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: PTK2B

Gene summary for PTK2B

Gene summary.

Gene information	Species	Human
	Gene symbol	PTK2B
	Gene ID	2185
	Gene name	protein tyrosine kinase 2 beta
	Gene Alias	CADTK
	Cytomap	8p21.2
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	Q14289

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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
2185	PTK2B	HTA11_2487_2000001011	Human	Colorectum	SER	8.25e-06	5.90e-01	-0.1808
2185	PTK2B	HTA11_347_2000001011	Human	Colorectum	AD	6.10e-16	6.59e-01	-0.1954
2185	PTK2B	HTA11_411_2000001011	Human	Colorectum	SER	1.25e-02	9.86e-01	-0.2602
2185	PTK2B	HTA11_696_2000001011	Human	Colorectum	AD	5.38e-07	5.24e-01	-0.1464
2185	PTK2B	HTA11_5212_2000001011	Human	Colorectum	AD	1.58e-08	6.99e-01	-0.2061
2185	PTK2B	A002-C-010	Human	Colorectum	FAP	2.35e-02	-1.14e-01	0.242
2185	PTK2B	A015-C-203	Human	Colorectum	FAP	1.71e-12	-2.25e-01	-0.1294
2185	PTK2B	A002-C-201	Human	Colorectum	FAP	2.31e-07	-2.72e-01	0.0324
2185	PTK2B	A001-C-108	Human	Colorectum	FAP	2.83e-06	-1.79e-01	-0.0272
2185	PTK2B	A002-C-205	Human	Colorectum	FAP	4.14e-09	-2.83e-01	-0.1236
2185	PTK2B	A015-C-006	Human	Colorectum	FAP	1.68e-06	-3.26e-01	-0.0994
2185	PTK2B	A015-C-106	Human	Colorectum	FAP	7.52e-05	-1.92e-01	-0.0511
2185	PTK2B	A002-C-114	Human	Colorectum	FAP	2.54e-05	-1.66e-01	-0.1561
2185	PTK2B	A015-C-104	Human	Colorectum	FAP	4.67e-14	-2.76e-01	-0.1899
2185	PTK2B	A001-C-014	Human	Colorectum	FAP	1.78e-05	-1.58e-01	0.0135
2185	PTK2B	A002-C-016	Human	Colorectum	FAP	4.31e-08	-2.27e-01	0.0521
2185	PTK2B	A015-C-002	Human	Colorectum	FAP	1.16e-03	-2.64e-01	-0.0763
2185	PTK2B	A001-C-203	Human	Colorectum	FAP	4.27e-03	-1.87e-01	-0.0481
2185	PTK2B	A002-C-116	Human	Colorectum	FAP	6.16e-10	-2.26e-01	-0.0452
2185	PTK2B	A014-C-008	Human	Colorectum	FAP	3.49e-04	-2.56e-01	-0.191

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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
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
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:20004013	Oral cavity	OSCC	regulation of lymphocyte migration	34/7305	61/18723	5.90e-03	2.25e-02	34
GO:00509204	Oral cavity	OSCC	regulation of chemotaxis	105/7305	223/18723	8.27e-03	3.01e-02	105
GO:00434107	Oral cavity	OSCC	positive regulation of MAPK cascade	213/7305	480/18723	8.71e-03	3.16e-02	213
GO:19055213	Oral cavity	OSCC	regulation of macrophage migration	24/7305	41/18723	8.81e-03	3.19e-02	24
GO:00435062	Oral cavity	OSCC	regulation of JUN kinase activity	32/7305	58/18723	9.08e-03	3.26e-02	32
GO:20002496	Oral cavity	OSCC	regulation of actin cytoskeleton reorganization	23/7305	39/18723	9.09e-03	3.26e-02	23
GO:200105715	Oral cavity	OSCC	reactive nitrogen species metabolic process	43/7305	82/18723	9.20e-03	3.30e-02	43
GO:00487713	Oral cavity	OSCC	tissue remodeling	84/7305	175/18723	9.39e-03	3.36e-02	84
GO:00703716	Oral cavity	OSCC	ERK1 and ERK2 cascade	150/7305	330/18723	9.47e-03	3.38e-02	150
GO:003103217	Oral cavity	OSCC	actomyosin structure organization	93/7305	196/18723	9.63e-03	3.41e-02	93
GO:00442625	Oral cavity	OSCC	cellular carbohydrate metabolic process	130/7305	283/18723	9.98e-03	3.49e-02	130
GO:00463301	Oral cavity	OSCC	positive regulation of JNK cascade	46/7305	89/18723	1.01e-02	3.50e-02	46
GO:0032526	Oral cavity	OSCC	response to retinoic acid	54/7305	107/18723	1.04e-02	3.54e-02	54
GO:0045453	Oral cavity	OSCC	bone resorption	35/7305	65/18723	1.07e-02	3.64e-02	35
GO:004620915	Oral cavity	OSCC	nitric oxide metabolic process	42/7305	81/18723	1.27e-02	4.24e-02	42
GO:00703724	Oral cavity	OSCC	regulation of ERK1 and ERK2 cascade	140/7305	309/18723	1.34e-02	4.46e-02	140
GO:00454298	Oral cavity	OSCC	positive regulation of nitric oxide biosynthetic process	23/7305	40/18723	1.36e-02	4.50e-02	23
GO:19055175	Oral cavity	OSCC	macrophage migration	30/7305	55/18723	1.39e-02	4.59e-02	30
GO:0032770	Oral cavity	OSCC	positive regulation of monooxygenase activity	20/7305	34/18723	1.51e-02	4.91e-02	20
GO:004325426	Oral cavity	EOLP	regulation of protein-containing complex assembly	112/2218	428/18723	1.58e-16	1.35e-13	112

