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: ARHGEF7

Gene summary for ARHGEF7

Gene summary.

Gene information	Species	Human
	Gene symbol	ARHGEF7
	Gene ID	8874
	Gene name	Rho guanine nucleotide exchange factor 7
	Gene Alias	BETA-PIX
	Cytomap	13q34
	Gene Type	protein-coding
	GO ID	GO:0000226
	UniProtAcc	Q14155

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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
8874	ARHGEF7	CCI_2	Human	Cervix	CC	1.15e-02	5.61e-01	0.5249
8874	ARHGEF7	CCI_3	Human	Cervix	CC	3.24e-07	7.19e-01	0.516
8874	ARHGEF7	LZE4T	Human	Esophagus	ESCC	2.89e-08	2.74e-01	0.0811
8874	ARHGEF7	LZE7T	Human	Esophagus	ESCC	6.10e-03	2.71e-01	0.0667
8874	ARHGEF7	LZE8T	Human	Esophagus	ESCC	5.55e-07	1.96e-01	0.067
8874	ARHGEF7	LZE22T	Human	Esophagus	ESCC	7.70e-03	2.55e-01	0.068
8874	ARHGEF7	LZE24T	Human	Esophagus	ESCC	3.91e-11	1.79e-01	0.0596
8874	ARHGEF7	LZE6T	Human	Esophagus	ESCC	3.09e-05	1.40e-01	0.0845
8874	ARHGEF7	P1T-E	Human	Esophagus	ESCC	2.74e-04	2.33e-01	0.0875
8874	ARHGEF7	P2T-E	Human	Esophagus	ESCC	3.83e-21	3.31e-01	0.1177
8874	ARHGEF7	P4T-E	Human	Esophagus	ESCC	5.97e-09	2.66e-01	0.1323
8874	ARHGEF7	P5T-E	Human	Esophagus	ESCC	2.38e-15	1.78e-01	0.1327
8874	ARHGEF7	P8T-E	Human	Esophagus	ESCC	4.56e-21	3.74e-01	0.0889
8874	ARHGEF7	P9T-E	Human	Esophagus	ESCC	9.06e-09	2.28e-01	0.1131
8874	ARHGEF7	P10T-E	Human	Esophagus	ESCC	2.07e-22	2.99e-01	0.116
8874	ARHGEF7	P11T-E	Human	Esophagus	ESCC	1.09e-10	4.82e-01	0.1426
8874	ARHGEF7	P12T-E	Human	Esophagus	ESCC	2.52e-26	4.87e-01	0.1122
8874	ARHGEF7	P15T-E	Human	Esophagus	ESCC	1.44e-15	3.06e-01	0.1149
8874	ARHGEF7	P16T-E	Human	Esophagus	ESCC	3.82e-28	3.76e-01	0.1153
8874	ARHGEF7	P17T-E	Human	Esophagus	ESCC	4.44e-08	2.49e-01	0.1278

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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
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

∗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:001081010	Cervix	CC	regulation of cell-substrate adhesion	69/2311	221/18723	8.57e-14	5.69e-11	69
GO:00315898	Cervix	CC	cell-substrate adhesion	96/2311	363/18723	1.48e-13	8.85e-11	96
GO:002260410	Cervix	CC	regulation of cell morphogenesis	84/2311	309/18723	1.00e-12	4.29e-10	84
GO:00016679	Cervix	CC	ameboidal-type cell migration	110/2311	475/18723	2.66e-11	6.36e-09	110
GO:190290310	Cervix	CC	regulation of supramolecular fiber organization	92/2311	383/18723	1.49e-10	2.48e-08	92
GO:004578510	Cervix	CC	positive regulation of cell adhesion	101/2311	437/18723	1.96e-10	3.08e-08	101
GO:01501159	Cervix	CC	cell-substrate junction organization	37/2311	101/18723	3.20e-10	4.46e-08	37
GO:004325410	Cervix	CC	regulation of protein-containing complex assembly	96/2311	428/18723	2.91e-09	3.05e-07	96
GO:00070448	Cervix	CC	cell-substrate junction assembly	34/2311	95/18723	3.35e-09	3.45e-07	34
GO:00071608	Cervix	CC	cell-matrix adhesion	60/2311	233/18723	1.58e-08	1.23e-06	60
GO:00430877	Cervix	CC	regulation of GTPase activity	79/2311	348/18723	4.21e-08	2.60e-06	79
GO:00975817	Cervix	CC	lamellipodium organization	31/2311	90/18723	4.57e-08	2.76e-06	31
GO:005125810	Cervix	CC	protein polymerization	70/2311	297/18723	5.20e-08	3.11e-06	70
GO:19000249	Cervix	CC	regulation of substrate adhesion-dependent cell spreading	23/2311	57/18723	8.94e-08	5.04e-06	23
GO:005109810	Cervix	CC	regulation of binding	80/2311	363/18723	1.32e-07	6.42e-06	80
GO:00300325	Cervix	CC	lamellipodium assembly	26/2311	72/18723	1.87e-07	8.48e-06	26
GO:003227110	Cervix	CC	regulation of protein polymerization	57/2311	233/18723	2.37e-07	1.03e-05	57
GO:00107699	Cervix	CC	regulation of cell morphogenesis involved in differentiation	31/2311	96/18723	2.43e-07	1.05e-05	31
GO:00343298	Cervix	CC	cell junction assembly	88/2311	420/18723	3.42e-07	1.38e-05	88
GO:00480417	Cervix	CC	focal adhesion assembly	28/2311	87/18723	9.86e-07	3.45e-05	28

