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: PTPRH

Gene summary for PTPRH

Gene summary.

Gene information	Species	Human
	Gene symbol	PTPRH
	Gene ID	5794
	Gene name	protein tyrosine phosphatase receptor type H
	Gene Alias	R-PTP-H
	Cytomap	19q13.42
	Gene Type	protein-coding
	GO ID	GO:0001932
	UniProtAcc	NA

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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
5794	PTPRH	HTA11_2487_2000001011	Human	Colorectum	SER	7.50e-12	5.20e-01	-0.1808
5794	PTPRH	HTA11_1938_2000001011	Human	Colorectum	AD	5.89e-05	2.75e-01	-0.0811
5794	PTPRH	HTA11_347_2000001011	Human	Colorectum	AD	1.80e-13	4.99e-01	-0.1954
5794	PTPRH	HTA11_411_2000001011	Human	Colorectum	SER	5.36e-09	1.36e+00	-0.2602
5794	PTPRH	HTA11_2112_2000001011	Human	Colorectum	SER	1.01e-02	6.06e-01	-0.2196
5794	PTPRH	HTA11_696_2000001011	Human	Colorectum	AD	3.10e-07	4.25e-01	-0.1464
5794	PTPRH	HTA11_1391_2000001011	Human	Colorectum	AD	1.02e-02	2.74e-01	-0.059
5794	PTPRH	HTA11_5212_2000001011	Human	Colorectum	AD	3.27e-04	4.04e-01	-0.2061
5794	PTPRH	LZE24T	Human	Esophagus	ESCC	4.15e-02	9.96e-02	0.0596
5794	PTPRH	P1T-E	Human	Esophagus	ESCC	2.97e-02	3.41e-01	0.0875
5794	PTPRH	P8T-E	Human	Esophagus	ESCC	4.17e-05	1.57e-01	0.0889
5794	PTPRH	P23T-E	Human	Esophagus	ESCC	6.53e-09	2.36e-01	0.108
5794	PTPRH	P26T-E	Human	Esophagus	ESCC	4.41e-07	1.91e-01	0.1276
5794	PTPRH	P37T-E	Human	Esophagus	ESCC	4.27e-06	1.53e-01	0.1371
5794	PTPRH	P75T-E	Human	Esophagus	ESCC	1.62e-13	2.75e-01	0.1125
5794	PTPRH	P82T-E	Human	Esophagus	ESCC	1.51e-11	5.56e-01	0.1072
5794	PTPRH	P94T-E	Human	Esophagus	ESCC	1.38e-05	4.88e-01	0.0879
5794	PTPRH	P104T-E	Human	Esophagus	ESCC	3.26e-14	5.71e-01	0.0931
5794	PTPRH	P127T-E	Human	Esophagus	ESCC	7.76e-04	1.09e-01	0.0826
5794	PTPRH	P128T-E	Human	Esophagus	ESCC	1.29e-09	3.46e-01	0.1241

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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
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia

