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: GPX7

Gene summary for GPX7

Gene summary.

Gene information	Species	Human
	Gene symbol	GPX7
	Gene ID	2882
	Gene name	glutathione peroxidase 7
	Gene Alias	CL683
	Cytomap	1p32.3
	Gene Type	protein-coding
	GO ID	GO:0006950
	UniProtAcc	Q96SL4

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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
2882	GPX7	LZE7T	Human	Esophagus	ESCC	8.65e-05	2.53e-01	0.0667
2882	GPX7	LZE8T	Human	Esophagus	ESCC	5.39e-05	1.92e-01	0.067
2882	GPX7	LZE24T	Human	Esophagus	ESCC	4.70e-13	3.05e-01	0.0596
2882	GPX7	LZE6T	Human	Esophagus	ESCC	1.59e-10	5.11e-01	0.0845
2882	GPX7	P2T-E	Human	Esophagus	ESCC	2.31e-32	5.99e-01	0.1177
2882	GPX7	P4T-E	Human	Esophagus	ESCC	8.18e-35	7.55e-01	0.1323
2882	GPX7	P5T-E	Human	Esophagus	ESCC	8.57e-07	2.42e-01	0.1327
2882	GPX7	P8T-E	Human	Esophagus	ESCC	1.97e-39	6.98e-01	0.0889
2882	GPX7	P9T-E	Human	Esophagus	ESCC	2.43e-10	2.72e-01	0.1131
2882	GPX7	P10T-E	Human	Esophagus	ESCC	2.97e-49	9.73e-01	0.116
2882	GPX7	P12T-E	Human	Esophagus	ESCC	4.82e-43	8.04e-01	0.1122
2882	GPX7	P15T-E	Human	Esophagus	ESCC	2.53e-14	3.55e-01	0.1149
2882	GPX7	P16T-E	Human	Esophagus	ESCC	1.27e-44	9.50e-01	0.1153
2882	GPX7	P19T-E	Human	Esophagus	ESCC	1.22e-02	3.14e-01	0.1662
2882	GPX7	P20T-E	Human	Esophagus	ESCC	3.08e-21	4.78e-01	0.1124
2882	GPX7	P21T-E	Human	Esophagus	ESCC	8.21e-19	3.97e-01	0.1617
2882	GPX7	P24T-E	Human	Esophagus	ESCC	3.91e-09	2.15e-01	0.1287
2882	GPX7	P26T-E	Human	Esophagus	ESCC	3.83e-08	2.15e-01	0.1276
2882	GPX7	P27T-E	Human	Esophagus	ESCC	4.03e-19	3.67e-01	0.1055
2882	GPX7	P28T-E	Human	Esophagus	ESCC	1.38e-29	5.46e-01	0.1149

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:0006979111	Esophagus	ESCC	response to oxidative stress	303/8552	446/18723	7.15e-22	1.30e-19	303
GO:0062197111	Esophagus	ESCC	cellular response to chemical stress	234/8552	337/18723	5.37e-19	5.97e-17	234
GO:0034599111	Esophagus	ESCC	cellular response to oxidative stress	197/8552	288/18723	3.76e-15	2.15e-13	197
GO:000963620	Esophagus	ESCC	response to toxic substance	150/8552	262/18723	1.00e-04	7.12e-04	150
GO:1990748110	Esophagus	ESCC	cellular detoxification	70/8552	116/18723	1.02e-03	5.17e-03	70
GO:0097237110	Esophagus	ESCC	cellular response to toxic substance	72/8552	124/18723	3.65e-03	1.49e-02	72
GO:0098869110	Esophagus	ESCC	cellular oxidant detoxification	60/8552	101/18723	3.76e-03	1.53e-02	60
GO:000697912	Liver	Cirrhotic	response to oxidative stress	196/4634	446/18723	2.80e-19	5.86e-17	196
GO:006219712	Liver	Cirrhotic	cellular response to chemical stress	147/4634	337/18723	1.84e-14	1.72e-12	147
GO:003459912	Liver	Cirrhotic	cellular response to oxidative stress	127/4634	288/18723	4.29e-13	3.32e-11	127
GO:000963612	Liver	Cirrhotic	response to toxic substance	104/4634	262/18723	5.63e-08	1.74e-06	104
GO:00987547	Liver	Cirrhotic	detoxification	60/4634	152/18723	4.09e-05	4.86e-04	60
GO:00972377	Liver	Cirrhotic	cellular response to toxic substance	50/4634	124/18723	9.20e-05	9.79e-04	50
GO:19907487	Liver	Cirrhotic	cellular detoxification	47/4634	116/18723	1.28e-04	1.26e-03	47
GO:00988697	Liver	Cirrhotic	cellular oxidant detoxification	38/4634	101/18723	2.72e-03	1.59e-02	38
GO:000697922	Liver	HCC	response to oxidative stress	281/7958	446/18723	9.75e-19	1.24e-16	281
GO:006219722	Liver	HCC	cellular response to chemical stress	216/7958	337/18723	6.86e-16	5.44e-14	216
GO:003459922	Liver	HCC	cellular response to oxidative stress	183/7958	288/18723	3.65e-13	1.93e-11	183
GO:000963622	Liver	HCC	response to toxic substance	153/7958	262/18723	1.37e-07	2.58e-06	153
GO:199074812	Liver	HCC	cellular detoxification	70/7958	116/18723	7.87e-05	7.02e-04	70

