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: VASP

Gene summary for VASP

Gene summary.

Gene information	Species	Human
	Gene symbol	VASP
	Gene ID	7408
	Gene name	vasodilator stimulated phosphoprotein
	Gene Alias	VASP
	Cytomap	19q13.32
	Gene Type	protein-coding
	GO ID	GO:0000902
	UniProtAcc	A0A024R0V4

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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
7408	VASP	P83T-E	Human	Esophagus	ESCC	3.53e-59	1.98e+00	0.1738
7408	VASP	P84T-E	Human	Esophagus	ESCC	2.42e-07	6.85e-01	0.0933
7408	VASP	P89T-E	Human	Esophagus	ESCC	1.42e-19	1.57e+00	0.1752
7408	VASP	P91T-E	Human	Esophagus	ESCC	3.65e-18	2.17e+00	0.1828
7408	VASP	P104T-E	Human	Esophagus	ESCC	1.48e-06	1.34e+00	0.0931
7408	VASP	P107T-E	Human	Esophagus	ESCC	4.64e-63	1.45e+00	0.171
7408	VASP	P126T-E	Human	Esophagus	ESCC	2.63e-12	1.26e+00	0.1125
7408	VASP	P127T-E	Human	Esophagus	ESCC	4.13e-20	4.86e-01	0.0826
7408	VASP	P128T-E	Human	Esophagus	ESCC	4.35e-36	1.34e+00	0.1241
7408	VASP	P130T-E	Human	Esophagus	ESCC	6.18e-56	1.22e+00	0.1676
7408	VASP	S43	Human	Liver	Cirrhotic	8.28e-06	-2.35e-01	-0.0187
7408	VASP	HCC1_Meng	Human	Liver	HCC	2.78e-71	-5.15e-02	0.0246
7408	VASP	HCC2_Meng	Human	Liver	HCC	9.96e-48	3.86e-01	0.0107
7408	VASP	cirrhotic1	Human	Liver	Cirrhotic	2.52e-02	-3.13e-02	0.0202
7408	VASP	cirrhotic2	Human	Liver	Cirrhotic	3.20e-04	6.75e-02	0.0201
7408	VASP	cirrhotic3	Human	Liver	Cirrhotic	4.26e-02	3.00e-03	0.0215
7408	VASP	HCC2	Human	Liver	HCC	4.32e-05	1.65e+00	0.5341
7408	VASP	Pt13.b	Human	Liver	HCC	6.19e-19	3.18e-01	0.0251
7408	VASP	S015	Human	Liver	HCC	3.02e-13	7.27e-01	0.2375
7408	VASP	S016	Human	Liver	HCC	8.05e-10	5.42e-01	0.2243

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:0007015	Colorectum	AD	actin filament organization	167/3918	442/18723	1.65e-16	7.94e-14	167
GO:0032535	Colorectum	AD	regulation of cellular component size	142/3918	383/18723	1.74e-13	3.41e-11	142
GO:1902903	Colorectum	AD	regulation of supramolecular fiber organization	139/3918	383/18723	2.01e-12	3.19e-10	139
GO:0032970	Colorectum	AD	regulation of actin filament-based process	142/3918	397/18723	4.05e-12	5.90e-10	142
GO:0110053	Colorectum	AD	regulation of actin filament organization	108/3918	278/18723	5.02e-12	6.98e-10	108
GO:0008154	Colorectum	AD	actin polymerization or depolymerization	90/3918	218/18723	6.14e-12	8.23e-10	90
GO:0032271	Colorectum	AD	regulation of protein polymerization	94/3918	233/18723	1.01e-11	1.29e-09	94
GO:0030041	Colorectum	AD	actin filament polymerization	81/3918	191/18723	1.35e-11	1.69e-09	81
GO:0051258	Colorectum	AD	protein polymerization	112/3918	297/18723	1.85e-11	2.27e-09	112
GO:0043254	Colorectum	AD	regulation of protein-containing complex assembly	148/3918	428/18723	2.64e-11	3.18e-09	148
GO:0008064	Colorectum	AD	regulation of actin polymerization or depolymerization	79/3918	188/18723	4.17e-11	4.74e-09	79
GO:0030833	Colorectum	AD	regulation of actin filament polymerization	74/3918	172/18723	4.50e-11	5.03e-09	74
GO:0030832	Colorectum	AD	regulation of actin filament length	79/3918	189/18723	5.71e-11	6.27e-09	79
GO:1902905	Colorectum	AD	positive regulation of supramolecular fiber organization	85/3918	209/18723	5.95e-11	6.33e-09	85
GO:0032956	Colorectum	AD	regulation of actin cytoskeleton organization	127/3918	358/18723	1.03e-10	1.04e-08	127
GO:0051495	Colorectum	AD	positive regulation of cytoskeleton organization	89/3918	226/18723	1.61e-10	1.56e-08	89
GO:0032273	Colorectum	AD	positive regulation of protein polymerization	62/3918	138/18723	1.94e-10	1.76e-08	62
GO:0031334	Colorectum	AD	positive regulation of protein-containing complex assembly	91/3918	237/18723	4.78e-10	3.99e-08	91
GO:0030838	Colorectum	AD	positive regulation of actin filament polymerization	48/3918	99/18723	9.21e-10	7.03e-08	48
GO:0007409	Colorectum	AD	axonogenesis	122/3918	418/18723	3.36e-05	6.15e-04	122

