene ID	4205
	Gene name	myocyte enhancer factor 2A
	Gene Alias	ADCAD1
	Cytomap	15q26.3
	Gene Type	protein-coding
	GO ID	GO:0000002
	UniProtAcc	A0A0S2Z417

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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
4205	MEF2A	CA_HPV_1	Human	Cervix	CC	5.54e-05	2.45e-01	0.0264
4205	MEF2A	CA_HPV_3	Human	Cervix	CC	3.55e-04	1.00e-01	0.0414
4205	MEF2A	CCI_2	Human	Cervix	CC	3.16e-09	1.27e+00	0.5249
4205	MEF2A	CCI_3	Human	Cervix	CC	1.64e-08	8.44e-01	0.516
4205	MEF2A	HTA11_3410_2000001011	Human	Colorectum	AD	2.06e-16	-5.78e-01	0.0155
4205	MEF2A	HTA11_2951_2000001011	Human	Colorectum	AD	5.49e-04	-8.41e-01	0.0216
4205	MEF2A	HTA11_3361_2000001011	Human	Colorectum	AD	1.95e-04	-5.76e-01	-0.1207
4205	MEF2A	HTA11_866_2000001011	Human	Colorectum	AD	3.57e-02	-2.52e-01	-0.1001
4205	MEF2A	HTA11_5212_2000001011	Human	Colorectum	AD	1.65e-02	-5.74e-01	-0.2061
4205	MEF2A	HTA11_7862_2000001011	Human	Colorectum	AD	4.61e-02	-5.36e-01	-0.0179
4205	MEF2A	HTA11_866_3004761011	Human	Colorectum	AD	1.09e-12	-6.63e-01	0.096
4205	MEF2A	HTA11_4255_2000001011	Human	Colorectum	SER	4.09e-02	-7.12e-01	0.0446
4205	MEF2A	HTA11_8622_2000001021	Human	Colorectum	SER	5.34e-04	-6.70e-01	0.0528
4205	MEF2A	HTA11_10711_2000001011	Human	Colorectum	AD	7.38e-04	-5.12e-01	0.0338
4205	MEF2A	HTA11_7696_3000711011	Human	Colorectum	AD	1.27e-18	-5.17e-01	0.0674
4205	MEF2A	HTA11_99999970781_79442	Human	Colorectum	MSS	7.64e-19	-4.94e-01	0.294
4205	MEF2A	HTA11_99999971662_82457	Human	Colorectum	MSS	8.09e-24	-6.57e-01	0.3859
4205	MEF2A	HTA11_99999973899_84307	Human	Colorectum	MSS	1.41e-05	-6.62e-01	0.2585
4205	MEF2A	HTA11_99999974143_84620	Human	Colorectum	MSS	9.36e-31	-6.97e-01	0.3005
4205	MEF2A	F007	Human	Colorectum	FAP	2.39e-02	-3.89e-01	0.1176

