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: PTK2

Gene summary for PTK2

Gene summary.

Gene information	Species	Human
	Gene symbol	PTK2
	Gene ID	5747
	Gene name	protein tyrosine kinase 2
	Gene Alias	FADK
	Cytomap	8q24.3
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	Q05397

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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
5747	PTK2	CCI_1	Human	Cervix	CC	2.70e-19	1.59e+00	0.528
5747	PTK2	CCI_2	Human	Cervix	CC	1.85e-28	2.96e+00	0.5249
5747	PTK2	CCI_3	Human	Cervix	CC	2.32e-30	1.70e+00	0.516
5747	PTK2	CCII_1	Human	Cervix	CC	1.38e-18	8.72e-01	0.3249
5747	PTK2	HTA11_3410_2000001011	Human	Colorectum	AD	4.60e-25	-5.95e-01	0.0155
5747	PTK2	HTA11_2951_2000001011	Human	Colorectum	AD	7.64e-03	-5.45e-01	0.0216
5747	PTK2	HTA11_3361_2000001011	Human	Colorectum	AD	1.68e-07	-5.24e-01	-0.1207
5747	PTK2	HTA11_5212_2000001011	Human	Colorectum	AD	1.67e-03	-6.15e-01	-0.2061
5747	PTK2	HTA11_5216_2000001011	Human	Colorectum	SER	9.43e-10	-7.32e-01	-0.1462
5747	PTK2	HTA11_9341_2000001011	Human	Colorectum	SER	3.35e-04	-5.62e-01	-0.00410000000000005
5747	PTK2	HTA11_7862_2000001011	Human	Colorectum	AD	9.12e-07	-4.73e-01	-0.0179
5747	PTK2	HTA11_866_3004761011	Human	Colorectum	AD	2.76e-03	-3.99e-01	0.096
5747	PTK2	HTA11_9408_2000001011	Human	Colorectum	AD	9.98e-06	-9.26e-01	0.0451
5747	PTK2	HTA11_7696_3000711011	Human	Colorectum	AD	4.84e-04	-3.14e-01	0.0674
5747	PTK2	HTA11_11156_2000001011	Human	Colorectum	AD	3.00e-05	-6.35e-01	0.0397
5747	PTK2	HTA11_99999965062_69753	Human	Colorectum	MSI-H	2.14e-04	5.45e-01	0.3487
5747	PTK2	HTA11_99999965104_69814	Human	Colorectum	MSS	3.74e-18	7.66e-01	0.281
5747	PTK2	HTA11_99999971662_82457	Human	Colorectum	MSS	7.65e-03	5.47e-01	0.3859
5747	PTK2	F007	Human	Colorectum	FAP	2.35e-03	-1.44e-01	0.1176
5747	PTK2	A001-C-207	Human	Colorectum	FAP	3.11e-02	-8.54e-02	0.1278

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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
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:004217610	Cervix	CC	regulation of protein catabolic process	104/2311	391/18723	9.39e-15	9.36e-12	104
GO:004206010	Cervix	CC	wound healing	109/2311	422/18723	1.84e-14	1.57e-11	109
GO:001081010	Cervix	CC	regulation of cell-substrate adhesion	69/2311	221/18723	8.57e-14	5.69e-11	69
GO:00315898	Cervix	CC	cell-substrate adhesion	96/2311	363/18723	1.48e-13	8.85e-11	96
GO:002260410	Cervix	CC	regulation of cell morphogenesis	84/2311	309/18723	1.00e-12	4.29e-10	84
GO:004586210	Cervix	CC	positive regulation of proteolysis	95/2311	372/18723	1.84e-12	6.86e-10	95
GO:190336210	Cervix	CC	regulation of cellular protein catabolic process	72/2311	255/18723	5.98e-12	2.10e-09	72
GO:009013210	Cervix	CC	epithelium migration	90/2311	360/18723	2.45e-11	6.11e-09	90
GO:00016679	Cervix	CC	ameboidal-type cell migration	110/2311	475/18723	2.66e-11	6.36e-09	110
GO:001063110	Cervix	CC	epithelial cell migration	89/2311	357/18723	3.72e-11	8.54e-09	89
GO:00071639	Cervix	CC	establishment or maintenance of cell polarity	63/2311	218/18723	4.25e-11	8.76e-09	63
GO:009013010	Cervix	CC	tissue migration	90/2311	365/18723	5.42e-11	1.05e-08	90
GO:004573210	Cervix	CC	positive regulation of protein catabolic process	65/2311	231/18723	7.44e-11	1.39e-08	65
GO:002240710	Cervix	CC	regulation of cell-cell adhesion	103/2311	448/18723	1.78e-10	2.87e-08	103
GO:01501159	Cervix	CC	cell-substrate junction organization	37/2311	101/18723	3.20e-10	4.46e-08	37
GO:000989610	Cervix	CC	positive regulation of catabolic process	109/2311	492/18723	5.26e-10	6.99e-08	109
GO:190305010	Cervix	CC	regulation of proteolysis involved in cellular protein catabolic process	60/2311	221/18723	1.82e-09	1.98e-07	60
GO:00070448	Cervix	CC	cell-substrate junction assembly	34/2311	95/18723	3.35e-09	3.45e-07	34
GO:001063210	Cervix	CC	regulation of epithelial cell migration	72/2311	292/18723	4.52e-09	4.43e-07	72
GO:00321035	Cervix	CC	positive regulation of response to external stimulus	95/2311	427/18723	5.44e-09	5.03e-07	95

