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: PRDX3

Gene summary for PRDX3

Gene summary.

Gene information	Species	Human
	Gene symbol	PRDX3
	Gene ID	10935
	Gene name	peroxiredoxin 3
	Gene Alias	AOP-1
	Cytomap	10q26.11
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	P30048

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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
10935	PRDX3	HTA11_1938_2000001011	Human	Colorectum	AD	6.49e-09	6.01e-01	-0.0811
10935	PRDX3	HTA11_78_2000001011	Human	Colorectum	AD	1.02e-05	3.19e-01	-0.1088
10935	PRDX3	HTA11_347_2000001011	Human	Colorectum	AD	1.02e-10	3.72e-01	-0.1954
10935	PRDX3	HTA11_696_2000001011	Human	Colorectum	AD	1.41e-02	1.70e-01	-0.1464
10935	PRDX3	HTA11_1391_2000001011	Human	Colorectum	AD	2.21e-03	3.28e-01	-0.059
10935	PRDX3	HTA11_7862_2000001011	Human	Colorectum	AD	1.55e-04	4.17e-01	-0.0179
10935	PRDX3	HTA11_866_3004761011	Human	Colorectum	AD	7.05e-08	3.83e-01	0.096
10935	PRDX3	HTA11_4255_2000001011	Human	Colorectum	SER	6.14e-06	5.64e-01	0.0446
10935	PRDX3	HTA11_8622_2000001021	Human	Colorectum	SER	4.38e-02	3.56e-01	0.0528
10935	PRDX3	HTA11_6801_2000001011	Human	Colorectum	SER	4.51e-12	9.89e-01	0.0171
10935	PRDX3	HTA11_7696_3000711011	Human	Colorectum	AD	2.75e-08	2.53e-01	0.0674
10935	PRDX3	HTA11_7469_2000001011	Human	Colorectum	AD	3.77e-04	6.06e-01	-0.0124
10935	PRDX3	HTA11_6818_2000001021	Human	Colorectum	AD	3.33e-05	3.00e-01	0.0588
10935	PRDX3	HTA11_99999970781_79442	Human	Colorectum	MSS	8.78e-29	6.97e-01	0.294
10935	PRDX3	HTA11_99999965062_69753	Human	Colorectum	MSI-H	1.16e-05	1.04e+00	0.3487
10935	PRDX3	HTA11_99999965104_69814	Human	Colorectum	MSS	3.99e-12	5.90e-01	0.281
10935	PRDX3	HTA11_99999971662_82457	Human	Colorectum	MSS	1.17e-17	5.71e-01	0.3859
10935	PRDX3	HTA11_99999974143_84620	Human	Colorectum	MSS	2.03e-03	2.35e-01	0.3005
10935	PRDX3	AEH-subject1	Human	Endometrium	AEH	4.90e-06	-2.75e-01	-0.3059
10935	PRDX3	AEH-subject2	Human	Endometrium	AEH	1.50e-08	-2.73e-01	-0.2525

