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: VAMP3

Gene summary for VAMP3

Gene summary.

Gene information	Species	Human
	Gene symbol	VAMP3
	Gene ID	9341
	Gene name	vesicle associated membrane protein 3
	Gene Alias	CEB
	Cytomap	1p36.23
	Gene Type	protein-coding
	GO ID	GO:0000902
	UniProtAcc	Q15836

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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
9341	VAMP3	HTA11_2487_2000001011	Human	Colorectum	SER	1.06e-04	3.49e-01	-0.1808
9341	VAMP3	HTA11_1938_2000001011	Human	Colorectum	AD	1.81e-11	5.72e-01	-0.0811
9341	VAMP3	HTA11_78_2000001011	Human	Colorectum	AD	4.41e-07	4.82e-01	-0.1088
9341	VAMP3	HTA11_347_2000001011	Human	Colorectum	AD	3.97e-12	4.21e-01	-0.1954
9341	VAMP3	HTA11_411_2000001011	Human	Colorectum	SER	3.30e-04	6.49e-01	-0.2602
9341	VAMP3	HTA11_3361_2000001011	Human	Colorectum	AD	2.24e-03	3.40e-01	-0.1207
9341	VAMP3	HTA11_866_2000001011	Human	Colorectum	AD	4.19e-03	1.98e-01	-0.1001
9341	VAMP3	HTA11_1391_2000001011	Human	Colorectum	AD	6.26e-09	4.60e-01	-0.059
9341	VAMP3	HTA11_5212_2000001011	Human	Colorectum	AD	4.62e-04	4.28e-01	-0.2061
9341	VAMP3	HTA11_99999970781_79442	Human	Colorectum	MSS	1.65e-08	3.73e-01	0.294
9341	VAMP3	HTA11_99999965104_69814	Human	Colorectum	MSS	5.98e-07	4.06e-01	0.281
9341	VAMP3	HTA11_99999971662_82457	Human	Colorectum	MSS	7.24e-14	4.91e-01	0.3859
9341	VAMP3	LZE4T	Human	Esophagus	ESCC	1.94e-17	3.84e-01	0.0811
9341	VAMP3	LZE5T	Human	Esophagus	ESCC	3.68e-06	6.16e-01	0.0514
9341	VAMP3	LZE8T	Human	Esophagus	ESCC	4.49e-11	4.58e-01	0.067
9341	VAMP3	LZE20T	Human	Esophagus	ESCC	5.55e-08	3.84e-01	0.0662
9341	VAMP3	LZE24T	Human	Esophagus	ESCC	8.19e-24	8.53e-01	0.0596
9341	VAMP3	LZE6T	Human	Esophagus	ESCC	1.85e-04	3.41e-01	0.0845
9341	VAMP3	P1T-E	Human	Esophagus	ESCC	1.81e-05	4.69e-01	0.0875
9341	VAMP3	P2T-E	Human	Esophagus	ESCC	1.17e-37	6.37e-01	0.1177