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0520820	Cervix	CC	Chemical carcinogenesis - reactive oxygen species	92/1267	223/8465	4.71e-22	5.09e-20	3.01e-20	92
hsa0541820	Cervix	CC	Fluid shear stress and atherosclerosis	50/1267	139/8465	5.71e-10	1.32e-08	7.81e-09	50
hsa0541720	Cervix	CC	Lipid and atherosclerosis	65/1267	215/8465	6.47e-09	1.10e-07	6.52e-08	65
hsa0516318	Cervix	CC	Human cytomegalovirus infection	65/1267	225/8465	4.59e-08	6.47e-07	3.83e-07	65
hsa0513120	Cervix	CC	Shigellosis	69/1267	247/8465	7.64e-08	1.03e-06	6.10e-07	69
hsa0520516	Cervix	CC	Proteoglycans in cancer	60/1267	205/8465	9.13e-08	1.18e-06	7.00e-07	60
hsa0451010	Cervix	CC	Focal adhesion	59/1267	203/8465	1.53e-07	1.84e-06	1.09e-06	59
hsa0481016	Cervix	CC	Regulation of actin cytoskeleton	64/1267	229/8465	2.24e-07	2.59e-06	1.53e-06	64
hsa0467020	Cervix	CC	Leukocyte transendothelial migration	36/1267	114/8465	5.22e-06	4.83e-05	2.86e-05	36
hsa0517016	Cervix	CC	Human immunodeficiency virus 1 infection	55/1267	212/8465	1.80e-05	1.42e-04	8.40e-05	55
hsa0401210	Cervix	CC	ErbB signaling pathway	28/1267	85/8465	2.40e-05	1.82e-04	1.08e-04	28
hsa0513516	Cervix	CC	Yersinia infection	39/1267	137/8465	3.27e-05	2.41e-04	1.42e-04	39
hsa052226	Cervix	CC	Small cell lung cancer	29/1267	92/8465	4.38e-05	3.09e-04	1.83e-04	29
hsa043609	Cervix	CC	Axon guidance	47/1267	182/8465	8.13e-05	5.38e-04	3.18e-04	47
hsa051657	Cervix	CC	Human papillomavirus infection	74/1267	331/8465	1.70e-04	1.02e-03	6.03e-04	74
hsa051465	Cervix	CC	Amoebiasis	29/1267	102/8465	3.31e-04	1.70e-03	1.01e-03	29
hsa015223	Cervix	CC	Endocrine resistance	28/1267	98/8465	3.82e-04	1.87e-03	1.11e-03	28
hsa0510020	Cervix	CC	Bacterial invasion of epithelial cells	23/1267	77/8465	6.25e-04	2.93e-03	1.73e-03	23
hsa04062	Cervix	CC	Chemokine signaling pathway	43/1267	192/8465	3.60e-03	1.34e-02	7.91e-03	43
hsa05208110	Cervix	CC	Chemical carcinogenesis - reactive oxygen species	92/1267	223/8465	4.71e-22	5.09e-20	3.01e-20	92

