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: ARHGEF1

Gene summary for ARHGEF1

Gene summary.

Gene information	Species	Human
	Gene symbol	ARHGEF1
	Gene ID	9138
	Gene name	Rho guanine nucleotide exchange factor 1
	Gene Alias	GEF1
	Cytomap	19q13.2
	Gene Type	protein-coding
	GO ID	GO:0007154
	UniProtAcc	A0A024R0R1

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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
9138	ARHGEF1	LZE2T	Human	Esophagus	ESCC	2.88e-04	5.07e-01	0.082
9138	ARHGEF1	LZE4T	Human	Esophagus	ESCC	5.87e-07	2.35e-01	0.0811
9138	ARHGEF1	LZE7T	Human	Esophagus	ESCC	1.58e-17	6.18e-01	0.0667
9138	ARHGEF1	LZE22T	Human	Esophagus	ESCC	8.54e-07	4.11e-01	0.068
9138	ARHGEF1	LZE24T	Human	Esophagus	ESCC	1.17e-14	4.52e-01	0.0596
9138	ARHGEF1	LZE21T	Human	Esophagus	ESCC	2.11e-02	2.67e-01	0.0655
9138	ARHGEF1	LZE6T	Human	Esophagus	ESCC	3.72e-15	5.36e-01	0.0845
9138	ARHGEF1	P1T-E	Human	Esophagus	ESCC	5.82e-08	3.10e-01	0.0875
9138	ARHGEF1	P2T-E	Human	Esophagus	ESCC	1.80e-19	2.94e-01	0.1177
9138	ARHGEF1	P4T-E	Human	Esophagus	ESCC	1.02e-10	1.61e-01	0.1323
9138	ARHGEF1	P5T-E	Human	Esophagus	ESCC	1.42e-11	1.73e-01	0.1327
9138	ARHGEF1	P8T-E	Human	Esophagus	ESCC	8.74e-50	8.33e-01	0.0889
9138	ARHGEF1	P9T-E	Human	Esophagus	ESCC	9.37e-07	1.34e-01	0.1131
9138	ARHGEF1	P10T-E	Human	Esophagus	ESCC	3.42e-23	4.25e-01	0.116
9138	ARHGEF1	P11T-E	Human	Esophagus	ESCC	4.07e-22	8.20e-01	0.1426
9138	ARHGEF1	P12T-E	Human	Esophagus	ESCC	6.03e-25	2.95e-01	0.1122
9138	ARHGEF1	P15T-E	Human	Esophagus	ESCC	7.47e-19	4.98e-01	0.1149
9138	ARHGEF1	P16T-E	Human	Esophagus	ESCC	2.10e-21	2.67e-01	0.1153
9138	ARHGEF1	P17T-E	Human	Esophagus	ESCC	2.44e-09	4.41e-01	0.1278
9138	ARHGEF1	P19T-E	Human	Esophagus	ESCC	4.01e-10	6.90e-01	0.1662

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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
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:000701510	Cervix	CC	actin filament organization	109/2311	442/18723	4.92e-13	2.45e-10	109
GO:003297010	Cervix	CC	regulation of actin filament-based process	96/2311	397/18723	4.00e-11	8.54e-09	96
GO:00071639	Cervix	CC	establishment or maintenance of cell polarity	63/2311	218/18723	4.25e-11	8.76e-09	63
GO:190290310	Cervix	CC	regulation of supramolecular fiber organization	92/2311	383/18723	1.49e-10	2.48e-08	92
GO:003295610	Cervix	CC	regulation of actin cytoskeleton organization	86/2311	358/18723	5.90e-10	7.51e-08	86
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:011005310	Cervix	CC	regulation of actin filament organization	67/2311	278/18723	4.01e-08	2.54e-06	67
GO:00300108	Cervix	CC	establishment of cell polarity	42/2311	143/18723	4.30e-08	2.62e-06	42
GO:006157210	Cervix	CC	actin filament bundle organization	44/2311	161/18723	2.08e-07	9.34e-06	44
GO:005101710	Cervix	CC	actin filament bundle assembly	43/2311	157/18723	2.66e-07	1.12e-05	43
GO:190290510	Cervix	CC	positive regulation of supramolecular fiber organization	50/2311	209/18723	2.55e-06	7.54e-05	50
GO:00160498	Cervix	CC	cell growth	92/2311	482/18723	1.16e-05	2.49e-04	92
GO:00072666	Cervix	CC	Rho protein signal transduction	35/2311	137/18723	1.77e-05	3.33e-04	35
GO:005149510	Cervix	CC	positive regulation of cytoskeleton organization	50/2311	226/18723	2.53e-05	4.29e-04	50
GO:003223110	Cervix	CC	regulation of actin filament bundle assembly	28/2311	105/18723	5.19e-05	7.79e-04	28
GO:011002010	Cervix	CC	regulation of actomyosin structure organization	27/2311	100/18723	5.55e-05	8.10e-04	27
GO:00069846	Cervix	CC	ER-nucleus signaling pathway	16/2311	46/18723	7.12e-05	9.90e-04	16
GO:005149210	Cervix	CC	regulation of stress fiber assembly	25/2311	91/18723	7.59e-05	1.04e-03	25
GO:00310329	Cervix	CC	actomyosin structure organization	43/2311	196/18723	1.11e-04	1.40e-03	43

