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: GATA3

Gene summary for GATA3

Gene summary.

Gene information	Species	Human
	Gene symbol	GATA3
	Gene ID	2625
	Gene name	GATA binding protein 3
	Gene Alias	HDR
	Cytomap	10p14
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	P23771

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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
2625	GATA3	GSM4909281	Human	Breast	IDC	1.06e-03	-2.69e-01	0.21
2625	GATA3	GSM4909282	Human	Breast	IDC	2.38e-09	-3.93e-01	-0.0288
2625	GATA3	GSM4909286	Human	Breast	IDC	1.62e-06	-3.67e-01	0.1081
2625	GATA3	GSM4909291	Human	Breast	IDC	2.51e-28	8.19e-01	0.1753
2625	GATA3	GSM4909293	Human	Breast	IDC	1.38e-61	1.01e+00	0.1581
2625	GATA3	GSM4909295	Human	Breast	IDC	7.12e-03	-3.97e-01	0.0898
2625	GATA3	GSM4909296	Human	Breast	IDC	6.20e-04	2.86e-01	0.1524
2625	GATA3	GSM4909297	Human	Breast	IDC	1.83e-42	7.34e-01	0.1517
2625	GATA3	GSM4909298	Human	Breast	IDC	3.79e-86	1.17e+00	0.1551
2625	GATA3	GSM4909301	Human	Breast	IDC	9.33e-133	1.45e+00	0.1577
2625	GATA3	GSM4909302	Human	Breast	IDC	4.11e-22	6.50e-01	0.1545
2625	GATA3	GSM4909303	Human	Breast	IDC	1.26e-03	4.95e-01	0.0438
2625	GATA3	GSM4909304	Human	Breast	IDC	3.37e-24	6.01e-01	0.1636
2625	GATA3	GSM4909305	Human	Breast	IDC	1.77e-10	5.03e-01	0.0436
2625	GATA3	GSM4909306	Human	Breast	IDC	2.05e-41	8.77e-01	0.1564
2625	GATA3	GSM4909307	Human	Breast	IDC	1.85e-38	8.60e-01	0.1569
2625	GATA3	GSM4909308	Human	Breast	IDC	1.52e-99	1.25e+00	0.158
2625	GATA3	GSM4909311	Human	Breast	IDC	2.09e-18	1.77e-01	0.1534
2625	GATA3	GSM4909312	Human	Breast	IDC	6.04e-21	6.48e-01	0.1552
2625	GATA3	GSM4909313	Human	Breast	IDC	2.33e-04	2.88e-01	0.0391

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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
Prostate		BPH: Benign Prostatic Hyperplasia
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ

∗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:007135312	Prostate	Tumor	cellular response to interleukin-4	13/3246	33/18723	2.26e-03	1.28e-02	13
GO:003106011	Prostate	Tumor	regulation of histone methylation	22/3246	69/18723	2.31e-03	1.30e-02	22
GO:004240111	Prostate	Tumor	cellular biogenic amine biosynthetic process	14/3246	37/18723	2.43e-03	1.36e-02	14
GO:004663411	Prostate	Tumor	regulation of alpha-beta T cell activation	30/3246	104/18723	2.48e-03	1.38e-02	30
GO:004853811	Prostate	Tumor	thymus development	16/3246	45/18723	2.59e-03	1.43e-02	16
GO:007200913	Prostate	Tumor	nephron epithelium development	31/3246	109/18723	2.70e-03	1.48e-02	31
GO:004352315	Prostate	Tumor	regulation of neuron apoptotic process	53/3246	212/18723	2.92e-03	1.58e-02	53
GO:004561911	Prostate	Tumor	regulation of lymphocyte differentiation	45/3246	174/18723	2.93e-03	1.58e-02	45
GO:000300711	Prostate	Tumor	heart morphogenesis	60/3246	246/18723	2.99e-03	1.61e-02	60
GO:004663111	Prostate	Tumor	alpha-beta T cell activation	41/3246	156/18723	3.21e-03	1.68e-02	41
GO:000930911	Prostate	Tumor	amine biosynthetic process	14/3246	38/18723	3.24e-03	1.69e-02	14
GO:190210712	Prostate	Tumor	positive regulation of leukocyte differentiation	41/3246	157/18723	3.63e-03	1.86e-02	41
GO:190370812	Prostate	Tumor	positive regulation of hemopoiesis	41/3246	157/18723	3.63e-03	1.86e-02	41
GO:000165612	Prostate	Tumor	metanephros development	25/3246	85/18723	4.12e-03	2.08e-02	25
GO:00323501	Prostate	Tumor	regulation of hormone metabolic process	13/3246	35/18723	4.14e-03	2.08e-02	13
GO:000320611	Prostate	Tumor	cardiac chamber morphogenesis	33/3246	121/18723	4.16e-03	2.09e-02	33
GO:000327911	Prostate	Tumor	cardiac septum development	29/3246	103/18723	4.26e-03	2.13e-02	29
GO:003021711	Prostate	Tumor	T cell differentiation	61/3246	257/18723	5.30e-03	2.54e-02	61
GO:000165712	Prostate	Tumor	ureteric bud development	26/3246	91/18723	5.32e-03	2.54e-02	26
GO:007208013	Prostate	Tumor	nephron tubule development	26/3246	91/18723	5.32e-03	2.54e-02	26

