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: ZBTB20

Gene summary for ZBTB20

Gene summary.

Gene information	Species	Human
	Gene symbol	ZBTB20
	Gene ID	26137
	Gene name	zinc finger and BTB domain containing 20
	Gene Alias	DPZF
	Cytomap	3q13.31
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	Q9HC78

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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
26137	ZBTB20	GSM4909281	Human	Breast	IDC	3.82e-10	4.61e-01	0.21
26137	ZBTB20	GSM4909286	Human	Breast	IDC	4.32e-11	4.08e-01	0.1081
26137	ZBTB20	GSM4909290	Human	Breast	IDC	2.34e-05	-2.68e-01	0.2096
26137	ZBTB20	GSM4909296	Human	Breast	IDC	1.49e-05	-1.85e-01	0.1524
26137	ZBTB20	GSM4909297	Human	Breast	IDC	2.01e-04	-6.40e-02	0.1517
26137	ZBTB20	GSM4909299	Human	Breast	IDC	3.98e-26	7.28e-01	0.035
26137	ZBTB20	GSM4909300	Human	Breast	IDC	3.15e-06	4.94e-01	0.0334
26137	ZBTB20	GSM4909305	Human	Breast	IDC	1.36e-02	2.87e-01	0.0436
26137	ZBTB20	GSM4909307	Human	Breast	IDC	4.17e-04	3.72e-01	0.1569
26137	ZBTB20	GSM4909308	Human	Breast	IDC	1.84e-21	5.56e-01	0.158
26137	ZBTB20	GSM4909309	Human	Breast	IDC	1.37e-14	5.59e-01	0.0483
26137	ZBTB20	GSM4909311	Human	Breast	IDC	4.97e-13	-1.88e-01	0.1534
26137	ZBTB20	GSM4909312	Human	Breast	IDC	1.63e-06	-1.55e-01	0.1552
26137	ZBTB20	GSM4909313	Human	Breast	IDC	2.11e-08	4.20e-01	0.0391
26137	ZBTB20	GSM4909319	Human	Breast	IDC	3.98e-16	-2.64e-01	0.1563
26137	ZBTB20	GSM4909321	Human	Breast	IDC	1.17e-10	-1.82e-01	0.1559
26137	ZBTB20	brca1	Human	Breast	Precancer	5.56e-07	-2.68e-01	-0.0338
26137	ZBTB20	NCCBC14	Human	Breast	DCIS	6.81e-03	-1.17e-01	0.2021
26137	ZBTB20	NCCBC5	Human	Breast	DCIS	1.62e-02	-2.26e-01	0.2046
26137	ZBTB20	P1	Human	Breast	IDC	2.69e-06	9.61e-02	0.1527

