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: ARHGAP24

Gene summary for ARHGAP24

Gene summary.

Gene information	Species	Human
	Gene symbol	ARHGAP24
	Gene ID	83478
	Gene name	Rho GTPase activating protein 24
	Gene Alias	FILGAP
	Cytomap	4q21.23-q21.3
	Gene Type	protein-coding
	GO ID	GO:0001525
	UniProtAcc	Q8N264

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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
83478	ARHGAP24	CA_HPV_3	Human	Cervix	CC	1.01e-07	2.42e-01	0.0414
83478	ARHGAP24	CCI_1	Human	Cervix	CC	6.50e-23	1.41e+00	0.528
83478	ARHGAP24	CCI_3	Human	Cervix	CC	1.02e-12	6.60e-01	0.516
83478	ARHGAP24	LZE7T	Human	Esophagus	ESCC	8.33e-05	2.57e-01	0.0667
83478	ARHGAP24	LZE8T	Human	Esophagus	ESCC	2.23e-08	3.30e-01	0.067
83478	ARHGAP24	P1T-E	Human	Esophagus	ESCC	2.74e-03	1.58e-01	0.0875
83478	ARHGAP24	P2T-E	Human	Esophagus	ESCC	1.07e-31	5.87e-01	0.1177
83478	ARHGAP24	P4T-E	Human	Esophagus	ESCC	1.01e-13	3.66e-01	0.1323
83478	ARHGAP24	P8T-E	Human	Esophagus	ESCC	2.29e-04	1.15e-01	0.0889
83478	ARHGAP24	P9T-E	Human	Esophagus	ESCC	1.02e-10	3.06e-01	0.1131
83478	ARHGAP24	P10T-E	Human	Esophagus	ESCC	3.65e-13	2.22e-01	0.116
83478	ARHGAP24	P11T-E	Human	Esophagus	ESCC	1.79e-04	2.95e-01	0.1426
83478	ARHGAP24	P12T-E	Human	Esophagus	ESCC	1.55e-29	5.66e-01	0.1122
83478	ARHGAP24	P15T-E	Human	Esophagus	ESCC	1.22e-15	3.84e-01	0.1149
83478	ARHGAP24	P16T-E	Human	Esophagus	ESCC	1.92e-06	1.12e-01	0.1153
83478	ARHGAP24	P19T-E	Human	Esophagus	ESCC	2.84e-04	6.22e-01	0.1662
83478	ARHGAP24	P20T-E	Human	Esophagus	ESCC	4.61e-13	3.04e-01	0.1124
83478	ARHGAP24	P22T-E	Human	Esophagus	ESCC	8.81e-06	1.63e-01	0.1236
83478	ARHGAP24	P23T-E	Human	Esophagus	ESCC	8.83e-18	4.35e-01	0.108
83478	ARHGAP24	P26T-E	Human	Esophagus	ESCC	6.01e-41	8.11e-01	0.1276