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa046597	Prostate	BPH	Th17 cell differentiation	36/1718	108/8465	9.75e-04	4.47e-03	2.76e-03	36
hsa0492814	Prostate	BPH	Parathyroid hormone synthesis, secretion and action	33/1718	106/8465	5.30e-03	1.75e-02	1.08e-02	33
hsa0465912	Prostate	BPH	Th17 cell differentiation	36/1718	108/8465	9.75e-04	4.47e-03	2.76e-03	36
hsa0492815	Prostate	BPH	Parathyroid hormone synthesis, secretion and action	33/1718	106/8465	5.30e-03	1.75e-02	1.08e-02	33
hsa0465922	Prostate	Tumor	Th17 cell differentiation	36/1791	108/8465	2.11e-03	8.42e-03	5.22e-03	36
hsa0492822	Prostate	Tumor	Parathyroid hormone synthesis, secretion and action	35/1791	106/8465	2.89e-03	1.07e-02	6.67e-03	35
hsa0465932	Prostate	Tumor	Th17 cell differentiation	36/1791	108/8465	2.11e-03	8.42e-03	5.22e-03	36
hsa0492832	Prostate	Tumor	Parathyroid hormone synthesis, secretion and action	35/1791	106/8465	2.89e-03	1.07e-02	6.67e-03	35

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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
GATA3	BMEM	Breast	IDC	COX6C,AGR3,DHRS2, etc.	7.79e-02
GATA3	FIB	Breast	DCIS	SMIM22,COX6C,TSTD1, etc.	7.41e-01
GATA3	FIB	Breast	IDC	SMIM22,COX6C,TSTD1, etc.	2.61e-01
GATA3	KER	Cervix	ADJ	KCTD12,RSPO3,DHX58, etc.	4.44e-16
GATA3	BAS	Cervix	ADJ	KCTD12,RSPO3,DHX58, etc.	0.00e+00
GATA3	COL	Cervix	ADJ	KCTD12,RSPO3,DHX58, etc.	0.00e+00
GATA3	KER	Cervix	HSIL_HPV	KCTD12,RSPO3,DHX58, etc.	1.32e-02
GATA3	MES	Cervix	N_HPV	KCTD12,RSPO3,DHX58, etc.	7.05e-03
GATA3	CD8TRM	Cervix	ADJ	IL2RB,B3GNT7,KRT86, etc.	2.98e-01
GATA3	CD8TRM	Cervix	CC	IL2RB,B3GNT7,KRT86, etc.	1.62e-01

∗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

GATA3

SNV

Missense_Mutation

c.881T>A

p.Met294Lys

p.M294K

P23771

protein_coding

deleterious(0)

possibly_damaging(0.692)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

GATA3

SNV

Missense_Mutation

c.1095N>T

p.Arg365Ser

p.R365S

P23771

protein_coding

deleterious(0.04)

probably_damaging(1)

TCGA-AR-A0U2-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

tamoxiphen

GATA3

SNV

Missense_Mutation

c.983N>A

p.Leu328His

p.L328H

P23771

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AR-A24P-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

GATA3

SNV

Missense_Mutation

novel

c.989G>A

p.Arg330Lys

p.R330K

P23771

protein_coding

deleterious(0.01)

probably_damaging(1)

TCGA-B6-A40C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

cyclophosphamide

GATA3

SNV

Missense_Mutation

c.1071G>T

p.Met357Ile

p.M357I

P23771

protein_coding

deleterious(0.01)

probably_damaging(0.925)

TCGA-BH-A0BQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

GATA3

SNV

Missense_Mutation

novel

c.992N>A

p.Arg331Lys

p.R331K

P23771

protein_coding

deleterious(0.04)

probably_damaging(0.946)

TCGA-BH-A0C7-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

GATA3

SNV

Missense_Mutation

c.881N>A

p.Met294Lys

p.M294K

P23771

protein_coding

deleterious(0)

possibly_damaging(0.692)

TCGA-BH-A0H5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

GATA3

SNV

Missense_Mutation

c.845N>G

p.His282Arg

p.H282R

P23771

protein_coding

deleterious(0)

possibly_damaging(0.882)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

GATA3

SNV

Missense_Mutation

c.881N>A

p.Met294Lys

p.M294K

P23771

protein_coding

deleterious(0)

possibly_damaging(0.692)

TCGA-BH-A0HP-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

doxorubicin

GATA3

SNV

Missense_Mutation

c.356A>T

p.Lys119Met

p.K119M

P23771

protein_coding

deleterious(0)

probably_damaging(0.936)

TCGA-BH-A18M-01

Breast

breast invasive carcinoma

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
2625	GATA3	CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR		mercaptopurine	MERCAPTOPURINE	24141364
2625	GATA3	CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR		pegaspargase	PEGASPARGASE	24141364
2625	GATA3	CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR		leucovorin	LEUCOVORIN	24141364
2625	GATA3	CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR		vincristine	VINCRISTINE	24141364
2625	GATA3	CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR		thioguanine	THIOGUANINE	24141364
2625	GATA3	CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR		asparaginase	ASPARAGINASE	24141364
2625	GATA3	CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR		prednisone	PREDNISONE	24141364
2625	GATA3	CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR		methotrexate	METHOTREXATE	24141364
2625	GATA3	CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR		dexamethasone	DEXAMETHASONE	24141364
2625	GATA3	CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR		doxorubicin	DOXORUBICIN	24141364

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