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: ARHGAP32

Gene summary for ARHGAP32

Gene summary.

Gene information	Species	Human
	Gene symbol	ARHGAP32
	Gene ID	9743
	Gene name	Rho GTPase activating protein 32
	Gene Alias	GC-GAP
	Cytomap	11q24.3
	Gene Type	protein-coding
	GO ID	GO:0007154
	UniProtAcc	A7KAX9

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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
9743	ARHGAP32	A002-C-114	Human	Colorectum	FAP	1.38e-23	-4.22e-01	-0.1561
9743	ARHGAP32	A015-C-104	Human	Colorectum	FAP	2.36e-47	-5.97e-01	-0.1899
9743	ARHGAP32	A001-C-014	Human	Colorectum	FAP	3.57e-20	-2.57e-01	0.0135
9743	ARHGAP32	A002-C-016	Human	Colorectum	FAP	2.52e-30	-3.96e-01	0.0521
9743	ARHGAP32	A015-C-002	Human	Colorectum	FAP	2.29e-17	-3.64e-01	-0.0763
9743	ARHGAP32	A001-C-203	Human	Colorectum	FAP	8.29e-13	-1.78e-01	-0.0481
9743	ARHGAP32	A002-C-116	Human	Colorectum	FAP	1.68e-54	-5.15e-01	-0.0452
9743	ARHGAP32	A014-C-008	Human	Colorectum	FAP	8.77e-20	-3.94e-01	-0.191
9743	ARHGAP32	A018-E-020	Human	Colorectum	FAP	3.24e-31	-5.42e-01	-0.2034
9743	ARHGAP32	F034	Human	Colorectum	FAP	2.15e-32	-3.39e-01	-0.0665
9743	ARHGAP32	F072B	Human	Colorectum	FAP	3.05e-06	-1.02e-01	0.257
9743	ARHGAP32	CRC-1-8810	Human	Colorectum	CRC	5.06e-03	-2.10e-01	0.6257
9743	ARHGAP32	CRC-3-11773	Human	Colorectum	CRC	2.34e-09	-1.52e-01	0.2564
9743	ARHGAP32	AEH-subject1	Human	Endometrium	AEH	4.23e-15	4.76e-01	-0.3059
9743	ARHGAP32	AEH-subject2	Human	Endometrium	AEH	1.26e-09	4.46e-01	-0.2525
9743	ARHGAP32	AEH-subject3	Human	Endometrium	AEH	6.43e-04	2.70e-01	-0.2576
9743	ARHGAP32	AEH-subject4	Human	Endometrium	AEH	2.00e-07	4.13e-01	-0.2657
9743	ARHGAP32	AEH-subject5	Human	Endometrium	AEH	1.90e-40	8.96e-01	-0.2953
9743	ARHGAP32	EEC-subject1	Human	Endometrium	EEC	7.85e-16	6.00e-01	-0.2682
9743	ARHGAP32	EEC-subject2	Human	Endometrium	EEC	1.34e-09	4.09e-01	-0.2607

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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
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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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
Prostate		BPH: Benign Prostatic Hyperplasia
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ

