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: PTPRE

Gene summary for PTPRE

Gene summary.

Gene information	Species	Human
	Gene symbol	PTPRE
	Gene ID	5791
	Gene name	protein tyrosine phosphatase receptor type E
	Gene Alias	HPTPE
	Cytomap	10q26.2
	Gene Type	protein-coding
	GO ID	GO:0006464
	UniProtAcc	P23469

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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
5791	PTPRE	LZE4T	Human	Esophagus	ESCC	1.31e-05	-1.13e-02	0.0811
5791	PTPRE	LZE6T	Human	Esophagus	ESCC	1.03e-03	-5.80e-03	0.0845
5791	PTPRE	P2T-E	Human	Esophagus	ESCC	2.48e-16	8.44e-02	0.1177
5791	PTPRE	P4T-E	Human	Esophagus	ESCC	2.91e-05	6.04e-02	0.1323
5791	PTPRE	P5T-E	Human	Esophagus	ESCC	4.53e-13	2.34e-01	0.1327
5791	PTPRE	P8T-E	Human	Esophagus	ESCC	2.62e-07	2.65e-01	0.0889
5791	PTPRE	P9T-E	Human	Esophagus	ESCC	1.14e-04	5.92e-02	0.1131
5791	PTPRE	P10T-E	Human	Esophagus	ESCC	1.94e-07	-9.61e-02	0.116
5791	PTPRE	P11T-E	Human	Esophagus	ESCC	7.55e-13	7.71e-01	0.1426
5791	PTPRE	P12T-E	Human	Esophagus	ESCC	1.30e-12	-4.00e-02	0.1122
5791	PTPRE	P15T-E	Human	Esophagus	ESCC	3.33e-04	-1.90e-02	0.1149
5791	PTPRE	P16T-E	Human	Esophagus	ESCC	1.98e-09	2.14e-01	0.1153
5791	PTPRE	P19T-E	Human	Esophagus	ESCC	5.61e-03	5.51e-01	0.1662
5791	PTPRE	P21T-E	Human	Esophagus	ESCC	2.72e-13	1.88e-01	0.1617
5791	PTPRE	P22T-E	Human	Esophagus	ESCC	2.01e-05	-7.45e-02	0.1236
5791	PTPRE	P23T-E	Human	Esophagus	ESCC	1.87e-04	2.73e-02	0.108
5791	PTPRE	P24T-E	Human	Esophagus	ESCC	3.52e-09	1.32e-01	0.1287
5791	PTPRE	P26T-E	Human	Esophagus	ESCC	9.21e-08	2.37e-01	0.1276
5791	PTPRE	P27T-E	Human	Esophagus	ESCC	2.78e-11	5.55e-02	0.1055
5791	PTPRE	P28T-E	Human	Esophagus	ESCC	4.51e-10	2.07e-01	0.1149

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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:001631110	Esophagus	ESCC	dephosphorylation	251/8552	417/18723	1.26e-09	2.99e-08	251
GO:000647018	Esophagus	ESCC	protein dephosphorylation	177/8552	281/18723	3.13e-09	6.72e-08	177
GO:190165319	Esophagus	ESCC	cellular response to peptide	208/8552	359/18723	1.68e-06	2.01e-05	208
GO:0043434111	Esophagus	ESCC	response to peptide hormone	234/8552	414/18723	4.93e-06	5.21e-05	234
GO:003286918	Esophagus	ESCC	cellular response to insulin stimulus	124/8552	203/18723	6.63e-06	6.75e-05	124
GO:003286818	Esophagus	ESCC	response to insulin	156/8552	264/18723	7.21e-06	7.20e-05	156
GO:007137516	Esophagus	ESCC	cellular response to peptide hormone stimulus	166/8552	290/18723	4.48e-05	3.55e-04	166
GO:00082869	Esophagus	ESCC	insulin receptor signaling pathway	66/8552	116/18723	9.76e-03	3.37e-02	66
GO:003286821	Liver	HCC	response to insulin	172/7958	264/18723	7.14e-14	4.23e-12	172
GO:003286921	Liver	HCC	cellular response to insulin stimulus	137/7958	203/18723	4.69e-13	2.44e-11	137
GO:004343422	Liver	HCC	response to peptide hormone	247/7958	414/18723	9.55e-13	4.77e-11	247
GO:007137521	Liver	HCC	cellular response to peptide hormone stimulus	179/7958	290/18723	2.54e-11	9.88e-10	179
GO:190165321	Liver	HCC	cellular response to peptide	211/7958	359/18723	2.86e-10	9.63e-09	211
GO:00082862	Liver	HCC	insulin receptor signaling pathway	78/7958	116/18723	6.15e-08	1.29e-06	78
GO:001631121	Liver	HCC	dephosphorylation	230/7958	417/18723	1.00e-07	1.96e-06	230
GO:000647021	Liver	HCC	protein dephosphorylation	162/7958	281/18723	1.91e-07	3.46e-06	162
GO:19000762	Liver	HCC	regulation of cellular response to insulin stimulus	43/7958	64/18723	5.73e-05	5.31e-04	43
GO:00466261	Liver	HCC	regulation of insulin receptor signaling pathway	43/7958	66/18723	1.69e-04	1.34e-03	43
GO:0046627	Liver	HCC	negative regulation of insulin receptor signaling pathway	22/7958	35/18723	1.21e-02	4.41e-02	22
GO:1900077	Liver	HCC	negative regulation of cellular response to insulin stimulus	23/7958	37/18723	1.25e-02	4.53e-02	23

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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

PTPRE

SNV

Missense_Mutation

novel

c.680C>T

p.Ser227Phe

p.S227F

P23469

protein_coding

deleterious(0)

probably_damaging(0.978)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

PTPRE

SNV

Missense_Mutation

rs765453483

c.1954G>T

p.Ala652Ser

p.A652S

P23469

protein_coding

tolerated(0.31)

possibly_damaging(0.866)

TCGA-A2-A25C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

PTPRE

SNV

Missense_Mutation

c.178N>T

p.Leu60Phe

p.L60F

P23469

protein_coding

tolerated(0.8)

benign(0.112)

TCGA-A7-A26J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

PTPRE

SNV

Missense_Mutation

rs765453483

c.1954N>T

p.Ala652Ser

p.A652S

P23469

protein_coding

tolerated(0.31)

possibly_damaging(0.866)

TCGA-AC-A3TM-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

PTPRE

SNV

Missense_Mutation

novel

c.628N>T

p.Pro210Ser

p.P210S

P23469

protein_coding

deleterious(0.03)

probably_damaging(0.999)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

PTPRE

SNV

Missense_Mutation

c.904C>T

p.Pro302Ser

p.P302S

P23469

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PTPRE

SNV

Missense_Mutation

rs753495289

c.1754N>A

p.Arg585Gln

p.R585Q

P23469

protein_coding

deleterious(0.01)

possibly_damaging(0.655)

TCGA-E2-A158-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

arimidex

PTPRE

SNV

Missense_Mutation

rs143577888

c.853N>A

p.Asp285Asn

p.D285N

P23469

protein_coding

tolerated(0.57)

benign(0.201)

TCGA-EW-A1J5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

PTPRE

SNV

Missense_Mutation

novel

c.708N>C

p.Leu236Phe

p.L236F

P23469

protein_coding

deleterious(0)

possibly_damaging(0.761)

TCGA-C5-A7X5-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

carboplatin

PTPRE

SNV

Missense_Mutation

novel

c.193G>C

p.Ala65Pro

p.A65P

P23469

protein_coding

deleterious(0.02)

benign(0.21)

TCGA-VS-A8EK-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

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