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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
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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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:004206010	Cervix	CC	wound healing	109/2311	422/18723	1.84e-14	1.57e-11	109
GO:00510566	Cervix	CC	regulation of small GTPase mediated signal transduction	75/2311	302/18723	1.54e-09	1.74e-07	75
GO:00072656	Cervix	CC	Ras protein signal transduction	79/2311	337/18723	9.49e-09	7.77e-07	79
GO:00430877	Cervix	CC	regulation of GTPase activity	79/2311	348/18723	4.21e-08	2.60e-06	79
GO:00443193	Cervix	CC	wound healing, spreading of cells	17/2311	34/18723	9.86e-08	5.25e-06	17
GO:00905053	Cervix	CC	epiboly involved in wound healing	17/2311	34/18723	9.86e-08	5.25e-06	17
GO:00905043	Cervix	CC	epiboly	17/2311	35/18723	1.70e-07	7.93e-06	17
GO:00020111	Cervix	CC	morphogenesis of an epithelial sheet	21/2311	57/18723	1.91e-06	5.97e-05	21
GO:00465785	Cervix	CC	regulation of Ras protein signal transduction	44/2311	189/18723	2.05e-05	3.73e-04	44
GO:00435476	Cervix	CC	positive regulation of GTPase activity	53/2311	255/18723	8.72e-05	1.16e-03	53
GO:00313456	Cervix	CC	negative regulation of cell projection organization	39/2311	186/18723	5.86e-04	5.57e-03	39
GO:0035313	Cervix	CC	wound healing, spreading of epidermal cells	8/2311	19/18723	1.14e-03	9.34e-03	8
GO:01200328	Cervix	CC	regulation of plasma membrane bounded cell projection assembly	38/2311	186/18723	1.14e-03	9.35e-03	38
GO:00604917	Cervix	CC	regulation of cell projection assembly	38/2311	188/18723	1.40e-03	1.10e-02	38
GO:00510585	Cervix	CC	negative regulation of small GTPase mediated signal transduction	15/2311	56/18723	2.60e-03	1.80e-02	15
GO:00166015	Cervix	CC	Rac protein signal transduction	12/2311	42/18723	3.82e-03	2.41e-02	12
GO:00465804	Cervix	CC	negative regulation of Ras protein signal transduction	13/2311	49/18723	5.34e-03	3.10e-02	13
GO:000726510	Esophagus	ESCC	Ras protein signal transduction	201/8552	337/18723	1.44e-07	2.30e-06	201
GO:004206027	Esophagus	ESCC	wound healing	243/8552	422/18723	4.62e-07	6.25e-06	243
GO:00166019	Esophagus	ESCC	Rac protein signal transduction	33/8552	42/18723	1.35e-05	1.23e-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

ARHGAP24

SNV

Missense_Mutation

novel

c.2090N>C

p.Ile697Thr

p.I697T

Q8N264

protein_coding

deleterious(0)

benign(0.039)

TCGA-AC-A2FE-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

ARHGAP24

SNV

Missense_Mutation

c.1666N>C

p.Ser556Pro

p.S556P

Q8N264

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-AN-A0AT-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ARHGAP24

SNV

Missense_Mutation

rs553105622

c.869C>T

p.Thr290Met

p.T290M

Q8N264

protein_coding

deleterious(0)

probably_damaging(0.916)

TCGA-BH-A0HB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

docetaxel

ARHGAP24

SNV

Missense_Mutation

c.2070G>C

p.Glu690Asp

p.E690D

Q8N264

protein_coding

deleterious(0.02)

probably_damaging(0.978)

TCGA-D8-A1JA-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

ARHGAP24

SNV

Missense_Mutation

c.298N>T

p.His100Tyr

p.H100Y

Q8N264

protein_coding

deleterious(0.04)

benign(0.026)

TCGA-D8-A1JL-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ARHGAP24

SNV

Missense_Mutation

rs768287557

c.424C>T

p.Arg142Cys

p.R142C

Q8N264

protein_coding

deleterious(0.03)

possibly_damaging(0.84)

TCGA-LL-A8F5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

ARHGAP24

SNV

Missense_Mutation

c.1816G>T

p.Asp606Tyr

p.D606Y

Q8N264

protein_coding

deleterious(0)

possibly_damaging(0.656)

TCGA-LL-A8F5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

ARHGAP24

insertion

Frame_Shift_Ins

novel

c.1419_1420insTCCATTT

p.Thr474SerfsTer43

p.T474Sfs*43

Q8N264

protein_coding

TCGA-A8-A09E-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozole

ARHGAP24

insertion

Frame_Shift_Ins

novel

c.1421_1422insAGATGCCACTAAAATATCTT

p.His475AspfsTer20

p.H475Dfs*20

Q8N264

protein_coding

TCGA-A8-A09E-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozole

ARHGAP24

insertion

Frame_Shift_Ins

novel

c.1455_1456insAATATAAATAA

p.Ile486AsnfsTer6

p.I486Nfs*6

Q8N264

protein_coding

TCGA-AN-A04A-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

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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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