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: GSTO1

Gene summary for GSTO1

Gene summary.

Gene information	Species	Human
	Gene symbol	GSTO1
	Gene ID	9446
	Gene name	glutathione S-transferase omega 1
	Gene Alias	GSTO 1-1
	Cytomap	10q25.1
	Gene Type	protein-coding
	GO ID	GO:0003008
	UniProtAcc	P78417

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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
9446	GSTO1	CA_HPV_1	Human	Cervix	CC	3.47e-12	4.30e-02	0.0264
9446	GSTO1	CCI_1	Human	Cervix	CC	6.84e-05	-5.81e-01	0.528
9446	GSTO1	CCI_3	Human	Cervix	CC	4.06e-05	-5.35e-01	0.516
9446	GSTO1	CCII_1	Human	Cervix	CC	8.46e-22	-6.99e-01	0.3249
9446	GSTO1	H2	Human	Cervix	HSIL_HPV	4.18e-07	-3.99e-01	0.0632
9446	GSTO1	L1	Human	Cervix	CC	2.92e-10	-4.96e-01	0.0802
9446	GSTO1	HTA11_3410_2000001011	Human	Colorectum	AD	6.94e-04	2.22e-01	0.0155
9446	GSTO1	HTA11_2487_2000001011	Human	Colorectum	SER	3.95e-10	5.92e-01	-0.1808
9446	GSTO1	HTA11_1938_2000001011	Human	Colorectum	AD	3.66e-17	7.02e-01	-0.0811
9446	GSTO1	HTA11_78_2000001011	Human	Colorectum	AD	1.16e-02	2.77e-01	-0.1088
9446	GSTO1	HTA11_347_2000001011	Human	Colorectum	AD	8.22e-15	4.71e-01	-0.1954
9446	GSTO1	HTA11_411_2000001011	Human	Colorectum	SER	1.66e-05	7.12e-01	-0.2602
9446	GSTO1	HTA11_3361_2000001011	Human	Colorectum	AD	2.87e-04	3.66e-01	-0.1207
9446	GSTO1	HTA11_83_2000001011	Human	Colorectum	SER	2.34e-05	5.13e-01	-0.1526
9446	GSTO1	HTA11_696_2000001011	Human	Colorectum	AD	5.17e-15	4.89e-01	-0.1464
9446	GSTO1	HTA11_866_2000001011	Human	Colorectum	AD	7.58e-05	2.87e-01	-0.1001
9446	GSTO1	HTA11_1391_2000001011	Human	Colorectum	AD	4.61e-22	7.67e-01	-0.059
9446	GSTO1	HTA11_2992_2000001011	Human	Colorectum	SER	5.61e-08	7.37e-01	-0.1706
9446	GSTO1	HTA11_5212_2000001011	Human	Colorectum	AD	6.51e-03	4.35e-01	-0.2061
9446	GSTO1	HTA11_546_2000001011	Human	Colorectum	AD	1.91e-06	4.93e-01	-0.0842

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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
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:1990748112	Thyroid	PTC	cellular detoxification	56/5968	116/18723	1.63e-04	1.26e-03	56
GO:0097237112	Thyroid	PTC	cellular response to toxic substance	59/5968	124/18723	1.83e-04	1.39e-03	59
GO:0098869111	Thyroid	PTC	cellular oxidant detoxification	49/5968	101/18723	3.52e-04	2.41e-03	49
GO:00510518	Thyroid	PTC	negative regulation of transport	176/5968	470/18723	5.44e-03	2.49e-02	176
GO:0098754110	Thyroid	PTC	detoxification	63/5968	152/18723	7.92e-03	3.34e-02	63
GO:0009410111	Thyroid	PTC	response to xenobiotic stimulus	171/5968	462/18723	1.00e-02	4.07e-02	171
GO:005123532	Thyroid	ATC	maintenance of location	152/6293	327/18723	7.84e-07	1.04e-05	152
GO:005165133	Thyroid	ATC	maintenance of location in cell	105/6293	214/18723	1.92e-06	2.31e-05	105
GO:004668523	Thyroid	ATC	response to arsenic-containing substance	24/6293	33/18723	4.98e-06	5.40e-05	24
GO:000599615	Thyroid	ATC	monosaccharide metabolic process	118/6293	257/18723	2.56e-05	2.20e-04	118
GO:007124323	Thyroid	ATC	cellular response to arsenic-containing substance	16/6293	20/18723	2.79e-05	2.36e-04	16
GO:000963634	Thyroid	ATC	response to toxic substance	119/6293	262/18723	4.30e-05	3.48e-04	119
GO:199074833	Thyroid	ATC	cellular detoxification	58/6293	116/18723	1.88e-04	1.26e-03	58
GO:009723733	Thyroid	ATC	cellular response to toxic substance	61/6293	124/18723	2.31e-04	1.49e-03	61
GO:009886932	Thyroid	ATC	cellular oxidant detoxification	51/6293	101/18723	3.29e-04	2.05e-03	51
GO:000657522	Thyroid	ATC	cellular modified amino acid metabolic process	82/6293	188/18723	2.60e-03	1.20e-02	82
GO:000941027	Thyroid	ATC	response to xenobiotic stimulus	184/6293	462/18723	2.70e-03	1.23e-02	184
GO:009875433	Thyroid	ATC	detoxification	66/6293	152/18723	7.23e-03	2.85e-02	66
GO:005105114	Thyroid	ATC	negative regulation of transport	183/6293	470/18723	8.12e-03	3.13e-02	183

