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	CA_HPV_3	Human	Cervix	CC	2.06e-03	1.32e-01	0.0414
5796	PTPRK	CCI_1	Human	Cervix	CC	1.36e-26	2.41e+00	0.528
5796	PTPRK	CCI_2	Human	Cervix	CC	9.01e-23	2.54e+00	0.5249
5796	PTPRK	CCI_3	Human	Cervix	CC	1.89e-43	2.40e+00	0.516
5796	PTPRK	CCII_1	Human	Cervix	CC	2.70e-12	5.84e-01	0.3249
5796	PTPRK	Tumor	Human	Cervix	CC	4.81e-04	1.88e-01	0.1241
5796	PTPRK	sample3	Human	Cervix	CC	2.99e-08	2.93e-01	0.1387
5796	PTPRK	T3	Human	Cervix	CC	5.23e-11	3.04e-01	0.1389
5796	PTPRK	HTA11_3410_2000001011	Human	Colorectum	AD	1.74e-46	-7.97e-01	0.0155
5796	PTPRK	HTA11_2951_2000001011	Human	Colorectum	AD	3.80e-12	-8.27e-01	0.0216
5796	PTPRK	HTA11_347_2000001011	Human	Colorectum	AD	6.34e-14	6.22e-01	-0.1954
5796	PTPRK	HTA11_3361_2000001011	Human	Colorectum	AD	1.36e-25	-7.88e-01	-0.1207
5796	PTPRK	HTA11_696_2000001011	Human	Colorectum	AD	3.81e-04	-3.56e-01	-0.1464
5796	PTPRK	HTA11_5212_2000001011	Human	Colorectum	AD	1.11e-08	-5.71e-01	-0.2061
5796	PTPRK	HTA11_5216_2000001011	Human	Colorectum	SER	8.56e-09	-5.82e-01	-0.1462
5796	PTPRK	HTA11_9341_2000001011	Human	Colorectum	SER	4.85e-12	-7.07e-01	-0.00410000000000005
5796	PTPRK	HTA11_7862_2000001011	Human	Colorectum	AD	1.02e-04	-4.11e-01	-0.0179
5796	PTPRK	HTA11_866_3004761011	Human	Colorectum	AD	5.96e-21	-7.46e-01	0.096
5796	PTPRK	HTA11_4255_2000001011	Human	Colorectum	SER	7.05e-09	-3.99e-01	0.0446
5796	PTPRK	HTA11_9408_2000001011	Human	Colorectum	AD	7.22e-13	-1.00e+00	0.0451

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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:00621976	Stomach	GC	cellular response to chemical stress	44/1159	337/18723	2.24e-06	9.73e-05	44
GO:00003026	Stomach	GC	response to reactive oxygen species	32/1159	222/18723	6.94e-06	2.57e-04	32
GO:00345996	Stomach	GC	cellular response to oxidative stress	38/1159	288/18723	8.45e-06	2.96e-04	38
GO:0042110	Stomach	GC	T cell activation	53/1159	487/18723	4.56e-05	1.10e-03	53
GO:00346146	Stomach	GC	cellular response to reactive oxygen species	22/1159	155/18723	2.27e-04	3.83e-03	22
GO:00315895	Stomach	GC	cell-substrate adhesion	40/1159	363/18723	2.91e-04	4.68e-03	40
GO:0009314	Stomach	GC	response to radiation	47/1159	456/18723	4.21e-04	6.33e-03	47
GO:01501155	Stomach	GC	cell-substrate junction organization	15/1159	101/18723	1.35e-03	1.49e-02	15
GO:00506784	Stomach	GC	regulation of epithelial cell proliferation	39/1159	381/18723	1.42e-03	1.55e-02	39
GO:00343295	Stomach	GC	cell junction assembly	42/1159	420/18723	1.50e-03	1.62e-02	42
GO:00070445	Stomach	GC	cell-substrate junction assembly	14/1159	95/18723	2.07e-03	2.09e-02	14
GO:00712144	Stomach	GC	cellular response to abiotic stimulus	34/1159	331/18723	2.62e-03	2.45e-02	34
GO:01040044	Stomach	GC	cellular response to environmental stimulus	34/1159	331/18723	2.62e-03	2.45e-02	34
GO:00506734	Stomach	GC	epithelial cell proliferation	42/1159	437/18723	3.13e-03	2.78e-02	42
GO:00108374	Stomach	GC	regulation of keratinocyte proliferation	7/1159	35/18723	4.99e-03	3.96e-02	7
GO:00071605	Stomach	GC	cell-matrix adhesion	25/1159	233/18723	5.24e-03	4.11e-02	25
GO:000697911	Stomach	CAG with IM	response to oxidative stress	59/1050	446/18723	7.12e-10	1.02e-07	59
GO:006219711	Stomach	CAG with IM	cellular response to chemical stress	43/1050	337/18723	4.05e-07	2.34e-05	43
GO:003459911	Stomach	CAG with IM	cellular response to oxidative stress	37/1050	288/18723	2.19e-06	9.55e-05	37
GO:000030211	Stomach	CAG with IM	response to reactive oxygen species	31/1050	222/18723	2.54e-06	1.07e-04	31

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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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