∗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:0010563	Colorectum	AD	negative regulation of phosphorus metabolic process	130/3918	442/18723	1.26e-05	2.76e-04	130
GO:0045936	Colorectum	AD	negative regulation of phosphate metabolic process	129/3918	441/18723	1.81e-05	3.76e-04	129
GO:0016311	Colorectum	AD	dephosphorylation	123/3918	417/18723	1.84e-05	3.82e-04	123
GO:0051348	Colorectum	AD	negative regulation of transferase activity	85/3918	268/18723	2.07e-05	4.19e-04	85
GO:0006470	Colorectum	AD	protein dephosphorylation	88/3918	281/18723	2.56e-05	4.89e-04	88
GO:0042326	Colorectum	AD	negative regulation of phosphorylation	112/3918	385/18723	8.02e-05	1.27e-03	112
GO:0001933	Colorectum	AD	negative regulation of protein phosphorylation	101/3918	342/18723	9.39e-05	1.42e-03	101
GO:0006469	Colorectum	AD	negative regulation of protein kinase activity	65/3918	212/18723	5.21e-04	5.62e-03	65
GO:0033673	Colorectum	AD	negative regulation of kinase activity	71/3918	237/18723	6.18e-04	6.47e-03	71
GO:00513481	Colorectum	SER	negative regulation of transferase activity	70/2897	268/18723	4.27e-06	1.62e-04	70
GO:00105631	Colorectum	SER	negative regulation of phosphorus metabolic process	101/2897	442/18723	2.39e-05	6.70e-04	101
GO:00459361	Colorectum	SER	negative regulation of phosphate metabolic process	100/2897	441/18723	3.62e-05	9.39e-04	100
GO:00019331	Colorectum	SER	negative regulation of protein phosphorylation	79/2897	342/18723	1.21e-04	2.49e-03	79
GO:00423261	Colorectum	SER	negative regulation of phosphorylation	86/2897	385/18723	2.10e-04	3.78e-03	86
GO:00336731	Colorectum	SER	negative regulation of kinase activity	57/2897	237/18723	3.48e-04	5.46e-03	57
GO:00064691	Colorectum	SER	negative regulation of protein kinase activity	52/2897	212/18723	3.75e-04	5.74e-03	52
GO:00064701	Colorectum	SER	protein dephosphorylation	65/2897	281/18723	4.44e-04	6.51e-03	65
GO:00163111	Colorectum	SER	dephosphorylation	86/2897	417/18723	2.73e-03	2.46e-02	86
GO:0010563111	Esophagus	ESCC	negative regulation of phosphorus metabolic process	274/8552	442/18723	2.32e-12	9.41e-11	274
GO:0045936111	Esophagus	ESCC	negative regulation of phosphate metabolic process	273/8552	441/18723	3.18e-12	1.25e-10	273

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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

PTPRH

SNV

Missense_Mutation

c.2158G>C

p.Gly720Arg

p.G720R

Q9HD43

protein_coding

deleterious(0.04)

probably_damaging(0.909)

TCGA-A1-A0SQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

PTPRH

SNV

Missense_Mutation

novel

c.2322N>G

p.Phe774Leu

p.F774L

Q9HD43

protein_coding

tolerated(0.12)

benign(0.105)

TCGA-AC-A3W6-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

PTPRH

SNV

Missense_Mutation

c.824N>T

p.Cys275Phe

p.C275F

Q9HD43

protein_coding

tolerated(1)

benign(0.001)

TCGA-AO-A12D-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

PTPRH

SNV

Missense_Mutation

novel

c.1672N>C

p.Thr558Pro

p.T558P

Q9HD43

protein_coding

tolerated(0.09)

benign(0.106)

TCGA-B6-A1KI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PTPRH

SNV

Missense_Mutation

rs749839076

c.530N>A

p.Gly177Glu

p.G177E

Q9HD43

protein_coding

tolerated(0.12)

probably_damaging(0.954)

TCGA-E2-A159-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

PTPRH

SNV

Missense_Mutation

c.1772C>G

p.Pro591Arg

p.P591R

Q9HD43

protein_coding

deleterious(0.04)

possibly_damaging(0.461)

TCGA-E9-A1NE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

PTPRH

SNV

Missense_Mutation

rs374566236

c.2416N>A

p.Ala806Thr

p.A806T

Q9HD43

protein_coding

tolerated(0.1)

possibly_damaging(0.79)

TCGA-EW-A1OX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

PTPRH

insertion

In_Frame_Ins

novel

c.1802_1803insATCTGCATATAACAGCCG

p.Gln601_Trp602insSerAlaTyrAsnSerArg

p.Q601_W602insSAYNSR

Q9HD43

protein_coding

TCGA-A2-A0EV-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PTPRH

insertion

Nonsense_Mutation

novel

c.551_552insGTGCAGTCTCTCAGCTCCATCCTAGCCCTGCTGAGTGAGAACCTGC

p.Tyr184Ter

p.Y184*

Q9HD43

protein_coding

TCGA-BH-A0BM-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

PTPRH

SNV

Missense_Mutation

novel

c.1639N>A

p.Ala547Thr

p.A547T

Q9HD43

protein_coding

tolerated(0.05)

possibly_damaging(0.477)

TCGA-2W-A8YY-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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