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05130211	Esophagus	ESCC	Pathogenic Escherichia coli infection	142/4205	197/8465	8.21e-11	1.06e-09	5.42e-10	142
hsa0513526	Esophagus	ESCC	Yersinia infection	100/4205	137/8465	1.80e-08	1.59e-07	8.12e-08	100
hsa0520529	Esophagus	ESCC	Proteoglycans in cancer	138/4205	205/8465	1.79e-07	1.40e-06	7.15e-07	138
hsa05417211	Esophagus	ESCC	Lipid and atherosclerosis	143/4205	215/8465	3.30e-07	2.45e-06	1.26e-06	143
hsa05163210	Esophagus	ESCC	Human cytomegalovirus infection	148/4205	225/8465	5.73e-07	4.00e-06	2.05e-06	148
hsa0481028	Esophagus	ESCC	Regulation of actin cytoskeleton	133/4205	229/8465	5.94e-03	1.48e-02	7.56e-03	133
hsa05130310	Esophagus	ESCC	Pathogenic Escherichia coli infection	142/4205	197/8465	8.21e-11	1.06e-09	5.42e-10	142
hsa05135111	Esophagus	ESCC	Yersinia infection	100/4205	137/8465	1.80e-08	1.59e-07	8.12e-08	100
hsa0520537	Esophagus	ESCC	Proteoglycans in cancer	138/4205	205/8465	1.79e-07	1.40e-06	7.15e-07	138
hsa05417310	Esophagus	ESCC	Lipid and atherosclerosis	143/4205	215/8465	3.30e-07	2.45e-06	1.26e-06	143
hsa0516338	Esophagus	ESCC	Human cytomegalovirus infection	148/4205	225/8465	5.73e-07	4.00e-06	2.05e-06	148
hsa04810112	Esophagus	ESCC	Regulation of actin cytoskeleton	133/4205	229/8465	5.94e-03	1.48e-02	7.56e-03	133
hsa0481021	Liver	Cirrhotic	Regulation of actin cytoskeleton	100/2530	229/8465	5.28e-06	5.50e-05	3.39e-05	100
hsa0513022	Liver	Cirrhotic	Pathogenic Escherichia coli infection	88/2530	197/8465	6.48e-06	6.24e-05	3.84e-05	88
hsa0520510	Liver	Cirrhotic	Proteoglycans in cancer	85/2530	205/8465	2.37e-04	1.58e-03	9.75e-04	85
hsa0513522	Liver	Cirrhotic	Yersinia infection	57/2530	137/8465	2.16e-03	9.41e-03	5.80e-03	57
hsa0516312	Liver	Cirrhotic	Human cytomegalovirus infection	87/2530	225/8465	2.67e-03	1.10e-02	6.76e-03	87
hsa0541722	Liver	Cirrhotic	Lipid and atherosclerosis	80/2530	215/8465	1.18e-02	3.81e-02	2.35e-02	80
hsa0481031	Liver	Cirrhotic	Regulation of actin cytoskeleton	100/2530	229/8465	5.28e-06	5.50e-05	3.39e-05	100
hsa0513032	Liver	Cirrhotic	Pathogenic Escherichia coli infection	88/2530	197/8465	6.48e-06	6.24e-05	3.84e-05	88

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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

ARHGEF1

SNV

Missense_Mutation

c.368N>T

p.Ala123Val

p.A123V

Q92888

protein_coding

deleterious(0)

possibly_damaging(0.506)

TCGA-A2-A04Q-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

ARHGEF1

SNV

Missense_Mutation

c.95N>A

p.Gly32Asp

p.G32D

Q92888

protein_coding

deleterious(0.02)

probably_damaging(0.998)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ARHGEF1

SNV

Missense_Mutation

c.151N>C

p.Glu51Gln

p.E51Q

Q92888

protein_coding

deleterious(0.04)

benign(0.003)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ARHGEF1

SNV

Missense_Mutation

c.139N>C

p.Glu47Gln

p.E47Q

Q92888

protein_coding

tolerated(0.06)

possibly_damaging(0.877)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ARHGEF1

SNV

Missense_Mutation

c.298N>T

p.Gly100Cys

p.G100C

Q92888

protein_coding

deleterious(0.04)

benign(0.005)

TCGA-BH-A0WA-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ARHGEF1

SNV

Missense_Mutation

c.2575N>T

p.Asp859Tyr

p.D859Y

Q92888

protein_coding

deleterious(0)

probably_damaging(0.98)

TCGA-BH-A18V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ARHGEF1

SNV

Missense_Mutation

c.994N>T

p.Pro332Ser

p.P332S

Q92888

protein_coding

tolerated(0.35)

possibly_damaging(0.793)

TCGA-D8-A1XJ-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

tamoxiphen

ARHGEF1

deletion

Frame_Shift_Del

novel

c.527delN

p.Leu177SerfsTer4

p.L177Sfs*4

Q92888

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

ARHGEF1

deletion

Frame_Shift_Del

novel

c.1109delN

p.Met370ArgfsTer61

p.M370Rfs*61

Q92888

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

ARHGEF1

SNV

Missense_Mutation

novel

c.842N>A

p.Ser281Asn

p.S281N

Q92888

protein_coding

tolerated(0.38)

benign(0.205)

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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