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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
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:0072659	Colorectum	AD	protein localization to plasma membrane	122/3918	284/18723	2.86e-17	1.49e-14	122
GO:1990778	Colorectum	AD	protein localization to cell periphery	129/3918	333/18723	5.51e-14	1.15e-11	129
GO:0090150	Colorectum	AD	establishment of protein localization to membrane	100/3918	260/18723	6.01e-11	6.33e-09	100
GO:0048193	Colorectum	AD	Golgi vesicle transport	109/3918	296/18723	1.80e-10	1.68e-08	109
GO:0016197	Colorectum	AD	endosomal transport	90/3918	230/18723	1.88e-10	1.73e-08	90
GO:0016482	Colorectum	AD	cytosolic transport	68/3918	168/18723	6.00e-09	3.72e-07	68
GO:0098876	Colorectum	AD	vesicle-mediated transport to the plasma membrane	57/3918	136/18723	2.30e-08	1.27e-06	57
GO:0061951	Colorectum	AD	establishment of protein localization to plasma membrane	31/3918	60/18723	1.37e-07	6.42e-06	31
GO:0016050	Colorectum	AD	vesicle organization	101/3918	300/18723	1.65e-07	7.17e-06	101
GO:0006892	Colorectum	AD	post-Golgi vesicle-mediated transport	45/3918	104/18723	2.22e-07	9.26e-06	45
GO:0031589	Colorectum	AD	cell-substrate adhesion	116/3918	363/18723	4.68e-07	1.76e-05	116
GO:0043112	Colorectum	AD	receptor metabolic process	62/3918	166/18723	8.18e-07	2.85e-05	62
GO:0043001	Colorectum	AD	Golgi to plasma membrane protein transport	21/3918	40/18723	1.03e-05	2.40e-04	21
GO:0042147	Colorectum	AD	retrograde transport, endosome to Golgi	37/3918	91/18723	1.46e-05	3.14e-04	37
GO:0001881	Colorectum	AD	receptor recycling	18/3918	33/18723	2.23e-05	4.40e-04	18
GO:0006893	Colorectum	AD	Golgi to plasma membrane transport	27/3918	60/18723	2.41e-05	4.66e-04	27
GO:0034446	Colorectum	AD	substrate adhesion-dependent cell spreading	40/3918	108/18723	8.52e-05	1.32e-03	40
GO:0022406	Colorectum	AD	membrane docking	31/3918	86/18723	8.67e-04	8.45e-03	31
GO:0001919	Colorectum	AD	regulation of receptor recycling	12/3918	23/18723	9.11e-04	8.71e-03	12
GO:0140056	Colorectum	AD	organelle localization by membrane tethering	28/3918	77/18723	1.29e-03	1.14e-02	28

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa041305	Esophagus	ESCC	SNARE interactions in vesicular transport	28/4205	33/8465	2.75e-05	1.32e-04	6.75e-05	28
hsa0414530	Esophagus	ESCC	Phagosome	100/4205	152/8465	3.81e-05	1.72e-04	8.82e-05	100
hsa0413012	Esophagus	ESCC	SNARE interactions in vesicular transport	28/4205	33/8465	2.75e-05	1.32e-04	6.75e-05	28
hsa04145114	Esophagus	ESCC	Phagosome	100/4205	152/8465	3.81e-05	1.72e-04	8.82e-05	100
hsa0414514	Liver	Cirrhotic	Phagosome	73/2530	152/8465	1.61e-06	1.78e-05	1.10e-05	73
hsa04130	Liver	Cirrhotic	SNARE interactions in vesicular transport	18/2530	33/8465	2.64e-03	1.10e-02	6.76e-03	18
hsa0414515	Liver	Cirrhotic	Phagosome	73/2530	152/8465	1.61e-06	1.78e-05	1.10e-05	73
hsa041301	Liver	Cirrhotic	SNARE interactions in vesicular transport	18/2530	33/8465	2.64e-03	1.10e-02	6.76e-03	18
hsa0414521	Liver	HCC	Phagosome	93/4020	152/8465	4.27e-04	1.88e-03	1.05e-03	93
hsa041302	Liver	HCC	SNARE interactions in vesicular transport	25/4020	33/8465	8.78e-04	3.38e-03	1.88e-03	25
hsa0414531	Liver	HCC	Phagosome	93/4020	152/8465	4.27e-04	1.88e-03	1.05e-03	93
hsa041303	Liver	HCC	SNARE interactions in vesicular transport	25/4020	33/8465	8.78e-04	3.38e-03	1.88e-03	25
hsa041304	Oral cavity	OSCC	SNARE interactions in vesicular transport	28/3704	33/8465	1.31e-06	7.18e-06	3.66e-06	28
hsa0414528	Oral cavity	OSCC	Phagosome	88/3704	152/8465	2.83e-04	9.13e-04	4.65e-04	88
hsa0413011	Oral cavity	OSCC	SNARE interactions in vesicular transport	28/3704	33/8465	1.31e-06	7.18e-06	3.66e-06	28
hsa04145113	Oral cavity	OSCC	Phagosome	88/3704	152/8465	2.83e-04	9.13e-04	4.65e-04	88
hsa0414529	Oral cavity	LP	Phagosome	73/2418	152/8465	2.37e-07	3.29e-06	2.12e-06	73
hsa0413021	Oral cavity	LP	SNARE interactions in vesicular transport	22/2418	33/8465	6.00e-06	4.76e-05	3.07e-05	22
hsa0414536	Oral cavity	LP	Phagosome	73/2418	152/8465	2.37e-07	3.29e-06	2.12e-06	73
hsa0413031	Oral cavity	LP	SNARE interactions in vesicular transport	22/2418	33/8465	6.00e-06	4.76e-05	3.07e-05	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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
VAMP3	CD8TRM	Pancreas	ADJ	CTSF,MLLT11,TBC1D22B, etc.	0.00e+00
VAMP3	CD8TCM	Pancreas	ADJ	CTSF,MLLT11,TBC1D22B, etc.	-2.22e-16
VAMP3	TREG	Pancreas	ADJ	CTSF,MLLT11,TBC1D22B, etc.	-2.22e-16
VAMP3	CD8TEREX	Pancreas	PDAC	CTSF,MLLT11,TBC1D22B, etc.	4.75e-03
VAMP3	CD8TEXP	Pancreas	PDAC	CTSF,MLLT11,TBC1D22B, etc.	1.35e-03
VAMP3	PLA	Pancreas	PDAC	CTSF,MLLT11,TBC1D22B, etc.	4.94e-04
VAMP3	GC	Pancreas	PDAC	CTSF,MLLT11,TBC1D22B, etc.	2.81e-04
VAMP3	MESC	Stomach	CAG with IM	ALPI,DUOX2,SLC40A1, etc.	4.38e-02
VAMP3	A.X	Stomach	SIM	ALPI,DUOX2,SLC40A1, etc.	2.20e-02

