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: SCAMP2

Gene summary for SCAMP2

Gene summary.

Gene information	Species	Human
	Gene symbol	SCAMP2
	Gene ID	10066
	Gene name	secretory carrier membrane protein 2
	Gene Alias	SCAMP2
	Cytomap	15q24.1
	Gene Type	protein-coding
	GO ID	GO:0006810
	UniProtAcc	A8K769

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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
10066	SCAMP2	SYSMH1	Human	Oral cavity	OSCC	7.12e-22	4.79e-01	0.1127
10066	SCAMP2	SYSMH2	Human	Oral cavity	OSCC	6.80e-19	5.00e-01	0.2326
10066	SCAMP2	SYSMH3	Human	Oral cavity	OSCC	1.48e-23	5.97e-01	0.2442
10066	SCAMP2	SYSMH4	Human	Oral cavity	OSCC	3.85e-02	8.84e-02	0.1226
10066	SCAMP2	SYSMH5	Human	Oral cavity	OSCC	1.12e-07	3.34e-01	0.0647
10066	SCAMP2	SYSMH6	Human	Oral cavity	OSCC	5.80e-08	3.89e-01	0.1275
10066	SCAMP2	P1_cSCC	Human	Skin	cSCC	2.53e-15	5.28e-01	0.0292
10066	SCAMP2	P2_cSCC	Human	Skin	cSCC	1.85e-04	2.57e-01	-0.024
10066	SCAMP2	P4_cSCC	Human	Skin	cSCC	1.03e-14	3.86e-01	-0.00290000000000005
10066	SCAMP2	P10_cSCC	Human	Skin	cSCC	1.07e-16	5.96e-01	0.1017
10066	SCAMP2	male-WTA	Human	Thyroid	PTC	3.41e-39	3.98e-01	0.1037
10066	SCAMP2	PTC01	Human	Thyroid	PTC	1.45e-13	2.96e-01	0.1899
10066	SCAMP2	PTC04	Human	Thyroid	PTC	1.14e-13	3.12e-01	0.1927
10066	SCAMP2	PTC05	Human	Thyroid	PTC	2.16e-21	7.35e-01	0.2065
10066	SCAMP2	PTC06	Human	Thyroid	PTC	1.05e-33	7.01e-01	0.2057
10066	SCAMP2	PTC07	Human	Thyroid	PTC	1.61e-35	5.55e-01	0.2044
10066	SCAMP2	ATC09	Human	Thyroid	ATC	3.54e-08	2.96e-01	0.2871
10066	SCAMP2	ATC12	Human	Thyroid	ATC	6.04e-16	3.14e-01	0.34
10066	SCAMP2	ATC13	Human	Thyroid	ATC	2.76e-30	5.87e-01	0.34
10066	SCAMP2	ATC1	Human	Thyroid	ATC	1.09e-08	3.42e-01	0.2878