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05014210	Esophagus	ESCC	Amyotrophic lateral sclerosis	266/4205	364/8465	1.31e-20	2.20e-18	1.13e-18	266
hsa05016210	Esophagus	ESCC	Huntington disease	226/4205	306/8465	1.38e-18	8.72e-17	4.46e-17	226
hsa05022210	Esophagus	ESCC	Pathways of neurodegeneration - multiple diseases	318/4205	476/8465	6.10e-15	2.04e-13	1.05e-13	318
hsa0048018	Esophagus	ESCC	Glutathione metabolism	44/4205	57/8465	1.81e-05	9.03e-05	4.63e-05	44
hsa0501438	Esophagus	ESCC	Amyotrophic lateral sclerosis	266/4205	364/8465	1.31e-20	2.20e-18	1.13e-18	266
hsa0501638	Esophagus	ESCC	Huntington disease	226/4205	306/8465	1.38e-18	8.72e-17	4.46e-17	226
hsa0502238	Esophagus	ESCC	Pathways of neurodegeneration - multiple diseases	318/4205	476/8465	6.10e-15	2.04e-13	1.05e-13	318
hsa0048019	Esophagus	ESCC	Glutathione metabolism	44/4205	57/8465	1.81e-05	9.03e-05	4.63e-05	44
hsa0501614	Liver	Cirrhotic	Huntington disease	172/2530	306/8465	1.65e-22	1.10e-20	6.77e-21	172
hsa0501414	Liver	Cirrhotic	Amyotrophic lateral sclerosis	187/2530	364/8465	1.56e-18	6.50e-17	4.01e-17	187
hsa0502214	Liver	Cirrhotic	Pathways of neurodegeneration - multiple diseases	217/2530	476/8465	7.30e-14	2.03e-12	1.25e-12	217
hsa004809	Liver	Cirrhotic	Glutathione metabolism	30/2530	57/8465	2.63e-04	1.72e-03	1.06e-03	30
hsa0501615	Liver	Cirrhotic	Huntington disease	172/2530	306/8465	1.65e-22	1.10e-20	6.77e-21	172
hsa0501415	Liver	Cirrhotic	Amyotrophic lateral sclerosis	187/2530	364/8465	1.56e-18	6.50e-17	4.01e-17	187
hsa0502215	Liver	Cirrhotic	Pathways of neurodegeneration - multiple diseases	217/2530	476/8465	7.30e-14	2.03e-12	1.25e-12	217
hsa0048012	Liver	Cirrhotic	Glutathione metabolism	30/2530	57/8465	2.63e-04	1.72e-03	1.06e-03	30
hsa0501622	Liver	HCC	Huntington disease	219/4020	306/8465	3.06e-18	3.42e-16	1.90e-16	219
hsa0501422	Liver	HCC	Amyotrophic lateral sclerosis	252/4020	364/8465	8.85e-18	7.41e-16	4.12e-16	252
hsa0502222	Liver	HCC	Pathways of neurodegeneration - multiple diseases	298/4020	476/8465	6.59e-12	1.30e-10	7.22e-11	298
hsa0048022	Liver	HCC	Glutathione metabolism	42/4020	57/8465	5.00e-05	2.62e-04	1.46e-04	42

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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

GPX7

SNV

Missense_Mutation

novel

c.434G>T

p.Trp145Leu

p.W145L

Q96SL4

protein_coding

deleterious(0)

possibly_damaging(0.9)

TCGA-A2-A25A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Cytoxan

GPX7

SNV

Missense_Mutation

novel

c.247N>A

p.Ala83Thr

p.A83T

Q96SL4

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-AC-A62V-01

Breast

breast invasive carcinoma

Male

<65

III/IV

Targeted Molecular therapy

denosumab

GPX7

insertion

Frame_Shift_Ins

novel

c.299_300insGGTGTTTGCTAACATGTTTGTATCGTGGTGCATGTGCATACCTA

p.Ile100MetfsTer64

p.I100Mfs*64

Q96SL4

protein_coding

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

GPX7

SNV

Missense_Mutation

novel

c.467N>C

p.Val156Ala

p.V156A

Q96SL4

protein_coding

deleterious(0.03)

benign(0.296)

TCGA-CA-6717-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Chemotherapy

oxaliplatin

GPX7

SNV

Missense_Mutation

c.56C>T

p.Ala19Val

p.A19V

Q96SL4

protein_coding

tolerated(0.28)

benign(0)

TCGA-CK-5913-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

GPX7

SNV

Missense_Mutation

novel

c.75C>A

p.Phe25Leu

p.F25L

Q96SL4

protein_coding

tolerated(0.11)

benign(0.325)

TCGA-F5-6814-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

GPX7

SNV

Missense_Mutation

novel

c.128A>C

p.Tyr43Ser

p.Y43S

Q96SL4

protein_coding

tolerated(0.05)

probably_damaging(0.996)

TCGA-AJ-A23O-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

GPX7

SNV

Missense_Mutation

novel

c.520N>T

p.Ala174Ser

p.A174S

Q96SL4

protein_coding

tolerated(0.49)

benign(0.001)

TCGA-AP-A1DK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

GPX7

SNV

Missense_Mutation

novel

c.368C>A

p.Thr123Asn

p.T123N

Q96SL4

protein_coding

tolerated(0.1)

benign(0.005)

TCGA-AX-A2HD-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Unknown

GPX7

SNV

Missense_Mutation

novel

c.388A>G

p.Lys130Glu

p.K130E

Q96SL4

protein_coding

deleterious(0.04)

benign(0.181)

TCGA-B5-A1MX-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Hormone Therapy

megace

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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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