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: MGST3

Gene summary for MGST3

Gene summary.

Gene information	Species	Human
	Gene symbol	MGST3
	Gene ID	4259
	Gene name	microsomal glutathione S-transferase 3
	Gene Alias	GST-III
	Cytomap	1q24.1
	Gene Type	protein-coding
	GO ID	GO:0006082
	UniProtAcc	A0A024R8Z1

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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
4259	MGST3	GSM4909281	Human	Breast	IDC	2.19e-24	6.49e-01	0.21
4259	MGST3	GSM4909282	Human	Breast	IDC	1.44e-35	6.99e-01	-0.0288
4259	MGST3	GSM4909285	Human	Breast	IDC	1.47e-61	9.03e-01	0.21
4259	MGST3	GSM4909286	Human	Breast	IDC	5.39e-05	1.16e-01	0.1081
4259	MGST3	GSM4909287	Human	Breast	IDC	6.80e-09	3.96e-01	0.2057
4259	MGST3	GSM4909288	Human	Breast	IDC	1.07e-04	3.70e-01	0.0988
4259	MGST3	GSM4909293	Human	Breast	IDC	1.00e-40	7.74e-01	0.1581
4259	MGST3	GSM4909294	Human	Breast	IDC	4.14e-07	-2.09e-02	0.2022
4259	MGST3	GSM4909296	Human	Breast	IDC	1.30e-07	1.24e-01	0.1524
4259	MGST3	GSM4909297	Human	Breast	IDC	6.01e-13	8.18e-02	0.1517
4259	MGST3	GSM4909298	Human	Breast	IDC	8.45e-04	2.00e-01	0.1551
4259	MGST3	GSM4909301	Human	Breast	IDC	4.71e-48	8.22e-01	0.1577
4259	MGST3	GSM4909302	Human	Breast	IDC	1.00e-11	4.49e-01	0.1545
4259	MGST3	GSM4909304	Human	Breast	IDC	4.04e-05	4.05e-01	0.1636
4259	MGST3	GSM4909306	Human	Breast	IDC	5.11e-15	5.47e-01	0.1564
4259	MGST3	GSM4909307	Human	Breast	IDC	3.72e-20	5.78e-01	0.1569
4259	MGST3	GSM4909308	Human	Breast	IDC	3.03e-28	6.22e-01	0.158
4259	MGST3	GSM4909311	Human	Breast	IDC	2.85e-32	-2.67e-01	0.1534
4259	MGST3	GSM4909312	Human	Breast	IDC	2.50e-08	2.49e-02	0.1552
4259	MGST3	GSM4909315	Human	Breast	IDC	5.79e-23	5.86e-01	0.21

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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
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:00988698	Breast	Precancer	cellular oxidant detoxification	20/1080	101/18723	1.07e-06	4.18e-05	20
GO:19907488	Breast	Precancer	cellular detoxification	21/1080	116/18723	2.67e-06	8.89e-05	21
GO:00987548	Breast	Precancer	detoxification	24/1080	152/18723	6.49e-06	1.81e-04	24
GO:00972378	Breast	Precancer	cellular response to toxic substance	21/1080	124/18723	7.98e-06	2.17e-04	21
GO:00096368	Breast	Precancer	response to toxic substance	31/1080	262/18723	1.18e-04	2.12e-03	31
GO:00463946	Breast	Precancer	carboxylic acid biosynthetic process	32/1080	314/18723	1.30e-03	1.38e-02	32
GO:00160536	Breast	Precancer	organic acid biosynthetic process	32/1080	316/18723	1.44e-03	1.50e-02	32
GO:000963613	Breast	IDC	response to toxic substance	44/1434	262/18723	6.33e-07	3.00e-05	44
GO:009875413	Breast	IDC	detoxification	29/1434	152/18723	3.97e-06	1.43e-04	29
GO:009886913	Breast	IDC	cellular oxidant detoxification	22/1434	101/18723	6.31e-06	1.98e-04	22
GO:199074813	Breast	IDC	cellular detoxification	23/1434	116/18723	2.02e-05	4.92e-04	23
GO:009723713	Breast	IDC	cellular response to toxic substance	24/1434	124/18723	2.05e-05	4.97e-04	24
GO:001605313	Breast	IDC	organic acid biosynthetic process	39/1434	316/18723	2.13e-03	1.99e-02	39
GO:004639413	Breast	IDC	carboxylic acid biosynthetic process	38/1434	314/18723	3.39e-03	2.83e-02	38
GO:000963623	Breast	DCIS	response to toxic substance	42/1390	262/18723	1.76e-06	6.56e-05	42
GO:009875423	Breast	DCIS	detoxification	29/1390	152/18723	2.15e-06	7.79e-05	29
GO:009886923	Breast	DCIS	cellular oxidant detoxification	22/1390	101/18723	3.82e-06	1.16e-04	22
GO:199074823	Breast	DCIS	cellular detoxification	23/1390	116/18723	1.22e-05	3.12e-04	23
GO:009723723	Breast	DCIS	cellular response to toxic substance	24/1390	124/18723	1.22e-05	3.12e-04	24
GO:001605322	Breast	DCIS	organic acid biosynthetic process	38/1390	316/18723	2.22e-03	2.04e-02	38