∗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:00510566	Cervix	CC	regulation of small GTPase mediated signal transduction	75/2311	302/18723	1.54e-09	1.74e-07	75
GO:0051056	Colorectum	AD	regulation of small GTPase mediated signal transduction	94/3918	302/18723	1.81e-05	3.76e-04	94
GO:00510561	Colorectum	MSS	regulation of small GTPase mediated signal transduction	82/3467	302/18723	1.31e-04	1.99e-03	82
GO:00510562	Colorectum	FAP	regulation of small GTPase mediated signal transduction	78/2622	302/18723	3.25e-08	2.85e-06	78
GO:00510563	Colorectum	CRC	regulation of small GTPase mediated signal transduction	69/2078	302/18723	3.34e-09	9.08e-07	69
GO:00510567	Endometrium	AEH	regulation of small GTPase mediated signal transduction	59/2100	302/18723	1.43e-05	3.03e-04	59
GO:005105612	Endometrium	EEC	regulation of small GTPase mediated signal transduction	61/2168	302/18723	9.42e-06	2.08e-04	61
GO:005105610	Esophagus	ESCC	regulation of small GTPase mediated signal transduction	157/8552	302/18723	1.55e-02	4.98e-02	157
GO:00510565	Lung	IAC	regulation of small GTPase mediated signal transduction	70/2061	302/18723	9.44e-10	1.87e-07	70
GO:005105611	Lung	AIS	regulation of small GTPase mediated signal transduction	66/1849	302/18723	4.26e-10	9.53e-08	66
GO:005105621	Lung	MIAC	regulation of small GTPase mediated signal transduction	35/967	302/18723	6.81e-06	6.35e-04	35
GO:00510569	Oral cavity	EOLP	regulation of small GTPase mediated signal transduction	51/2218	302/18723	5.67e-03	2.92e-02	51
GO:005105614	Oral cavity	NEOLP	regulation of small GTPase mediated signal transduction	49/2005	302/18723	2.04e-03	1.36e-02	49
GO:00510568	Prostate	BPH	regulation of small GTPase mediated signal transduction	78/3107	302/18723	2.69e-05	3.16e-04	78
GO:005105613	Prostate	Tumor	regulation of small GTPase mediated signal transduction	80/3246	302/18723	3.96e-05	4.57e-04	80
GO:005105615	Skin	AK	regulation of small GTPase mediated signal transduction	48/1910	302/18723	1.28e-03	9.69e-03	48
GO:005105616	Skin	SCCIS	regulation of small GTPase mediated signal transduction	33/919	302/18723	1.49e-05	4.86e-04	33

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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

ARHGAP32

SNV

Missense_Mutation

rs149060649

c.2105N>A

p.Arg702His

p.R702H

A7KAX9

protein_coding

deleterious(0)

possibly_damaging(0.657)

TCGA-AN-A0FF-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ARHGAP32

SNV

Missense_Mutation

c.2382N>G

p.Asp794Glu

p.D794E

A7KAX9

protein_coding

deleterious(0)

possibly_damaging(0.866)

TCGA-AO-A03T-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

ARHGAP32

SNV

Missense_Mutation

c.2207N>G

p.Ser736Cys

p.S736C

A7KAX9

protein_coding

deleterious(0.01)

benign(0.287)

TCGA-BH-A0HP-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

doxorubicin

ARHGAP32

SNV

Missense_Mutation

rs749143928

c.3131N>T

p.Ala1044Val

p.A1044V

A7KAX9

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.996)

TCGA-D8-A1Y1-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

tamoxiphen

ARHGAP32

SNV

Missense_Mutation

novel

c.1817N>T

p.Arg606Leu

p.R606L

A7KAX9

protein_coding

deleterious(0)

probably_damaging(0.963)

TCGA-LL-A6FP-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

ARHGAP32

SNV

Missense_Mutation

novel

c.3792N>A

p.Met1264Ile

p.M1264I

A7KAX9

protein_coding

deleterious_low_confidence(0.05)

benign(0)

TCGA-PE-A5DD-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

ARHGAP32

SNV

Missense_Mutation

rs746604429

c.4765N>T

p.Pro1589Ser

p.P1589S

A7KAX9

protein_coding

tolerated(0.08)

possibly_damaging(0.573)

TCGA-S3-AA15-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

ARHGAP32

insertion

Nonsense_Mutation

novel

c.2785_2786insTCCTGTGTGCCATCTGTGCCTTTTAAGAGAGAAATTTGT

p.Thr929delinsIleLeuCysAlaIleCysAlaPheTerGluArgAsnLeuSer

p.T929delinsILCAICAF*ERNLS

A7KAX9

protein_coding

TCGA-A2-A0CM-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

ARHGAP32

insertion

Frame_Shift_Ins

novel

c.3911_3912insACACAACAAT

p.Pro1305HisfsTer33

p.P1305Hfs*33

A7KAX9

protein_coding

TCGA-A7-A0CE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

ARHGAP32

insertion

Nonsense_Mutation

novel

c.3910_3911insTTTGAGTCA

p.Arg1304delinsLeuTerValSer

p.R1304delinsL*VS

A7KAX9

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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