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
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
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
Prostate		BPH: Benign Prostatic Hyperplasia
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:00163587	Cervix	CC	dendrite development	58/2311	243/18723	4.52e-07	1.76e-05	58
GO:00605375	Cervix	CC	muscle tissue development	76/2311	403/18723	9.76e-05	1.27e-03	76
GO:00310329	Cervix	CC	actomyosin structure organization	43/2311	196/18723	1.11e-04	1.40e-03	43
GO:00147064	Cervix	CC	striated muscle tissue development	72/2311	384/18723	1.76e-04	2.07e-03	72
GO:00426924	Cervix	CC	muscle cell differentiation	69/2311	384/18723	8.12e-04	7.09e-03	69
GO:001003810	Cervix	CC	response to metal ion	67/2311	373/18723	9.67e-04	8.10e-03	67
GO:00515926	Cervix	CC	response to calcium ion	31/2311	149/18723	2.31e-03	1.65e-02	31
GO:00075173	Cervix	CC	muscle organ development	58/2311	327/18723	2.73e-03	1.85e-02	58
GO:00488135	Cervix	CC	dendrite morphogenesis	30/2311	146/18723	3.27e-03	2.13e-02	30
GO:00148963	Cervix	CC	muscle hypertrophy	23/2311	104/18723	3.63e-03	2.32e-02	23
GO:00511464	Cervix	CC	striated muscle cell differentiation	50/2311	283/18723	5.53e-03	3.19e-02	50
GO:00148972	Cervix	CC	striated muscle hypertrophy	22/2311	102/18723	5.99e-03	3.42e-02	22
GO:00516461	Cervix	CC	mitochondrion localization	13/2311	50/18723	6.42e-03	3.58e-02	13
GO:00902578	Cervix	CC	regulation of muscle system process	45/2311	252/18723	6.73e-03	3.70e-02	45
GO:00347645	Cervix	CC	positive regulation of transmembrane transport	40/2311	219/18723	6.97e-03	3.76e-02	40
GO:00435024	Cervix	CC	regulation of muscle adaptation	21/2311	98/18723	7.71e-03	4.09e-02	21
GO:00033003	Cervix	CC	cardiac muscle hypertrophy	21/2311	99/18723	8.67e-03	4.46e-02	21
GO:0031032	Colorectum	AD	actomyosin structure organization	65/3918	196/18723	4.17e-05	7.37e-04	65
GO:0010038	Colorectum	AD	response to metal ion	106/3918	373/18723	3.22e-04	3.83e-03	106
GO:0071248	Colorectum	AD	cellular response to metal ion	61/3918	197/18723	5.74e-04	6.09e-03	61

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0541820	Cervix	CC	Fluid shear stress and atherosclerosis	50/1267	139/8465	5.71e-10	1.32e-08	7.81e-09	50
hsa0492812	Cervix	CC	Parathyroid hormone synthesis, secretion and action	27/1267	106/8465	3.12e-03	1.19e-02	7.03e-03	27
hsa05418110	Cervix	CC	Fluid shear stress and atherosclerosis	50/1267	139/8465	5.71e-10	1.32e-08	7.81e-09	50
hsa0492813	Cervix	CC	Parathyroid hormone synthesis, secretion and action	27/1267	106/8465	3.12e-03	1.19e-02	7.03e-03	27
hsa05418	Colorectum	AD	Fluid shear stress and atherosclerosis	54/2092	139/8465	1.41e-04	1.16e-03	7.37e-04	54
hsa04928	Colorectum	AD	Parathyroid hormone synthesis, secretion and action	38/2092	106/8465	6.60e-03	2.77e-02	1.76e-02	38
hsa054181	Colorectum	AD	Fluid shear stress and atherosclerosis	54/2092	139/8465	1.41e-04	1.16e-03	7.37e-04	54
hsa049281	Colorectum	AD	Parathyroid hormone synthesis, secretion and action	38/2092	106/8465	6.60e-03	2.77e-02	1.76e-02	38
hsa054182	Colorectum	SER	Fluid shear stress and atherosclerosis	40/1580	139/8465	2.28e-03	1.75e-02	1.27e-02	40
hsa049282	Colorectum	SER	Parathyroid hormone synthesis, secretion and action	31/1580	106/8465	5.20e-03	3.28e-02	2.38e-02	31
hsa054183	Colorectum	SER	Fluid shear stress and atherosclerosis	40/1580	139/8465	2.28e-03	1.75e-02	1.27e-02	40
hsa049283	Colorectum	SER	Parathyroid hormone synthesis, secretion and action	31/1580	106/8465	5.20e-03	3.28e-02	2.38e-02	31
hsa054184	Colorectum	MSS	Fluid shear stress and atherosclerosis	51/1875	139/8465	6.06e-05	5.80e-04	3.55e-04	51
hsa049284	Colorectum	MSS	Parathyroid hormone synthesis, secretion and action	37/1875	106/8465	1.72e-03	9.13e-03	5.59e-03	37
hsa04022	Colorectum	MSS	cGMP-PKG signaling pathway	51/1875	167/8465	6.83e-03	2.73e-02	1.67e-02	51
hsa054185	Colorectum	MSS	Fluid shear stress and atherosclerosis	51/1875	139/8465	6.06e-05	5.80e-04	3.55e-04	51
hsa049285	Colorectum	MSS	Parathyroid hormone synthesis, secretion and action	37/1875	106/8465	1.72e-03	9.13e-03	5.59e-03	37
hsa040221	Colorectum	MSS	cGMP-PKG signaling pathway	51/1875	167/8465	6.83e-03	2.73e-02	1.67e-02	51
hsa054188	Colorectum	FAP	Fluid shear stress and atherosclerosis	45/1404	139/8465	3.05e-06	4.63e-05	2.81e-05	45
hsa040222	Colorectum	FAP	cGMP-PKG signaling pathway	42/1404	167/8465	2.84e-03	1.27e-02	7.70e-03	42