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
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
hsa0522510	Cervix	CC	Hepatocellular carcinoma	40/1267	168/8465	1.52e-03	6.39e-03	3.78e-03	40
hsa05208110	Cervix	CC	Chemical carcinogenesis - reactive oxygen species	92/1267	223/8465	4.71e-22	5.09e-20	3.01e-20	92
hsa05418110	Cervix	CC	Fluid shear stress and atherosclerosis	50/1267	139/8465	5.71e-10	1.32e-08	7.81e-09	50
hsa0522513	Cervix	CC	Hepatocellular carcinoma	40/1267	168/8465	1.52e-03	6.39e-03	3.78e-03	40
hsa0520825	Cervix	HSIL_HPV	Chemical carcinogenesis - reactive oxygen species	30/459	223/8465	3.28e-06	5.65e-05	4.57e-05	30
hsa0541825	Cervix	HSIL_HPV	Fluid shear stress and atherosclerosis	16/459	139/8465	3.41e-03	2.08e-02	1.68e-02	16
hsa0520835	Cervix	HSIL_HPV	Chemical carcinogenesis - reactive oxygen species	30/459	223/8465	3.28e-06	5.65e-05	4.57e-05	30
hsa0541835	Cervix	HSIL_HPV	Fluid shear stress and atherosclerosis	16/459	139/8465	3.41e-03	2.08e-02	1.68e-02	16
hsa05208	Colorectum	AD	Chemical carcinogenesis - reactive oxygen species	126/2092	223/8465	1.01e-24	1.68e-22	1.07e-22	126
hsa05418	Colorectum	AD	Fluid shear stress and atherosclerosis	54/2092	139/8465	1.41e-04	1.16e-03	7.37e-04	54
hsa05225	Colorectum	AD	Hepatocellular carcinoma	59/2092	168/8465	1.50e-03	8.69e-03	5.54e-03	59
hsa00480	Colorectum	AD	Glutathione metabolism	23/2092	57/8465	6.52e-03	2.76e-02	1.76e-02	23
hsa052081	Colorectum	AD	Chemical carcinogenesis - reactive oxygen species	126/2092	223/8465	1.01e-24	1.68e-22	1.07e-22	126
hsa054181	Colorectum	AD	Fluid shear stress and atherosclerosis	54/2092	139/8465	1.41e-04	1.16e-03	7.37e-04	54
hsa052251	Colorectum	AD	Hepatocellular carcinoma	59/2092	168/8465	1.50e-03	8.69e-03	5.54e-03	59
hsa004801	Colorectum	AD	Glutathione metabolism	23/2092	57/8465	6.52e-03	2.76e-02	1.76e-02	23
hsa052082	Colorectum	SER	Chemical carcinogenesis - reactive oxygen species	103/1580	223/8465	1.60e-21	7.57e-20	5.50e-20	103
hsa054182	Colorectum	SER	Fluid shear stress and atherosclerosis	40/1580	139/8465	2.28e-03	1.75e-02	1.27e-02	40

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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

GSTO1

SNV

Missense_Mutation

c.641N>T

p.Ala214Val

p.A214V

P78417

protein_coding

deleterious(0.02)

possibly_damaging(0.551)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

GSTO1

insertion

Frame_Shift_Ins

novel

c.385_386insTCCCAGCACTTTGGGAGGCTGAGGCAGATGGATCACCTGAG

p.Ser129IlefsTer28

p.S129Ifs*28

P78417

protein_coding

TCGA-BH-A0EE-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

docetaxel

GSTO1

SNV

Missense_Mutation

novel

c.311C>A

p.Pro104Gln

p.P104Q

P78417

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

GSTO1

SNV

Missense_Mutation

c.43N>A

p.Pro15Thr

p.P15T

P78417

protein_coding

tolerated(0.06)

benign(0.034)

TCGA-IR-A3LL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

GSTO1

SNV

Missense_Mutation

rs754091728

c.253N>A

p.Glu85Lys

p.E85K

P78417

protein_coding

deleterious(0)

probably_damaging(0.971)

TCGA-AX-A0J0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

GSTO1

SNV

Missense_Mutation

novel

c.182N>G

p.Glu61Gly

p.E61G

P78417

protein_coding

deleterious(0)

possibly_damaging(0.795)

TCGA-AX-A0J1-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

GSTO1

SNV

Missense_Mutation

novel

c.602N>C

p.Leu201Pro

p.L201P

P78417

protein_coding

tolerated(0.23)

possibly_damaging(0.896)

TCGA-AX-A2HJ-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

GSTO1

SNV

Missense_Mutation

novel

c.161N>C

p.Ile54Thr

p.I54T

P78417

protein_coding

deleterious(0.01)

possibly_damaging(0.573)

TCGA-B5-A3FA-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

GSTO1

SNV

Missense_Mutation

c.470N>C

p.Leu157Pro

p.L157P

P78417

protein_coding

deleterious(0)

probably_damaging(0.938)

TCGA-BS-A0UA-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

GSTO1

SNV

Missense_Mutation

c.170N>C

p.Lys57Thr

p.K57T

P78417

protein_coding

deleterious(0)

possibly_damaging(0.894)

TCGA-D1-A17Q-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<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
9446	GSTO1	ENZYME, DRUGGABLE GENOME	inhibitor	405067312
9446	GSTO1	ENZYME, DRUGGABLE GENOME		ARSENIC TRIOXIDE		15761769
9446	GSTO1	ENZYME, DRUGGABLE GENOME	inhibitor	405067313

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