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: MBD2

Gene summary for MBD2

Gene summary.

Gene information	Species	Human
	Gene symbol	MBD2
	Gene ID	8932
	Gene name	methyl-CpG binding domain protein 2
	Gene Alias	DMTase
	Cytomap	18q21.2
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	Q9UBB5

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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
8932	MBD2	CA_HPV_1	Human	Cervix	CC	3.66e-02	8.06e-02	0.0264
8932	MBD2	CA_HPV_2	Human	Cervix	CC	2.08e-04	3.06e-01	0.0391
8932	MBD2	N_HPV_2	Human	Cervix	N_HPV	2.03e-05	2.24e-01	-0.0131
8932	MBD2	CCI_1	Human	Cervix	CC	5.30e-05	8.77e-01	0.528
8932	MBD2	CCI_3	Human	Cervix	CC	2.28e-04	6.65e-01	0.516
8932	MBD2	Tumor	Human	Cervix	CC	5.39e-03	2.65e-01	0.1241
8932	MBD2	sample3	Human	Cervix	CC	8.23e-13	3.81e-01	0.1387
8932	MBD2	T3	Human	Cervix	CC	4.56e-15	3.79e-01	0.1389
8932	MBD2	HTA11_3410_2000001011	Human	Colorectum	AD	2.21e-12	-3.40e-01	0.0155
8932	MBD2	HTA11_347_2000001011	Human	Colorectum	AD	5.15e-04	4.09e-01	-0.1954
8932	MBD2	HTA11_866_3004761011	Human	Colorectum	AD	8.04e-03	-3.28e-01	0.096
8932	MBD2	HTA11_7696_3000711011	Human	Colorectum	AD	1.43e-04	-2.41e-01	0.0674
8932	MBD2	HTA11_99999974143_84620	Human	Colorectum	MSS	3.21e-07	-3.75e-01	0.3005
8932	MBD2	A001-C-207	Human	Colorectum	FAP	1.74e-04	-2.92e-01	0.1278
8932	MBD2	A015-C-203	Human	Colorectum	FAP	9.13e-27	-5.26e-01	-0.1294
8932	MBD2	A015-C-204	Human	Colorectum	FAP	3.11e-07	-2.89e-01	-0.0228
8932	MBD2	A014-C-040	Human	Colorectum	FAP	1.94e-05	-4.63e-01	-0.1184
8932	MBD2	A002-C-201	Human	Colorectum	FAP	5.11e-19	-4.59e-01	0.0324
8932	MBD2	A002-C-203	Human	Colorectum	FAP	1.14e-03	-1.55e-01	0.2786
8932	MBD2	A001-C-119	Human	Colorectum	FAP	2.31e-06	-3.38e-01	-0.1557

