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: VAV2

Gene summary for VAV2

Gene summary.

Gene information	Species	Human
	Gene symbol	VAV2
	Gene ID	7410
	Gene name	vav guanine nucleotide exchange factor 2
	Gene Alias	VAV-2
	Cytomap	9q34.2
	Gene Type	protein-coding
	GO ID	GO:0001525
	UniProtAcc	P52735

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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
7410	VAV2	CCI_1	Human	Cervix	CC	3.21e-02	4.02e-01	0.528
7410	VAV2	CCI_2	Human	Cervix	CC	3.61e-12	1.19e+00	0.5249
7410	VAV2	CCI_3	Human	Cervix	CC	3.64e-14	1.03e+00	0.516
7410	VAV2	NAFLD1	Human	Liver	NAFLD	1.80e-07	6.51e-01	-0.04
7410	VAV2	S41	Human	Liver	Cirrhotic	2.36e-02	5.43e-01	-0.0343
7410	VAV2	S43	Human	Liver	Cirrhotic	1.02e-02	-5.61e-02	-0.0187
7410	VAV2	HCC1_Meng	Human	Liver	HCC	4.85e-20	-1.10e-01	0.0246
7410	VAV2	HCC2_Meng	Human	Liver	HCC	8.02e-17	3.63e-02	0.0107
7410	VAV2	Pt13.a	Human	Liver	HCC	3.02e-02	-1.23e-01	0.021
7410	VAV2	S028	Human	Liver	HCC	1.77e-02	3.26e-01	0.2503
7410	VAV2	S029	Human	Liver	HCC	1.74e-04	4.53e-01	0.2581
7410	VAV2	C04	Human	Oral cavity	OSCC	4.83e-12	4.60e-01	0.2633
7410	VAV2	C21	Human	Oral cavity	OSCC	3.71e-22	6.31e-01	0.2678
7410	VAV2	C30	Human	Oral cavity	OSCC	1.41e-55	1.93e+00	0.3055
7410	VAV2	C43	Human	Oral cavity	OSCC	4.27e-10	2.10e-01	0.1704
7410	VAV2	C46	Human	Oral cavity	OSCC	1.91e-08	1.84e-01	0.1673
7410	VAV2	C51	Human	Oral cavity	OSCC	1.14e-25	8.65e-01	0.2674
7410	VAV2	C06	Human	Oral cavity	OSCC	3.43e-10	1.12e+00	0.2699
7410	VAV2	C09	Human	Oral cavity	OSCC	7.57e-10	3.02e-01	0.1431
7410	VAV2	LN46	Human	Oral cavity	OSCC	1.71e-03	2.12e-01	0.1666

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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
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: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:003367410	Cervix	CC	positive regulation of kinase activity	101/2311	467/18723	8.66e-09	7.22e-07	101
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:00027644	Cervix	CC	immune response-regulating signaling pathway	97/2311	468/18723	1.49e-07	7.07e-06	97
GO:00300325	Cervix	CC	lamellipodium assembly	26/2311	72/18723	1.87e-07	8.48e-06	26
GO:005087810	Cervix	CC	regulation of body fluid levels	78/2311	379/18723	3.20e-06	8.77e-05	78
GO:00380933	Cervix	CC	Fc receptor signaling pathway	19/2311	50/18723	3.42e-06	9.17e-05	19
GO:00325359	Cervix	CC	regulation of cellular component size	76/2311	383/18723	1.66e-05	3.21e-04	76
GO:0038095	Cervix	CC	Fc-epsilon receptor signaling pathway	11/2311	24/18723	5.28e-05	7.88e-04	11
GO:00022533	Cervix	CC	activation of immune response	72/2311	375/18723	8.26e-05	1.11e-03	72
GO:0038094	Cervix	CC	Fc-gamma receptor signaling pathway	11/2311	28/18723	2.84e-04	3.07e-03	11
GO:0002431	Cervix	CC	Fc receptor mediated stimulatory signaling pathway	12/2311	33/18723	3.53e-04	3.68e-03	12
GO:00508176	Cervix	CC	coagulation	45/2311	222/18723	5.08e-04	4.94e-03	45
GO:00075966	Cervix	CC	blood coagulation	44/2311	217/18723	5.78e-04	5.52e-03	44
GO:0002768	Cervix	CC	immune response-regulating cell surface receptor signaling pathway	59/2311	315/18723	6.64e-04	6.11e-03	59
GO:00301682	Cervix	CC	platelet activation	28/2311	123/18723	8.92e-04	7.71e-03	28
GO:00024331	Cervix	CC	immune response-regulating cell surface receptor signaling pathway involved in phagocytosis	10/2311	27/18723	9.25e-04	7.84e-03	10
GO:00380961	Cervix	CC	Fc-gamma receptor signaling pathway involved in phagocytosis	10/2311	27/18723	9.25e-04	7.84e-03	10