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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

PTK2

SNV

Missense_Mutation

c.1688N>T

p.Gly563Val

p.G563V

Q05397

protein_coding

deleterious(0.01)

probably_damaging(0.998)

TCGA-A2-A0T0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

PTK2

SNV

Missense_Mutation

rs542542126

c.2696N>T

p.Ala899Val

p.A899V

Q05397

protein_coding

tolerated(0.07)

possibly_damaging(0.652)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PTK2

SNV

Missense_Mutation

c.755N>T

p.Arg252Ile

p.R252I

Q05397

protein_coding

deleterious(0.02)

probably_damaging(0.996)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PTK2

SNV

Missense_Mutation

novel

c.1834A>G

p.Met612Val

p.M612V

Q05397

protein_coding

tolerated(0.09)

benign(0.001)

TCGA-AR-A0U0-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PTK2

SNV

Missense_Mutation

rs374554975

c.140G>A

p.Ser47Asn

p.S47N

Q05397

protein_coding

tolerated_low_confidence(0.21)

benign(0)

TCGA-BH-A18S-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PTK2

SNV

Missense_Mutation

c.121N>T

p.His41Tyr

p.H41Y

Q05397

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.998)

TCGA-C8-A1HM-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

PTK2

SNV

Missense_Mutation

c.1648N>T

p.Arg550Trp

p.R550W

Q05397

protein_coding

deleterious(0)

probably_damaging(0.974)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

PTK2

SNV

Missense_Mutation

novel

c.1166N>C

p.Val389Ala

p.V389A

Q05397

protein_coding

tolerated(0.33)

benign(0.412)

TCGA-D8-A73X-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

PTK2

SNV

Missense_Mutation

c.1790N>T

p.Arg597Leu

p.R597L

Q05397

protein_coding

deleterious(0)

probably_damaging(0.995)

TCGA-E9-A1RA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

PTK2

SNV

Missense_Mutation

c.1456N>G

p.Leu486Val

p.L486V

Q05397

protein_coding

deleterious(0)

benign(0.178)

TCGA-E9-A1RH-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

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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
5747	PTK2	TYROSINE KINASE, DRUGGABLE GENOME, KINASE, G PROTEIN COUPLED RECEPTOR, ENZYME		DNDI1417467	CHEMBL1997335
5747	PTK2	TYROSINE KINASE, DRUGGABLE GENOME, KINASE, G PROTEIN COUPLED RECEPTOR, ENZYME		SNS-314	SNS-314
5747	PTK2	TYROSINE KINASE, DRUGGABLE GENOME, KINASE, G PROTEIN COUPLED RECEPTOR, ENZYME	inhibitor	CHEMBL1084546	PF-00562271
5747	PTK2	TYROSINE KINASE, DRUGGABLE GENOME, KINASE, G PROTEIN COUPLED RECEPTOR, ENZYME		RG-1530	RG-1530
5747	PTK2	TYROSINE KINASE, DRUGGABLE GENOME, KINASE, G PROTEIN COUPLED RECEPTOR, ENZYME		BI-853520	BI-853520
5747	PTK2	TYROSINE KINASE, DRUGGABLE GENOME, KINASE, G PROTEIN COUPLED RECEPTOR, ENZYME		PF-562271	PF-00562271
5747	PTK2	TYROSINE KINASE, DRUGGABLE GENOME, KINASE, G PROTEIN COUPLED RECEPTOR, ENZYME		PF-04554878	DEFACTINIB
5747	PTK2	TYROSINE KINASE, DRUGGABLE GENOME, KINASE, G PROTEIN COUPLED RECEPTOR, ENZYME		GW843682X	GW843682X
5747	PTK2	TYROSINE KINASE, DRUGGABLE GENOME, KINASE, G PROTEIN COUPLED RECEPTOR, ENZYME	inhibitor	CHEMBL3544967	GSK-2256098
5747	PTK2	TYROSINE KINASE, DRUGGABLE GENOME, KINASE, G PROTEIN COUPLED RECEPTOR, ENZYME		1,2,4-triazolo[1,5a]pyridine derivative 1

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