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0520818	Breast	Precancer	Chemical carcinogenesis - reactive oxygen species	68/684	223/8465	3.61e-23	1.14e-21	8.73e-22	68
hsa0541818	Breast	Precancer	Fluid shear stress and atherosclerosis	28/684	139/8465	4.74e-06	6.00e-05	4.59e-05	28
hsa0048010	Breast	Precancer	Glutathione metabolism	12/684	57/8465	1.68e-03	1.08e-02	8.30e-03	12
hsa0520819	Breast	Precancer	Chemical carcinogenesis - reactive oxygen species	68/684	223/8465	3.61e-23	1.14e-21	8.73e-22	68
hsa0541819	Breast	Precancer	Fluid shear stress and atherosclerosis	28/684	139/8465	4.74e-06	6.00e-05	4.59e-05	28
hsa0048013	Breast	Precancer	Glutathione metabolism	12/684	57/8465	1.68e-03	1.08e-02	8.30e-03	12
hsa0520824	Breast	IDC	Chemical carcinogenesis - reactive oxygen species	71/867	223/8465	2.55e-19	7.53e-18	5.63e-18	71
hsa0541824	Breast	IDC	Fluid shear stress and atherosclerosis	34/867	139/8465	9.41e-07	1.61e-05	1.20e-05	34
hsa0048023	Breast	IDC	Glutathione metabolism	13/867	57/8465	4.25e-03	2.56e-02	1.91e-02	13
hsa0520834	Breast	IDC	Chemical carcinogenesis - reactive oxygen species	71/867	223/8465	2.55e-19	7.53e-18	5.63e-18	71
hsa0541834	Breast	IDC	Fluid shear stress and atherosclerosis	34/867	139/8465	9.41e-07	1.61e-05	1.20e-05	34
hsa0048033	Breast	IDC	Glutathione metabolism	13/867	57/8465	4.25e-03	2.56e-02	1.91e-02	13
hsa0520843	Breast	DCIS	Chemical carcinogenesis - reactive oxygen species	70/846	223/8465	2.82e-19	8.29e-18	6.10e-18	70
hsa0541844	Breast	DCIS	Fluid shear stress and atherosclerosis	34/846	139/8465	5.31e-07	9.03e-06	6.65e-06	34
hsa0048041	Breast	DCIS	Glutathione metabolism	13/846	57/8465	3.44e-03	1.98e-02	1.46e-02	13
hsa0520853	Breast	DCIS	Chemical carcinogenesis - reactive oxygen species	70/846	223/8465	2.82e-19	8.29e-18	6.10e-18	70
hsa0541854	Breast	DCIS	Fluid shear stress and atherosclerosis	34/846	139/8465	5.31e-07	9.03e-06	6.65e-06	34
hsa0048051	Breast	DCIS	Glutathione metabolism	13/846	57/8465	3.44e-03	1.98e-02	1.46e-02	13
hsa0520820	Cervix	CC	Chemical carcinogenesis - reactive oxygen species	92/1267	223/8465	4.71e-22	5.09e-20	3.01e-20	92
hsa0541820	Cervix	CC	Fluid shear stress and atherosclerosis	50/1267	139/8465	5.71e-10	1.32e-08	7.81e-09	50

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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

MGST3

SNV

Missense_Mutation

novel

c.347N>G

p.Ala116Gly

p.A116G

O14880

protein_coding

tolerated(0.18)

benign(0.012)

TCGA-W8-A86G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

MGST3

SNV

Missense_Mutation

c.439G>A

p.Gly147Arg

p.G147R

O14880

protein_coding

deleterious_low_confidence(0.04)

benign(0.012)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MGST3

SNV

Missense_Mutation

rs764623433

c.251N>A

p.Arg84His

p.R84H

O14880

protein_coding

tolerated(0.08)

possibly_damaging(0.781)

TCGA-C5-A2LZ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Unknown

MGST3

SNV

Missense_Mutation

rs200730530

c.191N>T

p.Thr64Met

p.T64M

O14880

protein_coding

deleterious(0.03)

benign(0.393)

TCGA-VS-A9UJ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

MGST3

SNV

Missense_Mutation

rs769792197

c.361N>A

p.Ala121Thr

p.A121T

O14880

protein_coding

deleterious(0.01)

possibly_damaging(0.853)

TCGA-AX-A0J1-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

MGST3

SNV

Missense_Mutation

novel

c.364C>A

p.Leu122Ile

p.L122I

O14880

protein_coding

deleterious(0.04)

possibly_damaging(0.665)

TCGA-AX-A2HD-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Unknown

MGST3

SNV

Missense_Mutation

c.4N>A

p.Ala2Thr

p.A2T

O14880

protein_coding

tolerated(0.26)

benign(0.003)

TCGA-B5-A0JZ-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatin

MGST3

SNV

Missense_Mutation

novel

c.356N>A

p.Ser119Tyr

p.S119Y

O14880

protein_coding

tolerated(1)

benign(0.001)

TCGA-DF-A2KU-01

Endometrium

uterine corpus endometrioid carcinoma

Female

Unknown

I/II

Unknown

MGST3

SNV

Missense_Mutation

novel

c.54N>A

p.Ser18Arg

p.S18R

O14880

protein_coding

deleterious(0)

probably_damaging(0.985)

TCGA-EO-A22R-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

MGST3

SNV

Missense_Mutation

novel

c.219N>G

p.Phe73Leu

p.F73L

O14880

protein_coding

tolerated(0.09)

benign(0.102)

TCGA-ZP-A9CV-01

Liver

liver hepatocellular carcinoma

Male

<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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