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0541720	Cervix	CC	Lipid and atherosclerosis	65/1267	215/8465	6.47e-09	1.10e-07	6.52e-08	65
hsa0520516	Cervix	CC	Proteoglycans in cancer	60/1267	205/8465	9.13e-08	1.18e-06	7.00e-07	60
hsa0451010	Cervix	CC	Focal adhesion	59/1267	203/8465	1.53e-07	1.84e-06	1.09e-06	59
hsa0481016	Cervix	CC	Regulation of actin cytoskeleton	64/1267	229/8465	2.24e-07	2.59e-06	1.53e-06	64
hsa0467020	Cervix	CC	Leukocyte transendothelial migration	36/1267	114/8465	5.22e-06	4.83e-05	2.86e-05	36
hsa0401512	Cervix	CC	Rap1 signaling pathway	56/1267	210/8465	6.23e-06	5.61e-05	3.32e-05	56
hsa0466612	Cervix	CC	Fc gamma R-mediated phagocytosis	31/1267	97/8465	1.78e-05	1.42e-04	8.40e-05	31
hsa0513516	Cervix	CC	Yersinia infection	39/1267	137/8465	3.27e-05	2.41e-04	1.42e-04	39
hsa04664	Cervix	CC	Fc epsilon RI signaling pathway	22/1267	68/8465	2.35e-04	1.31e-03	7.77e-04	22
hsa04062	Cervix	CC	Chemokine signaling pathway	43/1267	192/8465	3.60e-03	1.34e-02	7.91e-03	43
hsa046604	Cervix	CC	T cell receptor signaling pathway	25/1267	104/8465	9.52e-03	2.94e-02	1.74e-02	25
hsa05417110	Cervix	CC	Lipid and atherosclerosis	65/1267	215/8465	6.47e-09	1.10e-07	6.52e-08	65
hsa0520517	Cervix	CC	Proteoglycans in cancer	60/1267	205/8465	9.13e-08	1.18e-06	7.00e-07	60
hsa0451014	Cervix	CC	Focal adhesion	59/1267	203/8465	1.53e-07	1.84e-06	1.09e-06	59
hsa0481017	Cervix	CC	Regulation of actin cytoskeleton	64/1267	229/8465	2.24e-07	2.59e-06	1.53e-06	64
hsa04670110	Cervix	CC	Leukocyte transendothelial migration	36/1267	114/8465	5.22e-06	4.83e-05	2.86e-05	36
hsa0401513	Cervix	CC	Rap1 signaling pathway	56/1267	210/8465	6.23e-06	5.61e-05	3.32e-05	56
hsa0466613	Cervix	CC	Fc gamma R-mediated phagocytosis	31/1267	97/8465	1.78e-05	1.42e-04	8.40e-05	31
hsa0513517	Cervix	CC	Yersinia infection	39/1267	137/8465	3.27e-05	2.41e-04	1.42e-04	39
hsa046641	Cervix	CC	Fc epsilon RI signaling pathway	22/1267	68/8465	2.35e-04	1.31e-03	7.77e-04	22

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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

VAV2

SNV

Missense_Mutation

c.2278G>A

p.Asp760Asn

p.D760N

P52735

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

VAV2

SNV

Missense_Mutation

novel

c.1603A>C

p.Thr535Pro

p.T535P

P52735

protein_coding

deleterious(0.03)

probably_damaging(0.999)

TCGA-D8-A1JD-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

VAV2

SNV

Missense_Mutation

c.2366A>G

p.Asn789Ser

p.N789S

P52735

protein_coding

tolerated(0.36)

probably_damaging(0.956)

TCGA-E2-A15J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

docetaxel

VAV2

insertion

Frame_Shift_Ins

novel

c.2153_2154insTGGCTCTCTGTCACTTGGAGATCCTG

p.Lys718AsnfsTer44

p.K718Nfs*44

P52735

protein_coding

TCGA-BH-A0HK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

VAV2

deletion

Frame_Shift_Del

novel

c.2440delA

p.Thr814ArgfsTer19

p.T814Rfs*19

P52735

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

VAV2

deletion

Frame_Shift_Del

novel

c.1383delC

p.Met462Ter

p.M462*

P52735

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

VAV2

insertion

Frame_Shift_Ins

novel

c.692dupT

p.Leu232AlafsTer12

p.L232Afs*12

P52735

protein_coding

TCGA-LD-A66U-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

VAV2

SNV

Missense_Mutation

c.1414N>A

p.Gly472Arg

p.G472R

P52735

protein_coding

deleterious(0.01)

probably_damaging(0.999)

TCGA-EA-A3HQ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

VAV2

SNV

Missense_Mutation

c.80N>G

p.Ser27Trp

p.S27W

P52735

protein_coding

deleterious(0.01)

probably_damaging(0.989)

TCGA-EK-A2RK-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

VAV2

SNV

Missense_Mutation

c.2001C>A

p.Asp667Glu

p.D667E

P52735

protein_coding

tolerated(0.05)

benign(0.05)

TCGA-FU-A3HZ-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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