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: PTPRK

Gene summary for PTPRK

Gene summary.

Gene information	Species	Human
	Gene symbol	PTPRK
	Gene ID	5796
	Gene name	protein tyrosine phosphatase receptor type K
	Gene Alias	R-PTP-kappa
	Cytomap	6q22.33
	Gene Type	protein-coding
	GO ID	GO:0000302
	UniProtAcc	Q15262

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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
5796	PTPRK	P76T-E	Human	Esophagus	ESCC	2.44e-45	9.74e-01	0.1207
5796	PTPRK	P79T-E	Human	Esophagus	ESCC	3.66e-39	7.21e-01	0.1154
5796	PTPRK	P80T-E	Human	Esophagus	ESCC	5.15e-42	1.48e+00	0.155
5796	PTPRK	P82T-E	Human	Esophagus	ESCC	3.91e-18	1.48e+00	0.1072
5796	PTPRK	P83T-E	Human	Esophagus	ESCC	6.45e-47	1.59e+00	0.1738
5796	PTPRK	P84T-E	Human	Esophagus	ESCC	1.26e-27	1.37e+00	0.0933
5796	PTPRK	P89T-E	Human	Esophagus	ESCC	3.02e-19	2.32e+00	0.1752
5796	PTPRK	P91T-E	Human	Esophagus	ESCC	6.57e-12	1.68e+00	0.1828
5796	PTPRK	P104T-E	Human	Esophagus	ESCC	5.81e-10	7.70e-01	0.0931
5796	PTPRK	P107T-E	Human	Esophagus	ESCC	4.61e-54	1.83e+00	0.171
5796	PTPRK	P126T-E	Human	Esophagus	ESCC	5.70e-06	1.19e+00	0.1125
5796	PTPRK	P127T-E	Human	Esophagus	ESCC	2.51e-15	4.67e-01	0.0826
5796	PTPRK	P128T-E	Human	Esophagus	ESCC	5.20e-53	2.07e+00	0.1241
5796	PTPRK	P130T-E	Human	Esophagus	ESCC	1.28e-60	1.43e+00	0.1676
5796	PTPRK	NAFLD1	Human	Liver	NAFLD	5.00e-10	1.15e+00	-0.04
5796	PTPRK	S43	Human	Liver	Cirrhotic	1.31e-09	-9.90e-02	-0.0187
5796	PTPRK	HCC1_Meng	Human	Liver	HCC	1.61e-59	-4.72e-01	0.0246
5796	PTPRK	HCC2_Meng	Human	Liver	HCC	4.32e-56	-1.24e-02	0.0107
5796	PTPRK	cirrhotic1	Human	Liver	Cirrhotic	6.98e-11	-5.05e-02	0.0202
5796	PTPRK	cirrhotic2	Human	Liver	Cirrhotic	1.47e-10	-2.04e-01	0.0201

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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
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
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:00315898	Cervix	CC	cell-substrate adhesion	96/2311	363/18723	1.48e-13	8.85e-11	96
GO:000697910	Cervix	CC	response to oxidative stress	102/2311	446/18723	2.99e-10	4.36e-08	102
GO:01501159	Cervix	CC	cell-substrate junction organization	37/2311	101/18723	3.20e-10	4.46e-08	37
GO:00421108	Cervix	CC	T cell activation	107/2311	487/18723	1.24e-09	1.46e-07	107
GO:00506737	Cervix	CC	epithelial cell proliferation	98/2311	437/18723	2.01e-09	2.15e-07	98
GO:00070448	Cervix	CC	cell-substrate junction assembly	34/2311	95/18723	3.35e-09	3.45e-07	34
GO:00071608	Cervix	CC	cell-matrix adhesion	60/2311	233/18723	1.58e-08	1.23e-06	60
GO:000030210	Cervix	CC	response to reactive oxygen species	56/2311	222/18723	1.00e-07	5.25e-06	56
GO:006219710	Cervix	CC	cellular response to chemical stress	76/2311	337/18723	1.01e-07	5.25e-06	76
GO:00506787	Cervix	CC	regulation of epithelial cell proliferation	83/2311	381/18723	1.31e-07	6.42e-06	83
GO:00343298	Cervix	CC	cell junction assembly	88/2311	420/18723	3.42e-07	1.38e-05	88
GO:00480417	Cervix	CC	focal adhesion assembly	28/2311	87/18723	9.86e-07	3.45e-05	28
GO:003459910	Cervix	CC	cellular response to oxidative stress	63/2311	288/18723	3.58e-06	9.50e-05	63
GO:00712148	Cervix	CC	cellular response to abiotic stimulus	69/2311	331/18723	7.36e-06	1.73e-04	69
GO:01040048	Cervix	CC	cellular response to environmental stimulus	69/2311	331/18723	7.36e-06	1.73e-04	69
GO:00064708	Cervix	CC	protein dephosphorylation	60/2311	281/18723	1.33e-05	2.68e-04	60
GO:00512713	Cervix	CC	negative regulation of cellular component movement	73/2311	367/18723	2.22e-05	3.95e-04	73
GO:00400133	Cervix	CC	negative regulation of locomotion	76/2311	391/18723	3.47e-05	5.60e-04	76
GO:20001463	Cervix	CC	negative regulation of cell motility	71/2311	359/18723	3.47e-05	5.60e-04	71
GO:00093149	Cervix	CC	response to radiation	86/2311	456/18723	3.50e-05	5.63e-04	86

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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

PTPRK

SNV

Missense_Mutation

c.4103N>A

p.Pro1368His

p.P1368H

Q15262

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-A2-A25A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Cytoxan

PTPRK

SNV

Missense_Mutation

novel

c.1970N>A

p.Thr657Lys

p.T657K

Q15262

protein_coding

deleterious(0.02)

benign(0.15)

TCGA-A7-A3IZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

PTPRK

SNV

Missense_Mutation

rs372899705

c.2630N>T

p.Thr877Ile

p.T877I

Q15262

protein_coding

deleterious(0)

probably_damaging(0.979)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PTPRK

SNV

Missense_Mutation

c.1345N>T

p.Ala449Ser

p.A449S

Q15262

protein_coding

tolerated(1)

benign(0.099)

TCGA-BH-A0EB-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

PTPRK

SNV

Missense_Mutation

c.3706G>A

p.Asp1236Asn

p.D1236N

Q15262

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-GM-A2D9-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

PTPRK

SNV

Missense_Mutation

rs375206155

c.2650N>G

p.Ile884Val

p.I884V

Q15262

protein_coding

tolerated(0.6)

benign(0.001)

TCGA-PE-A5DD-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

PTPRK

insertion

Frame_Shift_Ins

novel

c.3787_3788insGAGG

p.Gln1263ArgfsTer26

p.Q1263Rfs*26

Q15262

protein_coding

TCGA-AO-A03R-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

PTPRK

insertion

Frame_Shift_Ins

novel

c.3786_3787insTGGAAAAGTGGCAGGAGGAATG

p.Gln1263TrpfsTer32

p.Q1263Wfs*32

Q15262

protein_coding

TCGA-AO-A03R-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

PTPRK

insertion

Frame_Shift_Ins

novel

c.315_316insTT

p.Ile106LeufsTer14

p.I106Lfs*14

Q15262

protein_coding

TCGA-AQ-A04J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

PTPRK

insertion

Frame_Shift_Ins

novel

c.314_315insGTGGTTTGACAAAGAGCTA

p.Cys105TrpfsTer9

p.C105Wfs*9

Q15262

protein_coding

TCGA-AQ-A04J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

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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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