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: PTK7

Gene summary for PTK7

Gene summary.

Gene information	Species	Human
	Gene symbol	PTK7
	Gene ID	5754
	Gene name	protein tyrosine kinase 7 (inactive)
	Gene Alias	CCK-4
	Cytomap	6p21.1
	Gene Type	protein-coding
	GO ID	GO:0001568
	UniProtAcc	Q13308

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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
5754	PTK7	HTA11_866_3004761011	Human	Colorectum	AD	1.95e-12	5.01e-01	0.096
5754	PTK7	HTA11_10711_2000001011	Human	Colorectum	AD	3.46e-10	6.96e-01	0.0338
5754	PTK7	HTA11_7696_3000711011	Human	Colorectum	AD	1.70e-08	4.01e-01	0.0674
5754	PTK7	HTA11_6818_2000001011	Human	Colorectum	AD	9.87e-03	3.85e-01	0.0112
5754	PTK7	HTA11_99999970781_79442	Human	Colorectum	MSS	2.30e-19	5.07e-01	0.294
5754	PTK7	HTA11_99999965104_69814	Human	Colorectum	MSS	2.24e-05	4.49e-01	0.281
5754	PTK7	HTA11_99999971662_82457	Human	Colorectum	MSS	6.66e-14	6.28e-01	0.3859
5754	PTK7	HTA11_99999973899_84307	Human	Colorectum	MSS	4.77e-13	8.53e-01	0.2585
5754	PTK7	HTA11_99999974143_84620	Human	Colorectum	MSS	7.98e-42	1.06e+00	0.3005
5754	PTK7	A001-C-119	Human	Colorectum	FAP	1.22e-04	5.10e-01	-0.1557
5754	PTK7	A002-C-021	Human	Colorectum	FAP	1.89e-08	4.21e-01	0.1171
5754	PTK7	CRC-1-8810	Human	Colorectum	CRC	1.98e-18	7.38e-01	0.6257
5754	PTK7	CRC-3-11773	Human	Colorectum	CRC	2.12e-06	4.57e-01	0.2564
5754	PTK7	LZE2T	Human	Esophagus	ESCC	1.19e-09	1.22e+00	0.082
5754	PTK7	LZE4T	Human	Esophagus	ESCC	7.51e-05	1.34e-01	0.0811
5754	PTK7	LZE24T	Human	Esophagus	ESCC	1.24e-07	1.29e-01	0.0596
5754	PTK7	P2T-E	Human	Esophagus	ESCC	4.73e-56	9.05e-01	0.1177
5754	PTK7	P4T-E	Human	Esophagus	ESCC	6.75e-32	6.55e-01	0.1323
5754	PTK7	P5T-E	Human	Esophagus	ESCC	6.87e-25	5.13e-01	0.1327
5754	PTK7	P8T-E	Human	Esophagus	ESCC	2.65e-13	2.29e-01	0.0889