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:0006979	Colorectum	AD	response to oxidative stress	145/3918	446/18723	5.16e-09	3.23e-07	145
GO:0062197	Colorectum	AD	cellular response to chemical stress	109/3918	337/18723	5.33e-07	1.95e-05	109
GO:0000302	Colorectum	AD	response to reactive oxygen species	78/3918	222/18723	6.17e-07	2.21e-05	78
GO:0009636	Colorectum	AD	response to toxic substance	88/3918	262/18723	1.12e-06	3.72e-05	88
GO:0030099	Colorectum	AD	myeloid cell differentiation	119/3918	381/18723	1.24e-06	4.01e-05	119
GO:0034599	Colorectum	AD	cellular response to oxidative stress	94/3918	288/18723	2.03e-06	6.02e-05	94
GO:0043281	Colorectum	AD	regulation of cysteine-type endopeptidase activity involved in apoptotic process	72/3918	209/18723	3.70e-06	1.03e-04	72
GO:2000116	Colorectum	AD	regulation of cysteine-type endopeptidase activity	79/3918	235/18723	3.74e-06	1.03e-04	79
GO:0052547	Colorectum	AD	regulation of peptidase activity	137/3918	461/18723	4.12e-06	1.12e-04	137
GO:0010563	Colorectum	AD	negative regulation of phosphorus metabolic process	130/3918	442/18723	1.26e-05	2.76e-04	130
GO:0045936	Colorectum	AD	negative regulation of phosphate metabolic process	129/3918	441/18723	1.81e-05	3.76e-04	129
GO:0051348	Colorectum	AD	negative regulation of transferase activity	85/3918	268/18723	2.07e-05	4.19e-04	85
GO:0045861	Colorectum	AD	negative regulation of proteolysis	106/3918	351/18723	2.33e-05	4.57e-04	106
GO:0042542	Colorectum	AD	response to hydrogen peroxide	52/3918	146/18723	2.83e-05	5.30e-04	52
GO:0001890	Colorectum	AD	placenta development	51/3918	144/18723	3.99e-05	7.16e-04	51
GO:0098754	Colorectum	AD	detoxification	53/3918	152/18723	4.63e-05	7.98e-04	53
GO:0052548	Colorectum	AD	regulation of endopeptidase activity	124/3918	432/18723	6.58e-05	1.07e-03	124
GO:0042326	Colorectum	AD	negative regulation of phosphorylation	112/3918	385/18723	8.02e-05	1.27e-03	112
GO:0097237	Colorectum	AD	cellular response to toxic substance	44/3918	124/18723	1.24e-04	1.80e-03	44
GO:1990748	Colorectum	AD	cellular detoxification	41/3918	116/18723	2.29e-04	2.97e-03	41

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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

PRDX3

SNV

Missense_Mutation

rs548327727

c.604N>A

p.Asp202Asn

p.D202N

P30048

protein_coding

deleterious(0.03)

probably_damaging(0.994)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PRDX3

SNV

Missense_Mutation

c.301N>T

p.Pro101Ser

p.P101S

P30048

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-CK-4951-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

PRDX3

SNV

Missense_Mutation

rs548327727

c.604G>A

p.Asp202Asn

p.D202N

P30048

protein_coding

deleterious(0.03)

probably_damaging(0.994)

TCGA-AX-A2HC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

PRDX3

SNV

Missense_Mutation

rs751585321

c.640C>T

p.Arg214Cys

p.R214C

P30048

protein_coding

deleterious(0.04)

benign(0.074)

TCGA-B5-A0JZ-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatin

PRDX3

SNV

Missense_Mutation

rs779344159

c.361G>A

p.Glu121Lys

p.E121K

P30048

protein_coding

tolerated(0.11)

possibly_damaging(0.79)

TCGA-BS-A0UF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

PRDX3

SNV

Missense_Mutation

novel

c.223N>G

p.Thr75Ala

p.T75A

P30048

protein_coding

deleterious(0.02)

possibly_damaging(0.878)

TCGA-D1-A1NY-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Chemotherapy

carboplatin

PRDX3

SNV

Missense_Mutation

novel

c.443G>T

p.Arg148Ile

p.R148I

P30048

protein_coding

deleterious(0)

possibly_damaging(0.859)

TCGA-E6-A1LX-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

PRDX3

SNV

Missense_Mutation

novel

c.221N>A

p.Gly74Asp

p.G74D

P30048

protein_coding

deleterious(0.03)

probably_damaging(0.993)

TCGA-E6-A2P9-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

PRDX3

SNV

Missense_Mutation

rs772428160

c.128N>C

p.Leu43Ser

p.L43S

P30048

protein_coding

tolerated(0.21)

benign(0.013)

TCGA-EO-A3AY-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

PRDX3

SNV

Missense_Mutation

novel

c.541C>A

p.Leu181Ile

p.L181I

P30048

protein_coding

tolerated(1)

benign(0.005)

TCGA-FI-A2D5-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatinum

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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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