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa04530	Colorectum	AD	Tight junction	76/2092	169/8465	5.49e-09	9.69e-08	6.18e-08	76
hsa04666	Colorectum	AD	Fc gamma R-mediated phagocytosis	46/2092	97/8465	9.10e-07	1.22e-05	7.77e-06	46
hsa04015	Colorectum	AD	Rap1 signaling pathway	71/2092	210/8465	1.72e-03	9.68e-03	6.18e-03	71
hsa04510	Colorectum	AD	Focal adhesion	67/2092	203/8465	4.40e-03	2.17e-02	1.38e-02	67
hsa04670	Colorectum	AD	Leukocyte transendothelial migration	41/2092	114/8465	4.60e-03	2.20e-02	1.40e-02	41
hsa045301	Colorectum	AD	Tight junction	76/2092	169/8465	5.49e-09	9.69e-08	6.18e-08	76
hsa046661	Colorectum	AD	Fc gamma R-mediated phagocytosis	46/2092	97/8465	9.10e-07	1.22e-05	7.77e-06	46
hsa040151	Colorectum	AD	Rap1 signaling pathway	71/2092	210/8465	1.72e-03	9.68e-03	6.18e-03	71
hsa045101	Colorectum	AD	Focal adhesion	67/2092	203/8465	4.40e-03	2.17e-02	1.38e-02	67
hsa046701	Colorectum	AD	Leukocyte transendothelial migration	41/2092	114/8465	4.60e-03	2.20e-02	1.40e-02	41
hsa045302	Colorectum	SER	Tight junction	59/1580	169/8465	3.24e-07	5.98e-06	4.34e-06	59
hsa046662	Colorectum	SER	Fc gamma R-mediated phagocytosis	39/1580	97/8465	5.84e-07	9.70e-06	7.04e-06	39
hsa046702	Colorectum	SER	Leukocyte transendothelial migration	37/1580	114/8465	2.77e-04	2.56e-03	1.86e-03	37
hsa040152	Colorectum	SER	Rap1 signaling pathway	54/1580	210/8465	6.55e-03	3.68e-02	2.67e-02	54
hsa045303	Colorectum	SER	Tight junction	59/1580	169/8465	3.24e-07	5.98e-06	4.34e-06	59
hsa046663	Colorectum	SER	Fc gamma R-mediated phagocytosis	39/1580	97/8465	5.84e-07	9.70e-06	7.04e-06	39
hsa046703	Colorectum	SER	Leukocyte transendothelial migration	37/1580	114/8465	2.77e-04	2.56e-03	1.86e-03	37
hsa040153	Colorectum	SER	Rap1 signaling pathway	54/1580	210/8465	6.55e-03	3.68e-02	2.67e-02	54
hsa046664	Colorectum	MSS	Fc gamma R-mediated phagocytosis	45/1875	97/8465	9.30e-08	1.56e-06	9.55e-07	45
hsa045304	Colorectum	MSS	Tight junction	66/1875	169/8465	4.10e-07	6.25e-06	3.83e-06	66

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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

VASP

SNV

Missense_Mutation

rs374049612

c.988G>A

p.Glu330Lys

p.E330K

P50552

protein_coding

tolerated(0.27)

benign(0.335)

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

VASP

SNV

Missense_Mutation

novel

c.893G>C

p.Arg298Thr

p.R298T

P50552

protein_coding

tolerated(0.24)

possibly_damaging(0.614)

TCGA-GM-A2D9-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

VASP

insertion

Nonsense_Mutation

novel

c.1131_1132insAGTGGCCAGCCAGCTGGACAGTGAAGAATGA

p.Gly378SerfsTer8

p.G378Sfs*8

P50552

protein_coding

TCGA-AN-A0FN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

VASP

insertion

Frame_Shift_Ins

novel

c.956_956+1insAAAAAACCTCTTATTAACCCCAT

p.Met320LysfsTer8

p.M320Kfs*8

P50552

protein_coding

TCGA-BH-A0B3-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

VASP

SNV

Missense_Mutation

rs571015875

c.104N>A

p.Arg35His

p.R35H

P50552

protein_coding

deleterious(0.01)

benign(0.074)

TCGA-C5-A907-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

VASP

SNV

Missense_Mutation

c.760N>A

p.Glu254Lys

p.E254K

P50552

protein_coding

tolerated(0.09)

benign(0.023)

TCGA-EK-A2RJ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

VASP

SNV

Missense_Mutation

novel

c.1092G>T

p.Glu364Asp

p.E364D

P50552

protein_coding

tolerated(0.3)

benign(0.279)

TCGA-CA-6717-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Chemotherapy

oxaliplatin

VASP

SNV

Missense_Mutation

c.775N>A

p.Gly259Arg

p.G259R

P50552

protein_coding

deleterious(0)

benign(0.021)

TCGA-G4-6302-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

VASP

SNV

Missense_Mutation

novel

c.798G>T

p.Glu266Asp

p.E266D

P50552

protein_coding

deleterious(0)

probably_damaging(0.967)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

VASP

SNV

Missense_Mutation

novel

c.763A>G

p.Ser255Gly

p.S255G

P50552

protein_coding

tolerated(0.09)

benign(0)

TCGA-AP-A1DK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

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
7408	VASP	KINASE		hydrochlorothiazide	HYDROCHLOROTHIAZIDE

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