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05135	Colorectum	AD	Yersinia infection	58/2092	137/8465	3.90e-06	4.35e-05	2.78e-05	58
hsa05170	Colorectum	AD	Human immunodeficiency virus 1 infection	72/2092	212/8465	1.40e-03	8.46e-03	5.39e-03	72
hsa05163	Colorectum	AD	Human cytomegalovirus infection	75/2092	225/8465	2.00e-03	1.10e-02	7.01e-03	75
hsa051351	Colorectum	AD	Yersinia infection	58/2092	137/8465	3.90e-06	4.35e-05	2.78e-05	58
hsa051701	Colorectum	AD	Human immunodeficiency virus 1 infection	72/2092	212/8465	1.40e-03	8.46e-03	5.39e-03	72
hsa051631	Colorectum	AD	Human cytomegalovirus infection	75/2092	225/8465	2.00e-03	1.10e-02	7.01e-03	75
hsa051352	Colorectum	SER	Yersinia infection	43/1580	137/8465	2.15e-04	2.10e-03	1.52e-03	43
hsa046702	Colorectum	SER	Leukocyte transendothelial migration	37/1580	114/8465	2.77e-04	2.56e-03	1.86e-03	37
hsa051702	Colorectum	SER	Human immunodeficiency virus 1 infection	58/1580	212/8465	1.08e-03	8.56e-03	6.21e-03	58
hsa051632	Colorectum	SER	Human cytomegalovirus infection	57/1580	225/8465	7.40e-03	3.84e-02	2.79e-02	57
hsa049122	Colorectum	SER	GnRH signaling pathway	27/1580	93/8465	9.68e-03	4.72e-02	3.43e-02	27
hsa051353	Colorectum	SER	Yersinia infection	43/1580	137/8465	2.15e-04	2.10e-03	1.52e-03	43
hsa046703	Colorectum	SER	Leukocyte transendothelial migration	37/1580	114/8465	2.77e-04	2.56e-03	1.86e-03	37
hsa051703	Colorectum	SER	Human immunodeficiency virus 1 infection	58/1580	212/8465	1.08e-03	8.56e-03	6.21e-03	58
hsa051633	Colorectum	SER	Human cytomegalovirus infection	57/1580	225/8465	7.40e-03	3.84e-02	2.79e-02	57
hsa049123	Colorectum	SER	GnRH signaling pathway	27/1580	93/8465	9.68e-03	4.72e-02	3.43e-02	27
hsa051356	Colorectum	FAP	Yersinia infection	43/1404	137/8465	1.21e-05	1.62e-04	9.86e-05	43
hsa046706	Colorectum	FAP	Leukocyte transendothelial migration	37/1404	114/8465	2.12e-05	2.53e-04	1.54e-04	37
hsa049126	Colorectum	FAP	GnRH signaling pathway	28/1404	93/8465	8.16e-04	5.14e-03	3.13e-03	28
hsa051636	Colorectum	FAP	Human cytomegalovirus infection	55/1404	225/8465	1.42e-03	7.67e-03	4.67e-03	55

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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