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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
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:00303249	Esophagus	ESCC	lung development	109/8552	177/18723	1.40e-05	1.27e-04	109
GO:00017387	Esophagus	ESCC	morphogenesis of a polarized epithelium	63/8552	94/18723	2.34e-05	2.00e-04	63
GO:009026316	Esophagus	ESCC	positive regulation of canonical Wnt signaling pathway	69/8552	106/18723	4.22e-05	3.39e-04	69
GO:003017716	Esophagus	ESCC	positive regulation of Wnt signaling pathway	87/8552	140/18723	6.18e-05	4.73e-04	87
GO:009016216	Esophagus	ESCC	establishment of epithelial cell polarity	25/8552	31/18723	7.13e-05	5.38e-04	25
GO:00308595	Esophagus	ESCC	polarized epithelial cell differentiation	20/8552	24/18723	1.69e-04	1.11e-03	20
GO:00611625	Esophagus	ESCC	establishment of monopolar cell polarity	20/8552	24/18723	1.69e-04	1.11e-03	20
GO:001097516	Esophagus	ESCC	regulation of neuron projection development	240/8552	445/18723	2.48e-04	1.53e-03	240
GO:00613394	Esophagus	ESCC	establishment or maintenance of monopolar cell polarity	20/8552	25/18723	4.81e-04	2.69e-03	20
GO:00600714	Esophagus	ESCC	Wnt signaling pathway, planar cell polarity pathway	36/8552	52/18723	5.05e-04	2.79e-03	36
GO:00350893	Esophagus	ESCC	establishment of apical/basal cell polarity	18/8552	22/18723	5.69e-04	3.10e-03	18
GO:00485687	Esophagus	ESCC	embryonic organ development	228/8552	427/18723	7.28e-04	3.79e-03	228
GO:006056010	Esophagus	ESCC	developmental growth involved in morphogenesis	131/8552	234/18723	9.28e-04	4.73e-03	131
GO:00901753	Esophagus	ESCC	regulation of establishment of planar polarity	37/8552	56/18723	1.65e-03	7.65e-03	37
GO:0045198	Esophagus	ESCC	establishment of epithelial cell apical/basal polarity	14/8552	17/18723	2.22e-03	9.78e-03	14
GO:00017361	Esophagus	ESCC	establishment of planar polarity	45/8552	72/18723	2.97e-03	1.24e-02	45
GO:00071641	Esophagus	ESCC	establishment of tissue polarity	45/8552	72/18723	2.97e-03	1.24e-02	45
GO:00355671	Esophagus	ESCC	non-canonical Wnt signaling pathway	45/8552	72/18723	2.97e-03	1.24e-02	45
GO:00604856	Esophagus	ESCC	mesenchyme development	156/8552	291/18723	3.76e-03	1.53e-02	156
GO:00325261	Esophagus	ESCC	response to retinoic acid	63/8552	107/18723	4.05e-03	1.62e-02	63

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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

PTK7

SNV

Missense_Mutation

c.1028C>A

p.Ala343Asp

p.A343D

Q13308

protein_coding

deleterious(0.01)

possibly_damaging(0.471)

TCGA-A2-A0D2-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

PTK7

SNV

Missense_Mutation

novel

c.2262N>A

p.Met754Ile

p.M754I

Q13308

protein_coding

deleterious(0.04)

benign(0.067)

TCGA-A7-A6VX-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

docetaxel

PTK7

SNV

Missense_Mutation

c.2124G>T

p.Lys708Asn

p.K708N

Q13308

protein_coding

deleterious(0.04)

benign(0.082)

TCGA-A8-A0A9-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

PTK7

SNV

Missense_Mutation

rs374956441

c.493C>T

p.Arg165Trp

p.R165W

Q13308

protein_coding

deleterious(0)

probably_damaging(0.983)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PTK7

SNV

Missense_Mutation

novel

c.2578N>C

p.Lys860Gln

p.K860Q

Q13308

protein_coding

deleterious(0)

possibly_damaging(0.734)

TCGA-B6-A0IN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PTK7

SNV

Missense_Mutation

c.2317G>A

p.Glu773Lys

p.E773K

Q13308

protein_coding

deleterious(0.03)

benign(0.119)

TCGA-D8-A1JN-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozolum

PTK7

SNV

Missense_Mutation

novel

c.1769N>T

p.Ala590Val

p.A590V

Q13308

protein_coding

deleterious(0.01)

possibly_damaging(0.475)

TCGA-E9-A228-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

PTK7

SNV

Missense_Mutation

rs767634504

c.581N>T

p.Thr194Met

p.T194M

Q13308

protein_coding

deleterious(0.03)

benign(0.104)

TCGA-S3-AA14-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

PTK7

insertion

In_Frame_Ins

novel

c.2208_2209insGATCTGGGCCCAAACAGAGTCCGGTTTGGCAGACGTGGAATGTCA

p.Lys736_Arg737insAspLeuGlyProAsnArgValArgPheGlyArgArgGlyMetSer

p.K736_R737insDLGPNRVRFGRRGMS

Q13308

protein_coding

TCGA-AO-A0J9-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

PTK7

insertion

Frame_Shift_Ins

novel

c.2577_2578insCTTCC

p.Lys860LeufsTer4

p.K860Lfs*4

Q13308

protein_coding

TCGA-B6-A0IN-01

Breast

breast invasive carcinoma

Female

<65

I/II

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
5754	PTK7	DRUGGABLE GENOME, KINASE, TYROSINE KINASE, CLINICALLY ACTIONABLE		PF-06647020	COFETUZUMAB PELIDOTIN

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