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: PTPRA

Gene summary for PTPRA

Gene summary.

Gene information	Species	Human
	Gene symbol	PTPRA
	Gene ID	5786
	Gene name	protein tyrosine phosphatase receptor type A
	Gene Alias	HEPTP
	Cytomap	20p13
	Gene Type	protein-coding
	GO ID	GO:0001952
	UniProtAcc	P18433

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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
5786	PTPRA	CA_HPV_1	Human	Cervix	CC	5.39e-03	4.68e-02	0.0264
5786	PTPRA	CCI_2	Human	Cervix	CC	4.95e-04	7.87e-01	0.5249
5786	PTPRA	CCI_3	Human	Cervix	CC	3.72e-05	5.40e-01	0.516
5786	PTPRA	LZE2T	Human	Esophagus	ESCC	1.52e-02	5.89e-01	0.082
5786	PTPRA	LZE4T	Human	Esophagus	ESCC	7.35e-03	2.51e-02	0.0811
5786	PTPRA	LZE5T	Human	Esophagus	ESCC	1.45e-04	2.02e-01	0.0514
5786	PTPRA	LZE20T	Human	Esophagus	ESCC	4.30e-08	3.03e-01	0.0662
5786	PTPRA	LZE21D1	Human	Esophagus	HGIN	3.18e-03	1.91e-01	0.0632
5786	PTPRA	LZE22T	Human	Esophagus	ESCC	1.07e-04	2.02e-01	0.068
5786	PTPRA	LZE24T	Human	Esophagus	ESCC	3.57e-21	2.85e-01	0.0596
5786	PTPRA	P1T-E	Human	Esophagus	ESCC	2.29e-18	8.72e-01	0.0875
5786	PTPRA	P2T-E	Human	Esophagus	ESCC	1.87e-44	7.83e-01	0.1177
5786	PTPRA	P4T-E	Human	Esophagus	ESCC	1.21e-32	7.05e-01	0.1323
5786	PTPRA	P5T-E	Human	Esophagus	ESCC	2.07e-08	1.58e-01	0.1327
5786	PTPRA	P8T-E	Human	Esophagus	ESCC	5.11e-34	5.70e-01	0.0889
5786	PTPRA	P9T-E	Human	Esophagus	ESCC	1.91e-21	3.99e-01	0.1131
5786	PTPRA	P10T-E	Human	Esophagus	ESCC	1.32e-49	9.23e-01	0.116
5786	PTPRA	P11T-E	Human	Esophagus	ESCC	1.58e-12	6.20e-01	0.1426
5786	PTPRA	P12T-E	Human	Esophagus	ESCC	2.36e-33	6.71e-01	0.1122
5786	PTPRA	P15T-E	Human	Esophagus	ESCC	7.68e-24	4.07e-01	0.1149

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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
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
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: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:01501159	Cervix	CC	cell-substrate junction organization	37/2311	101/18723	3.20e-10	4.46e-08	37
GO:00070448	Cervix	CC	cell-substrate junction assembly	34/2311	95/18723	3.35e-09	3.45e-07	34
GO:00019528	Cervix	CC	regulation of cell-matrix adhesion	40/2311	128/18723	1.32e-08	1.04e-06	40
GO:00071608	Cervix	CC	cell-matrix adhesion	60/2311	233/18723	1.58e-08	1.23e-06	60
GO:00072295	Cervix	CC	integrin-mediated signaling pathway	34/2311	107/18723	1.01e-07	5.25e-06	34
GO:00343298	Cervix	CC	cell junction assembly	88/2311	420/18723	3.42e-07	1.38e-05	88
GO:01501169	Cervix	CC	regulation of cell-substrate junction organization	25/2311	71/18723	5.58e-07	2.06e-05	25
GO:00480417	Cervix	CC	focal adhesion assembly	28/2311	87/18723	9.86e-07	3.45e-05	28
GO:00518938	Cervix	CC	regulation of focal adhesion assembly	22/2311	66/18723	7.37e-06	1.73e-04	22
GO:00901098	Cervix	CC	regulation of cell-substrate junction assembly	22/2311	66/18723	7.37e-06	1.73e-04	22
GO:00064708	Cervix	CC	protein dephosphorylation	60/2311	281/18723	1.33e-05	2.68e-04	60
GO:19016538	Cervix	CC	cellular response to peptide	72/2311	359/18723	1.89e-05	3.48e-04	72
GO:00434349	Cervix	CC	response to peptide hormone	77/2311	414/18723	1.40e-04	1.70e-03	77
GO:00713757	Cervix	CC	cellular response to peptide hormone stimulus	57/2311	290/18723	2.32e-04	2.59e-03	57
GO:00328698	Cervix	CC	cellular response to insulin stimulus	42/2311	203/18723	4.95e-04	4.83e-03	42
GO:19018886	Cervix	CC	regulation of cell junction assembly	42/2311	204/18723	5.50e-04	5.29e-03	42
GO:00163117	Cervix	CC	dephosphorylation	73/2311	417/18723	1.23e-03	9.87e-03	73
GO:00328688	Cervix	CC	response to insulin	50/2311	264/18723	1.28e-03	1.02e-02	50

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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

PTPRA

SNV

Missense_Mutation

rs758310508

c.12G>T

p.Trp4Cys

p.W4C

P18433

protein_coding

tolerated_low_confidence(0.1)

probably_damaging(0.99)

TCGA-A1-A0SP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

PTPRA

SNV

Missense_Mutation

novel

c.2377G>C

p.Asp793His

p.D793H

P18433

protein_coding

deleterious(0.04)

benign(0.25)

TCGA-A2-A0CL-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

PTPRA

SNV

Missense_Mutation

c.2064G>T

p.Gln688His

p.Q688H

P18433

protein_coding

tolerated(0.09)

benign(0.017)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PTPRA

SNV

Missense_Mutation

rs138944640

c.317C>T

p.Thr106Met

p.T106M

P18433

protein_coding

deleterious_low_confidence(0)

benign(0.212)

TCGA-AR-A2LQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

docetaxel

PTPRA

SNV

Missense_Mutation

c.742N>G

p.Leu248Val

p.L248V

P18433

protein_coding

tolerated(0.05)

benign(0.122)

TCGA-C8-A26V-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

tamoxiphen

PTPRA

SNV

Missense_Mutation

novel

c.2060G>A

p.Arg687Gln

p.R687Q

P18433

protein_coding

deleterious(0.01)

probably_damaging(0.943)

TCGA-E2-A15L-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

PTPRA

SNV

Missense_Mutation

c.1763A>T

p.Tyr588Phe

p.Y588F

P18433

protein_coding

deleterious(0.01)

probably_damaging(1)

TCGA-GM-A2DD-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

fluorouracil

PTPRA

SNV

Missense_Mutation

novel

c.790N>A

p.Glu264Lys

p.E264K

P18433

protein_coding

tolerated(0.29)

possibly_damaging(0.653)

TCGA-GM-A3XL-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

fluorouracil

PTPRA

insertion

Frame_Shift_Ins

novel

c.1686_1687insGGACACACTCCCTCCTA

p.Arg563GlyfsTer19

p.R563Gfs*19

P18433

protein_coding

TCGA-A7-A0CE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

PTPRA

insertion

Frame_Shift_Ins

novel

c.1688_1689insATGCTGGAATCCC

p.Val564CysfsTer12

p.V564Cfs*12

P18433

protein_coding

TCGA-A7-A0CE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

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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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