PTK2B

SNV

Missense_Mutation

c.2871N>A

p.Met957Ile

p.M957I

Q14289

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A2-A0T2-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

xeloda

PTK2B

SNV

Missense_Mutation

rs750561555

c.553N>T

p.Arg185Trp

p.R185W

Q14289

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A2-A3XS-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

PTK2B

SNV

Missense_Mutation

c.973N>C

p.Glu325Gln

p.E325Q

Q14289

protein_coding

tolerated(0.24)

benign(0.044)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PTK2B

SNV

Missense_Mutation

c.1817G>T

p.Ser606Ile

p.S606I

Q14289

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PTK2B

SNV

Missense_Mutation

c.1681N>C

p.Glu561Gln

p.E561Q

Q14289

protein_coding

tolerated(0.06)

benign(0.006)

TCGA-C8-A12T-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PTK2B

insertion

In_Frame_Ins

novel

c.2331_2332insCGGTGTCCCATGGTCCTATATTTGTTCTCAAGGAAATGCCTG

p.His777_Ser778insArgCysProMetValLeuTyrLeuPheSerArgLysCysLeu

p.H777_S778insRCPMVLYLFSRKCL

Q14289

protein_coding

TCGA-B6-A0RG-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PTK2B

insertion

Frame_Shift_Ins

novel

c.789_790insGTCATAGATC

p.Thr264ValfsTer8

p.T264Vfs*8

Q14289

protein_coding

TCGA-BH-A0H7-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

doxorubicin

PTK2B

insertion

Frame_Shift_Ins

novel

c.2148_2148+1insGTAAGCCAAGCCATGT

p.Pro717ValfsTer10

p.P717Vfs*10

Q14289

protein_coding

TCGA-GM-A2D9-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

PTK2B

SNV

Missense_Mutation

novel

c.1757G>A

p.Arg586His

p.R586H

Q14289

protein_coding

deleterious(0)

possibly_damaging(0.854)

TCGA-EA-A410-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

PTK2B

SNV

Missense_Mutation

rs773709584

c.2779N>A

p.Leu927Ile

p.L927I

Q14289

protein_coding

tolerated(1)

benign(0)

TCGA-FU-A3HZ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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
2185	PTK2B	DRUGGABLE GENOME, KINASE, ION CHANNEL, G PROTEIN COUPLED RECEPTOR, TYROSINE KINASE, ENZYME		PMID27774822-Compound-Figure10Example1
2185	PTK2B	DRUGGABLE GENOME, KINASE, ION CHANNEL, G PROTEIN COUPLED RECEPTOR, TYROSINE KINASE, ENZYME		Imidazo[4,5-c]pyridine derivative 1
2185	PTK2B	DRUGGABLE GENOME, KINASE, ION CHANNEL, G PROTEIN COUPLED RECEPTOR, TYROSINE KINASE, ENZYME		Aminotriazolopyridine derivative 1
2185	PTK2B	DRUGGABLE GENOME, KINASE, ION CHANNEL, G PROTEIN COUPLED RECEPTOR, TYROSINE KINASE, ENZYME		CID 94381	CHEMBL374632
2185	PTK2B	DRUGGABLE GENOME, KINASE, ION CHANNEL, G PROTEIN COUPLED RECEPTOR, TYROSINE KINASE, ENZYME		HTS-05058	CHEMBL261692
2185	PTK2B	DRUGGABLE GENOME, KINASE, ION CHANNEL, G PROTEIN COUPLED RECEPTOR, TYROSINE KINASE, ENZYME		PMID27774824-Compound-Figure11Example1up
2185	PTK2B	DRUGGABLE GENOME, KINASE, ION CHANNEL, G PROTEIN COUPLED RECEPTOR, TYROSINE KINASE, ENZYME		TCMDC-125185	CHEMBL580819
2185	PTK2B	DRUGGABLE GENOME, KINASE, ION CHANNEL, G PROTEIN COUPLED RECEPTOR, TYROSINE KINASE, ENZYME	inhibitor	CHEMBL3137331	DEFACTINIB
2185	PTK2B	DRUGGABLE GENOME, KINASE, ION CHANNEL, G PROTEIN COUPLED RECEPTOR, TYROSINE KINASE, ENZYME		PF-04965842	ABROCITINIB
2185	PTK2B	DRUGGABLE GENOME, KINASE, ION CHANNEL, G PROTEIN COUPLED RECEPTOR, TYROSINE KINASE, ENZYME		ASP-015K	PEFICITINIB

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