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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:0048193	Colorectum	AD	Golgi vesicle transport	109/3918	296/18723	1.80e-10	1.68e-08	109
GO:0006892	Colorectum	AD	post-Golgi vesicle-mediated transport	45/3918	104/18723	2.22e-07	9.26e-06	45
GO:00481931	Colorectum	SER	Golgi vesicle transport	79/2897	296/18723	4.20e-07	2.15e-05	79
GO:00068921	Colorectum	SER	post-Golgi vesicle-mediated transport	31/2897	104/18723	1.59e-04	3.08e-03	31
GO:00481932	Colorectum	MSS	Golgi vesicle transport	101/3467	296/18723	9.09e-11	9.77e-09	101
GO:00068922	Colorectum	MSS	post-Golgi vesicle-mediated transport	40/3467	104/18723	1.45e-06	4.82e-05	40
GO:00481934	Colorectum	FAP	Golgi vesicle transport	77/2622	296/18723	2.86e-08	2.62e-06	77
GO:00068923	Colorectum	FAP	post-Golgi vesicle-mediated transport	36/2622	104/18723	9.23e-08	6.22e-06	36
GO:004819318	Esophagus	ESCC	Golgi vesicle transport	231/8552	296/18723	1.82e-30	9.63e-28	231
GO:000689215	Esophagus	ESCC	post-Golgi vesicle-mediated transport	82/8552	104/18723	4.00e-12	1.55e-10	82
GO:004819311	Liver	Cirrhotic	Golgi vesicle transport	153/4634	296/18723	1.02e-23	6.43e-21	153
GO:000689211	Liver	Cirrhotic	post-Golgi vesicle-mediated transport	51/4634	104/18723	7.12e-08	2.15e-06	51
GO:004819321	Liver	HCC	Golgi vesicle transport	217/7958	296/18723	2.58e-27	1.02e-24	217
GO:000689221	Liver	HCC	post-Golgi vesicle-mediated transport	77/7958	104/18723	6.14e-11	2.24e-09	77
GO:004819315	Oral cavity	OSCC	Golgi vesicle transport	209/7305	296/18723	1.39e-28	6.30e-26	209
GO:00068929	Oral cavity	OSCC	post-Golgi vesicle-mediated transport	71/7305	104/18723	1.37e-09	3.33e-08	71
GO:004819316	Oral cavity	LP	Golgi vesicle transport	141/4623	296/18723	6.11e-18	1.06e-15	141
GO:000689214	Oral cavity	LP	post-Golgi vesicle-mediated transport	44/4623	104/18723	5.90e-05	8.05e-04	44
GO:0048193110	Skin	cSCC	Golgi vesicle transport	153/4864	296/18723	1.85e-21	3.41e-19	153
GO:000689217	Skin	cSCC	post-Golgi vesicle-mediated transport	49/4864	104/18723	2.71e-06	4.30e-05	49

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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

SCAMP2

SNV

Missense_Mutation

novel

c.89C>A

p.Pro30Gln

p.P30Q

O15127

protein_coding

tolerated(0.57)

benign(0.003)

TCGA-A7-A0DB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

SCAMP2

SNV

Missense_Mutation

c.160C>T

p.Leu54Phe

p.L54F

O15127

protein_coding

tolerated(0.7)

benign(0.031)

TCGA-BH-A0B9-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

SCAMP2

SNV

Missense_Mutation

novel

c.177G>T

p.Gln59His

p.Q59H

O15127

protein_coding

deleterious(0.02)

benign(0.043)

TCGA-EA-A410-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SCAMP2

SNV

Missense_Mutation

c.836N>T

p.Ser279Leu

p.S279L

O15127

protein_coding

deleterious(0.01)

benign(0.1)

TCGA-MU-A51Y-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SCAMP2

SNV

Missense_Mutation

novel

c.335N>G

p.Asn112Ser

p.N112S

O15127

protein_coding

tolerated(1)

benign(0)

TCGA-F5-6814-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

SCAMP2

SNV

Missense_Mutation

novel

c.560N>T

p.Ser187Phe

p.S187F

O15127

protein_coding

deleterious(0.02)

probably_damaging(0.989)

TCGA-A5-A0G1-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

SCAMP2

SNV

Missense_Mutation

novel

c.572N>A

p.Phe191Tyr

p.F191Y

O15127

protein_coding

deleterious(0.01)

benign(0.319)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

SCAMP2

SNV

Missense_Mutation

rs746545894

c.440N>A

p.Arg147Gln

p.R147Q

O15127

protein_coding

deleterious(0.02)

possibly_damaging(0.487)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

SCAMP2

SNV

Missense_Mutation

novel

c.560N>T

p.Ser187Phe

p.S187F

O15127

protein_coding

deleterious(0.02)

probably_damaging(0.989)

TCGA-A5-A0GG-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

SCAMP2

SNV

Missense_Mutation

novel

c.861N>A

p.His287Gln

p.H287Q

O15127

protein_coding

deleterious(0)

probably_damaging(0.993)

TCGA-AX-A2HD-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

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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