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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
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
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:005109828	Thyroid	HT	regulation of binding	56/1272	363/18723	6.41e-09	5.75e-07	56
GO:005109928	Thyroid	HT	positive regulation of binding	34/1272	173/18723	1.64e-08	1.30e-06	34
GO:000756828	Thyroid	HT	aging	46/1272	339/18723	5.52e-06	1.68e-04	46
GO:003166729	Thyroid	HT	response to nutrient levels	56/1272	474/18723	3.66e-05	7.57e-04	56
GO:000961219	Thyroid	HT	response to mechanical stimulus	28/1272	216/18723	7.49e-04	8.32e-03	28
GO:001605520	Thyroid	HT	Wnt signaling pathway	48/1272	444/18723	9.68e-04	9.93e-03	48
GO:019873820	Thyroid	HT	cell-cell signaling by wnt	48/1272	446/18723	1.07e-03	1.07e-02	48
GO:003011120	Thyroid	HT	regulation of Wnt signaling pathway	35/1272	328/18723	5.41e-03	3.58e-02	35
GO:0051098113	Thyroid	PTC	regulation of binding	195/5968	363/18723	3.21e-18	3.37e-16	195
GO:0016055110	Thyroid	PTC	Wnt signaling pathway	217/5968	444/18723	3.71e-14	2.30e-12	217
GO:0198738110	Thyroid	PTC	cell-cell signaling by wnt	217/5968	446/18723	6.68e-14	3.73e-12	217
GO:0051099113	Thyroid	PTC	positive regulation of binding	100/5968	173/18723	1.56e-12	6.96e-11	100
GO:0030111110	Thyroid	PTC	regulation of Wnt signaling pathway	163/5968	328/18723	1.05e-11	4.29e-10	163
GO:005105218	Thyroid	PTC	regulation of DNA metabolic process	171/5968	359/18723	2.52e-10	8.33e-09	171
GO:000632520	Thyroid	PTC	chromatin organization	183/5968	409/18723	2.55e-08	5.70e-07	183
GO:0007568111	Thyroid	PTC	aging	153/5968	339/18723	1.80e-07	3.34e-06	153
GO:0031667113	Thyroid	PTC	response to nutrient levels	201/5968	474/18723	7.00e-07	1.10e-05	201
GO:003017719	Thyroid	PTC	positive regulation of Wnt signaling pathway	72/5968	140/18723	1.16e-06	1.69e-05	72
GO:00400297	Thyroid	PTC	regulation of gene expression, epigenetic	57/5968	105/18723	1.60e-06	2.25e-05	57
GO:0009612110	Thyroid	PTC	response to mechanical stimulus	98/5968	216/18723	2.09e-05	2.09e-04	98

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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

MBD2

deletion

Frame_Shift_Del

novel

c.904delN

p.Thr302ProfsTer86

p.T302Pfs*86

Q9UBB5

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

MBD2

SNV

Missense_Mutation

rs780879642

c.1207N>G

p.Ile403Val

p.I403V

Q9UBB5

protein_coding

tolerated_low_confidence(0.15)

benign(0)

TCGA-AA-3811-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

MBD2

SNV

Missense_Mutation

novel

c.530N>C

p.Val177Ala

p.V177A

Q9UBB5

protein_coding

deleterious(0)

probably_damaging(0.959)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

MBD2

SNV

Missense_Mutation

rs745860253

c.677N>A

p.Arg226Gln

p.R226Q

Q9UBB5

protein_coding

tolerated(0.18)

benign(0.372)

TCGA-AG-3892-01

Colorectum

rectum adenocarcinoma

Female

<65

I/II

Unknown

MBD2

SNV

Missense_Mutation

novel

c.836N>A

p.Arg279His

p.R279H

Q9UBB5

protein_coding

tolerated(0.08)

benign(0.16)

TCGA-AJ-A3EK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

MBD2

SNV

Missense_Mutation

c.1190N>G

p.Asp397Gly

p.D397G

Q9UBB5

protein_coding

deleterious_low_confidence(0.02)

benign(0.374)

TCGA-AP-A051-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

MBD2

SNV

Missense_Mutation

novel

c.781N>C

p.Asn261His

p.N261H

Q9UBB5

protein_coding

deleterious(0.03)

benign(0.41)

TCGA-AP-A1DV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

MBD2

SNV

Missense_Mutation

novel

c.1201A>C

p.Met401Leu

p.M401L

Q9UBB5

protein_coding

tolerated_low_confidence(0.26)

benign(0)

TCGA-AX-A05Z-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

MBD2

SNV

Missense_Mutation

novel

c.1081N>T

p.Ala361Ser

p.A361S

Q9UBB5

protein_coding

tolerated(0.09)

benign(0.326)

TCGA-AX-A06F-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatin

MBD2

SNV

Missense_Mutation

rs745860253

c.677G>A

p.Arg226Gln

p.R226Q

Q9UBB5

protein_coding

tolerated(0.18)

benign(0.372)

TCGA-AX-A2HC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

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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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