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0481016	Cervix	CC	Regulation of actin cytoskeleton	64/1267	229/8465	2.24e-07	2.59e-06	1.53e-06	64
hsa0513516	Cervix	CC	Yersinia infection	39/1267	137/8465	3.27e-05	2.41e-04	1.42e-04	39
hsa0481017	Cervix	CC	Regulation of actin cytoskeleton	64/1267	229/8465	2.24e-07	2.59e-06	1.53e-06	64
hsa0513517	Cervix	CC	Yersinia infection	39/1267	137/8465	3.27e-05	2.41e-04	1.42e-04	39
hsa0513526	Esophagus	ESCC	Yersinia infection	100/4205	137/8465	1.80e-08	1.59e-07	8.12e-08	100
hsa0481028	Esophagus	ESCC	Regulation of actin cytoskeleton	133/4205	229/8465	5.94e-03	1.48e-02	7.56e-03	133
hsa05135111	Esophagus	ESCC	Yersinia infection	100/4205	137/8465	1.80e-08	1.59e-07	8.12e-08	100
hsa04810112	Esophagus	ESCC	Regulation of actin cytoskeleton	133/4205	229/8465	5.94e-03	1.48e-02	7.56e-03	133
hsa0481010	Liver	NAFLD	Regulation of actin cytoskeleton	50/1043	229/8465	3.01e-05	7.59e-04	6.11e-04	50
hsa0513512	Liver	NAFLD	Yersinia infection	33/1043	137/8465	9.44e-05	1.94e-03	1.56e-03	33
hsa0481011	Liver	NAFLD	Regulation of actin cytoskeleton	50/1043	229/8465	3.01e-05	7.59e-04	6.11e-04	50
hsa0513513	Liver	NAFLD	Yersinia infection	33/1043	137/8465	9.44e-05	1.94e-03	1.56e-03	33
hsa0513542	Liver	HCC	Yersinia infection	92/4020	137/8465	2.25e-06	2.19e-05	1.22e-05	92
hsa0481041	Liver	HCC	Regulation of actin cytoskeleton	134/4020	229/8465	4.48e-04	1.94e-03	1.08e-03	134
hsa0513552	Liver	HCC	Yersinia infection	92/4020	137/8465	2.25e-06	2.19e-05	1.22e-05	92
hsa0481051	Liver	HCC	Regulation of actin cytoskeleton	134/4020	229/8465	4.48e-04	1.94e-03	1.08e-03	134
hsa0513520	Oral cavity	OSCC	Yersinia infection	94/3704	137/8465	2.85e-09	3.08e-08	1.57e-08	94
hsa0481026	Oral cavity	OSCC	Regulation of actin cytoskeleton	129/3704	229/8465	7.14e-05	2.74e-04	1.40e-04	129
hsa05135110	Oral cavity	OSCC	Yersinia infection	94/3704	137/8465	2.85e-09	3.08e-08	1.57e-08	94
hsa04810111	Oral cavity	OSCC	Regulation of actin cytoskeleton	129/3704	229/8465	7.14e-05	2.74e-04	1.40e-04	129

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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

ARHGEF7

SNV

Missense_Mutation

rs765860102

c.1483N>A

p.Glu495Lys

p.E495K

Q14155

protein_coding

deleterious(0.01)

possibly_damaging(0.881)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

ARHGEF7

SNV

Missense_Mutation

c.1321T>C

p.Phe441Leu

p.F441L

Q14155

protein_coding

deleterious(0.03)

probably_damaging(1)

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

ARHGEF7

SNV

Missense_Mutation

novel

c.2085G>A

p.Met695Ile

p.M695I

protein_coding

tolerated(0.3)

benign(0.003)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ARHGEF7

SNV

Missense_Mutation

c.1355G>A

p.Arg452Gln

p.R452Q

Q14155

protein_coding

deleterious(0)

benign(0.415)

TCGA-BH-A1EO-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ARHGEF7

SNV

Missense_Mutation

c.1297N>A

p.Asp433Asn

p.D433N

Q14155

protein_coding

deleterious(0.01)

probably_damaging(0.965)

TCGA-GM-A2DF-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxol

ARHGEF7

SNV

Missense_Mutation

c.2060N>T

p.Arg687Leu

p.R687L

Q14155

protein_coding

deleterious(0.03)

probably_damaging(0.999)

TCGA-JL-A3YW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ARHGEF7

insertion

In_Frame_Ins

novel

c.1112_1113insTTATATTTTTGGTTTTCTGTATCATGAACTTTT

p.Ala371_Val372insTyrIlePheGlyPheLeuTyrHisGluLeuLeu

p.A371_V372insYIFGFLYHELL

Q14155

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ARHGEF7

insertion

Frame_Shift_Ins

novel

c.483_484insTTAAAAAAAGAAAATCACTTATCTAAAGTTATGGATGACA

p.His163LysfsTer33

p.H163Kfs*33

Q14155

protein_coding

TCGA-BH-A0BD-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

ARHGEF7

SNV

Missense_Mutation

novel

c.1926G>T

p.Glu642Asp

p.E642D

Q14155

protein_coding

deleterious(0.02)

probably_damaging(0.997)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ARHGEF7

SNV

Missense_Mutation

c.2230G>A

p.Val744Ile

p.V744I

Q14155

protein_coding

tolerated(0.07)

benign(0.088)

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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