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: ARHGAP21

Gene summary for ARHGAP21

Gene summary.

Gene information	Species	Human
	Gene symbol	ARHGAP21
	Gene ID	57584
	Gene name	Rho GTPase activating protein 21
	Gene Alias	ARHGAP10
	Cytomap	10p12.1
	Gene Type	protein-coding
	GO ID	GO:0006810
	UniProtAcc	Q5T5U3

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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
57584	ARHGAP21	CCI_1	Human	Cervix	CC	6.74e-05	1.22e+00	0.528
57584	ARHGAP21	CCI_2	Human	Cervix	CC	5.01e-06	8.67e-01	0.5249
57584	ARHGAP21	CCI_3	Human	Cervix	CC	8.83e-22	1.26e+00	0.516
57584	ARHGAP21	Tumor	Human	Cervix	CC	3.37e-06	2.76e-01	0.1241
57584	ARHGAP21	sample1	Human	Cervix	CC	4.74e-13	6.84e-01	0.0959
57584	ARHGAP21	sample3	Human	Cervix	CC	1.45e-16	4.31e-01	0.1387
57584	ARHGAP21	T1	Human	Cervix	CC	5.11e-24	6.87e-01	0.0918
57584	ARHGAP21	T3	Human	Cervix	CC	1.64e-19	4.16e-01	0.1389
57584	ARHGAP21	HTA11_3410_2000001011	Human	Colorectum	AD	3.92e-06	-4.74e-01	0.0155
57584	ARHGAP21	HTA11_347_2000001011	Human	Colorectum	AD	9.86e-05	3.81e-01	-0.1954
57584	ARHGAP21	HTA11_7696_3000711011	Human	Colorectum	AD	1.48e-02	-3.29e-01	0.0674
57584	ARHGAP21	HTA11_7469_2000001011	Human	Colorectum	AD	2.86e-02	1.29e-01	-0.0124
57584	ARHGAP21	HTA11_99999973899_84307	Human	Colorectum	MSS	7.56e-03	-5.76e-01	0.2585
57584	ARHGAP21	HTA11_99999974143_84620	Human	Colorectum	MSS	3.73e-25	-7.00e-01	0.3005
57584	ARHGAP21	A002-C-010	Human	Colorectum	FAP	7.40e-03	-1.21e-01	0.242
57584	ARHGAP21	A001-C-207	Human	Colorectum	FAP	2.08e-04	-2.04e-01	0.1278
57584	ARHGAP21	A015-C-203	Human	Colorectum	FAP	3.14e-28	-2.71e-01	-0.1294
57584	ARHGAP21	A015-C-204	Human	Colorectum	FAP	6.52e-06	-1.90e-01	-0.0228
57584	ARHGAP21	A014-C-040	Human	Colorectum	FAP	2.02e-07	-4.24e-01	-0.1184
57584	ARHGAP21	A002-C-201	Human	Colorectum	FAP	1.86e-14	-2.56e-01	0.0324