∗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

VAMP3

SNV

Missense_Mutation

c.146G>A

p.Arg49His

p.R49H

Q15836

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.998)

TCGA-AN-A0FX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

VAMP3

SNV

Missense_Mutation

c.57A>C

p.Gln19His

p.Q19H

Q15836

protein_coding

deleterious(0)

possibly_damaging(0.908)

TCGA-AZ-6607-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Unknown

VAMP3

SNV

Missense_Mutation

novel

c.135N>T

p.Glu45Asp

p.E45D

Q15836

protein_coding

deleterious_low_confidence(0.04)

benign(0.02)

TCGA-AG-3883-01

Colorectum

rectum adenocarcinoma

Male

>=65

I/II

Unknown

VAMP3

SNV

Missense_Mutation

novel

c.38G>A

p.Arg13Gln

p.R13Q

Q15836

protein_coding

deleterious(0)

benign(0.163)

TCGA-AG-A002-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

VAMP3

SNV

Missense_Mutation

novel

c.123G>T

p.Gln41His

p.Q41H

Q15836

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.895)

TCGA-DF-A2KN-01

Endometrium

uterine corpus endometrioid carcinoma

Female

Unknown

I/II

Unknown

VAMP3

SNV

Missense_Mutation

novel

c.89N>A

p.Arg30Gln

p.R30Q

Q15836

protein_coding

deleterious_low_confidence(0)

benign(0.313)

TCGA-DF-A2KU-01

Endometrium

uterine corpus endometrioid carcinoma

Female

Unknown

I/II

Unknown

VAMP3

SNV

Missense_Mutation

novel

c.5C>T

p.Ser2Phe

p.S2F

Q15836

protein_coding

deleterious_low_confidence(0.01)

benign(0.123)

TCGA-EO-A22X-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unspecific

Carboplatin

Complete Response

VAMP3

SNV

Missense_Mutation

c.100G>A

p.Asp34Asn

p.D34N

Q15836

protein_coding

deleterious_low_confidence(0.02)

benign(0.223)

TCGA-RC-A7SK-01

Liver

liver hepatocellular carcinoma

Male

<65

I/II

Unknown

VAMP3

SNV

Missense_Mutation

c.154N>T

p.Ala52Ser

p.A52S

Q15836

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.627)

TCGA-44-7667-01

Lung

lung adenocarcinoma

Female

<65

I/II

Unknown

VAMP3

SNV

Missense_Mutation

c.223A>T

p.Asn75Tyr

p.N75Y

Q15836

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.995)

TCGA-EL-A3MX-01

Thyroid

thyroid 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

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