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: PTPN12

Gene summary for PTPN12

Gene summary.

Gene information	Species	Human
	Gene symbol	PTPN12
	Gene ID	5782
	Gene name	protein tyrosine phosphatase non-receptor type 12
	Gene Alias	PTP-PEST
	Cytomap	7q11.23
	Gene Type	protein-coding
	GO ID	GO:0006464
	UniProtAcc	B4E105

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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
5782	PTPN12	CCI_1	Human	Cervix	CC	1.27e-02	7.87e-01	0.528
5782	PTPN12	CCI_2	Human	Cervix	CC	2.52e-14	1.48e+00	0.5249
5782	PTPN12	CCI_3	Human	Cervix	CC	5.39e-13	1.06e+00	0.516
5782	PTPN12	sample3	Human	Cervix	CC	2.34e-11	3.74e-01	0.1387
5782	PTPN12	T3	Human	Cervix	CC	8.75e-16	4.04e-01	0.1389
5782	PTPN12	HTA11_3410_2000001011	Human	Colorectum	AD	4.73e-10	-4.45e-01	0.0155
5782	PTPN12	HTA11_866_3004761011	Human	Colorectum	AD	8.25e-03	-3.54e-01	0.096
5782	PTPN12	HTA11_6801_2000001011	Human	Colorectum	SER	2.01e-02	-6.73e-01	0.0171
5782	PTPN12	HTA11_10711_2000001011	Human	Colorectum	AD	1.38e-02	-3.14e-01	0.0338
5782	PTPN12	HTA11_7696_3000711011	Human	Colorectum	AD	1.07e-05	-3.55e-01	0.0674
5782	PTPN12	HTA11_6818_2000001021	Human	Colorectum	AD	3.00e-03	-3.99e-01	0.0588
5782	PTPN12	A015-C-203	Human	Colorectum	FAP	3.46e-26	-3.72e-01	-0.1294
5782	PTPN12	A015-C-204	Human	Colorectum	FAP	1.19e-06	-2.62e-01	-0.0228
5782	PTPN12	A014-C-040	Human	Colorectum	FAP	1.98e-04	-3.39e-01	-0.1184
5782	PTPN12	A002-C-201	Human	Colorectum	FAP	2.52e-10	-2.18e-01	0.0324
5782	PTPN12	A001-C-119	Human	Colorectum	FAP	8.11e-07	2.88e-01	-0.1557
5782	PTPN12	A001-C-108	Human	Colorectum	FAP	2.14e-10	6.60e-02	-0.0272
5782	PTPN12	A002-C-205	Human	Colorectum	FAP	2.89e-20	-1.28e-01	-0.1236
5782	PTPN12	A015-C-005	Human	Colorectum	FAP	1.17e-02	-1.15e-01	-0.0336
5782	PTPN12	A015-C-006	Human	Colorectum	FAP	1.44e-13	-1.97e-01	-0.0994