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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
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
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
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:004346724	Oral cavity	EOLP	regulation of generation of precursor metabolites and energy	27/2218	130/18723	2.46e-03	1.50e-02	27
GO:000609125	Oral cavity	EOLP	generation of precursor metabolites and energy	79/2218	490/18723	2.65e-03	1.59e-02	79
GO:007132218	Oral cavity	EOLP	cellular response to carbohydrate stimulus	32/2218	163/18723	2.70e-03	1.62e-02	32
GO:004259317	Oral cavity	EOLP	glucose homeostasis	46/2218	258/18723	2.96e-03	1.74e-02	46
GO:003350017	Oral cavity	EOLP	carbohydrate homeostasis	46/2218	259/18723	3.20e-03	1.86e-02	46
GO:00061095	Oral cavity	EOLP	regulation of carbohydrate metabolic process	34/2218	178/18723	3.23e-03	1.88e-02	34
GO:00061107	Oral cavity	EOLP	regulation of glycolytic process	12/2218	45/18723	5.03e-03	2.65e-02	12
GO:001921614	Oral cavity	EOLP	regulation of lipid metabolic process	54/2218	331/18723	9.09e-03	4.15e-02	54
GO:19035808	Oral cavity	EOLP	positive regulation of ATP metabolic process	10/2218	38/18723	1.11e-02	4.88e-02	10
GO:000989633	Oral cavity	NEOLP	positive regulation of catabolic process	111/2005	492/18723	1.19e-14	4.72e-12	111
GO:003133133	Oral cavity	NEOLP	positive regulation of cellular catabolic process	97/2005	427/18723	3.77e-13	1.07e-10	97
GO:004603433	Oral cavity	NEOLP	ATP metabolic process	71/2005	277/18723	1.44e-12	3.17e-10	71
GO:000913532	Oral cavity	NEOLP	purine nucleoside diphosphate metabolic process	26/2005	103/18723	2.31e-05	3.72e-04	26
GO:000917932	Oral cavity	NEOLP	purine ribonucleoside diphosphate metabolic process	26/2005	103/18723	2.31e-05	3.72e-04	26
GO:000609133	Oral cavity	NEOLP	generation of precursor metabolites and energy	82/2005	490/18723	2.70e-05	4.22e-04	82
GO:000918532	Oral cavity	NEOLP	ribonucleoside diphosphate metabolic process	26/2005	106/18723	3.95e-05	5.62e-04	26
GO:000913232	Oral cavity	NEOLP	nucleoside diphosphate metabolic process	27/2005	124/18723	2.46e-04	2.54e-03	27
GO:000609624	Oral cavity	NEOLP	glycolytic process	20/2005	81/18723	2.69e-04	2.71e-03	20
GO:000675724	Oral cavity	NEOLP	ATP generation from ADP	20/2005	82/18723	3.21e-04	3.11e-03	20
GO:004693932	Oral cavity	NEOLP	nucleotide phosphorylation	23/2005	101/18723	3.50e-04	3.37e-03	23

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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

ZBTB20

SNV

Missense_Mutation

c.1090N>A

p.Glu364Lys

p.E364K

Q9HC78

protein_coding

deleterious(0.03)

probably_damaging(0.959)

TCGA-A8-A06Q-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

ZBTB20

SNV

Missense_Mutation

novel

c.1864A>G

p.Ile622Val

p.I622V

Q9HC78

protein_coding

tolerated(0.06)

possibly_damaging(0.727)

TCGA-AC-A62Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ZBTB20

SNV

Missense_Mutation

novel

c.1824C>G

p.Cys608Trp

p.C608W

Q9HC78

protein_coding

deleterious(0)

probably_damaging(0.973)

TCGA-B6-A0I5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ZBTB20

SNV

Missense_Mutation

c.1120A>C

p.Ser374Arg

p.S374R

Q9HC78

protein_coding

deleterious(0)

probably_damaging(0.969)

TCGA-BH-A18Q-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ZBTB20

SNV

Missense_Mutation

rs779910215

c.2155N>A

p.Val719Ile

p.V719I

Q9HC78

protein_coding

tolerated_low_confidence(0.1)

probably_damaging(0.984)

TCGA-D8-A1Y1-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

tamoxiphen

ZBTB20

insertion

Nonsense_Mutation

novel

c.1688_1689insAGAACGTTGCTTAAGATAAACTTTGCCTTCTTTGCAGGGTAATGTAA

p.Ala564GlufsTer6

p.A564Efs*6

Q9HC78

protein_coding

TCGA-A8-A08T-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

ZBTB20

insertion

Frame_Shift_Ins

novel

c.1171_1172insGATCTCGATGTCGCTGTAGCCA

p.Glu391GlyfsTer22

p.E391Gfs*22

Q9HC78

protein_coding

TCGA-AN-A0AS-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

ZBTB20

insertion

In_Frame_Ins

novel

c.1261_1262insATCCCCTTGCAACTGATGTCACCTGCAGCATGTCAA

p.Pro421delinsHisProLeuAlaThrAspValThrCysSerMetSerThr

p.P421delinsHPLATDVTCSMST

Q9HC78

protein_coding

TCGA-AO-A0JE-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

ZBTB20

insertion

Frame_Shift_Ins

novel

c.1822_1823insATATTCTTGTGGAAGAGAAAAAGAAAAAGAAATGGAGGGTGGGG

p.Cys608TyrfsTer25

p.C608Yfs*25

Q9HC78

protein_coding

TCGA-B6-A0I5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ZBTB20

deletion

Frame_Shift_Del

novel

c.284delN

p.Asn95ThrfsTer12

p.N95Tfs*12

Q9HC78

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

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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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