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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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
MEF2A	LYMEND	Breast	ADJ	SPAG9,MALAT1,ANKRD12, etc.	6.07e-02
MEF2A	PVA	Breast	Healthy	SPAG9,MALAT1,ANKRD12, etc.	2.41e-01
MEF2A	MVA	Breast	Healthy	SPAG9,MALAT1,ANKRD12, etc.	1.50e-01
MEF2A	GLAN	Endometrium	Healthy	GNAO1,CLASP2,ABI3BP, etc.	5.88e-01
MEF2A	BMEM	Endometrium	EEC	LASP1,PLXDC2,PALD1, etc.	1.25e-01
MEF2A	MVA	Esophagus	ADJ	PAK1,IGF1R,TM2D3, etc.	1.90e-01
MEF2A	MVA	Esophagus	ESCC	PAK1,IGF1R,TM2D3, etc.	3.34e-01
MEF2A	MVA	Esophagus	Healthy	PAK1,IGF1R,TM2D3, etc.	3.39e-02
MEF2A	LC	Lung	ADJ	PLXDC2,CAMK1D,C20orf194, etc.	2.02e-01
MEF2A	cDC	Lung	ADJ	PLXDC2,CAMK1D,C20orf194, etc.	3.13e-02

∗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

MEF2A

SNV

Missense_Mutation

c.316G>C

p.Glu106Gln

p.E106Q

Q02078

protein_coding

tolerated(0.4)

benign(0.033)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MEF2A

SNV

Missense_Mutation

c.1052T>C

p.Phe351Ser

p.F351S

Q02078

protein_coding

deleterious(0.02)

probably_damaging(0.991)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MEF2A

SNV

Missense_Mutation

c.58A>T

p.Thr20Ser

p.T20S

Q02078

protein_coding

deleterious(0)

possibly_damaging(0.746)

TCGA-C8-A26Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MEF2A

SNV

Missense_Mutation

rs553844161

c.245C>T

p.Ser82Leu

p.S82L

Q02078

protein_coding

deleterious(0.01)

probably_damaging(0.962)

TCGA-E2-A14W-01

Breast

breast invasive carcinoma

Male

>=65

I/II

Chemotherapy

cytoxan

MEF2A

SNV

Missense_Mutation

c.955A>G

p.Ser319Gly

p.S319G

Q02078

protein_coding

deleterious(0.02)

probably_damaging(0.981)

TCGA-E9-A1N5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

MEF2A

deletion

In_Frame_Del

novel

c.1277_1288delAGCAGCAGCCGC

p.Gln426_Pro429del

p.Q426_P429del

Q02078

protein_coding

TCGA-A2-A3XS-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

MEF2A

insertion

In_Frame_Ins

novel

c.981_982insTATGTT

p.Tyr327_Ser328insTyrVal

p.Y327_S328insYV

Q02078

protein_coding

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

MEF2A

insertion

Nonsense_Mutation

novel

c.983_984insTTAGCATGGACAAAGGTTAAG

p.Ser328_Ala329insTer

p.S328_A329ins*

Q02078

protein_coding

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

MEF2A

deletion

Frame_Shift_Del

c.705delN

p.Leu236Ter

p.L236*

Q02078

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

MEF2A

SNV

Missense_Mutation

c.698C>T

p.Ser233Phe

p.S233F

Q02078

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-IR-A3LH-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

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