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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
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
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:0071364	Colorectum	AD	cellular response to epidermal growth factor stimulus	21/3918	45/18723	9.94e-05	1.50e-03	21
GO:00708491	Colorectum	SER	response to epidermal growth factor	20/2897	49/18723	1.72e-05	5.15e-04	20
GO:00713641	Colorectum	SER	cellular response to epidermal growth factor stimulus	18/2897	45/18723	6.20e-05	1.44e-03	18
GO:00381271	Colorectum	SER	ERBB signaling pathway	35/2897	121/18723	1.21e-04	2.49e-03	35
GO:00071731	Colorectum	SER	epidermal growth factor receptor signaling pathway	32/2897	108/18723	1.42e-04	2.82e-03	32
GO:00064701	Colorectum	SER	protein dephosphorylation	65/2897	281/18723	4.44e-04	6.51e-03	65
GO:19011851	Colorectum	SER	negative regulation of ERBB signaling pathway	12/2897	32/18723	2.00e-03	1.98e-02	12
GO:00163111	Colorectum	SER	dephosphorylation	86/2897	417/18723	2.73e-03	2.46e-02	86
GO:00071734	Colorectum	FAP	epidermal growth factor receptor signaling pathway	42/2622	108/18723	1.29e-10	3.77e-08	42
GO:00381274	Colorectum	FAP	ERBB signaling pathway	45/2622	121/18723	1.64e-10	4.38e-08	45
GO:00163113	Colorectum	FAP	dephosphorylation	95/2622	417/18723	7.07e-07	3.32e-05	95
GO:00064704	Colorectum	FAP	protein dephosphorylation	69/2622	281/18723	1.47e-06	6.39e-05	69
GO:19011842	Colorectum	FAP	regulation of ERBB signaling pathway	27/2622	79/18723	4.77e-06	1.57e-04	27
GO:19011853	Colorectum	FAP	negative regulation of ERBB signaling pathway	15/2622	32/18723	8.00e-06	2.38e-04	15
GO:00420582	Colorectum	FAP	regulation of epidermal growth factor receptor signaling pathway	25/2622	73/18723	1.02e-05	2.93e-04	25
GO:00708493	Colorectum	FAP	response to epidermal growth factor	17/2622	49/18723	2.17e-04	3.09e-03	17
GO:00713643	Colorectum	FAP	cellular response to epidermal growth factor stimulus	16/2622	45/18723	2.39e-04	3.34e-03	16
GO:0048008	Colorectum	FAP	platelet-derived growth factor receptor signaling pathway	16/2622	56/18723	3.40e-03	2.47e-02	16
GO:0035335	Colorectum	FAP	peptidyl-tyrosine dephosphorylation	23/2622	97/18723	6.95e-03	4.26e-02	23
GO:00071735	Colorectum	CRC	epidermal growth factor receptor signaling pathway	39/2078	108/18723	6.90e-12	5.90e-09	39

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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

PTPN12

SNV

Missense_Mutation

c.824N>G

p.Ser275Cys

p.S275C

Q05209

protein_coding

deleterious(0.02)

probably_damaging(1)

TCGA-A1-A0SI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PTPN12

SNV

Missense_Mutation

c.263A>T

p.Tyr88Phe

p.Y88F

Q05209

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-A8-A07U-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

PTPN12

SNV

Missense_Mutation

c.824N>T

p.Ser275Phe

p.S275F

Q05209

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PTPN12

SNV

Missense_Mutation

rs766786152

c.1427N>G

p.Ser476Cys

p.S476C

Q05209

protein_coding

tolerated_low_confidence(0.08)

probably_damaging(0.91)

TCGA-BH-A0DK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

PTPN12

SNV

Missense_Mutation

c.2063C>T

p.Ala688Val

p.A688V

Q05209

protein_coding

deleterious(0)

benign(0.368)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

PTPN12

SNV

Missense_Mutation

c.171N>C

p.Glu57Asp

p.E57D

Q05209

protein_coding

deleterious(0.04)

benign(0.375)

TCGA-BH-A18T-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PTPN12

insertion

Frame_Shift_Ins

novel

c.1281_1282insA

p.Leu430IlefsTer8

p.L430Ifs*8

Q05209

protein_coding

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PTPN12

insertion

In_Frame_Ins

novel

c.1187_1188insCCAATTCTTTCTGTTTTA

p.Val396_Ser397insGlnPhePheLeuPheTyr

p.V396_S397insQFFLFY

Q05209

protein_coding

TCGA-AN-A0FS-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PTPN12

SNV

Missense_Mutation

c.824C>T

p.Ser275Phe

p.S275F

Q05209

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-C5-A7X5-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

carboplatin

PTPN12

SNV

Missense_Mutation

c.772G>C

p.Glu258Gln

p.E258Q

Q05209

protein_coding

deleterious(0.02)

probably_damaging(0.974)

TCGA-EK-A2PI-01

Cervix

cervical & endocervical cancer

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
5782	PTPN12	PROTEIN PHOSPHATASE, DRUGGABLE GENOME, KINASE		CRIZOTINIB	CRIZOTINIB	29578538
5782	PTPN12	PROTEIN PHOSPHATASE, DRUGGABLE GENOME, KINASE		SUNITINIB	SUNITINIB	29578538
5782	PTPN12	PROTEIN PHOSPHATASE, DRUGGABLE GENOME, KINASE		GNF-PF-231	CHEMBL601167

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