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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
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
Prostate		BPH: Benign Prostatic Hyperplasia
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:00510566	Cervix	CC	regulation of small GTPase mediated signal transduction	75/2311	302/18723	1.54e-09	1.74e-07	75
GO:00512359	Cervix	CC	maintenance of location	78/2311	327/18723	5.18e-09	4.92e-07	78
GO:005165110	Cervix	CC	maintenance of location in cell	55/2311	214/18723	6.63e-08	3.85e-06	55
GO:00516567	Cervix	CC	establishment of organelle localization	76/2311	390/18723	3.17e-05	5.21e-04	76
GO:00307057	Cervix	CC	cytoskeleton-dependent intracellular transport	40/2311	195/18723	7.92e-04	6.99e-03	40
GO:00070304	Cervix	CC	Golgi organization	32/2311	157/18723	2.78e-03	1.87e-02	32
GO:00516572	Cervix	CC	maintenance of organelle location	5/2311	11/18723	6.92e-03	3.74e-02	5
GO:0051656	Colorectum	AD	establishment of organelle localization	131/3918	390/18723	3.00e-09	2.06e-07	131
GO:0051056	Colorectum	AD	regulation of small GTPase mediated signal transduction	94/3918	302/18723	1.81e-05	3.76e-04	94
GO:0030705	Colorectum	AD	cytoskeleton-dependent intracellular transport	60/3918	195/18723	7.56e-04	7.59e-03	60
GO:0051651	Colorectum	AD	maintenance of location in cell	61/3918	214/18723	5.02e-03	3.37e-02	61
GO:0072384	Colorectum	AD	organelle transport along microtubule	28/3918	85/18723	6.55e-03	4.07e-02	28
GO:00516562	Colorectum	MSS	establishment of organelle localization	115/3467	390/18723	7.30e-08	3.67e-06	115
GO:00510561	Colorectum	MSS	regulation of small GTPase mediated signal transduction	82/3467	302/18723	1.31e-04	1.99e-03	82
GO:00516512	Colorectum	MSS	maintenance of location in cell	57/3467	214/18723	2.07e-03	1.76e-02	57
GO:00307052	Colorectum	MSS	cytoskeleton-dependent intracellular transport	52/3467	195/18723	3.07e-03	2.34e-02	52
GO:0051645	Colorectum	MSS	Golgi localization	7/3467	14/18723	7.51e-03	4.72e-02	7
GO:00516563	Colorectum	FAP	establishment of organelle localization	97/2622	390/18723	5.91e-09	9.48e-07	97
GO:00510562	Colorectum	FAP	regulation of small GTPase mediated signal transduction	78/2622	302/18723	3.25e-08	2.85e-06	78
GO:00307053	Colorectum	FAP	cytoskeleton-dependent intracellular transport	47/2622	195/18723	1.06e-04	1.76e-03	47

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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

ARHGAP21

SNV

Missense_Mutation

c.332G>T

p.Gly111Val

p.G111V

Q5T5U3

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-A2-A0ST-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

ARHGAP21

SNV

Missense_Mutation

c.4387N>A

p.Glu1463Lys

p.E1463K

Q5T5U3

protein_coding

tolerated(0.06)

benign(0.018)

TCGA-A8-A095-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

ARHGAP21

SNV

Missense_Mutation

novel

c.1106N>T

p.Pro369Leu

p.P369L

Q5T5U3

protein_coding

deleterious(0.04)

possibly_damaging(0.836)

TCGA-A8-A09D-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

ARHGAP21

SNV

Missense_Mutation

c.4444N>C

p.Asp1482His

p.D1482H

Q5T5U3

protein_coding

tolerated(0.09)

benign(0.059)

TCGA-A8-A0A9-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

ARHGAP21

SNV

Missense_Mutation

novel

c.2366N>T

p.Arg789Ile

p.R789I

Q5T5U3

protein_coding

deleterious(0.01)

probably_damaging(0.999)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ARHGAP21

SNV

Missense_Mutation

c.2341N>T

p.Val781Phe

p.V781F

Q5T5U3

protein_coding

tolerated(0.11)

probably_damaging(0.999)

TCGA-AR-A0TT-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

ARHGAP21

SNV

Missense_Mutation

novel

c.3446N>C

p.Leu1149Pro

p.L1149P

Q5T5U3

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AR-A5QQ-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

carboplatin

ARHGAP21

SNV

Missense_Mutation

c.4558C>T

p.Arg1520Cys

p.R1520C

Q5T5U3

protein_coding

deleterious(0)

probably_damaging(0.927)

TCGA-B6-A0RE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ARHGAP21

SNV

Missense_Mutation

c.3338N>G

p.Asp1113Gly

p.D1113G

Q5T5U3

protein_coding

deleterious(0)

possibly_damaging(0.756)

TCGA-B6-A0RL-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ARHGAP21

SNV

Missense_Mutation

c.2932N>A

p.Glu978Lys

p.E978K

Q5T5U3

protein_coding

deleterious(0)

possibly_damaging(0.74)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

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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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