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: CHMP2A

Gene summary for CHMP2A

Gene summary.

Gene information	Species	Human
	Gene symbol	CHMP2A
	Gene ID	27243
	Gene name	charged multivesicular body protein 2A
	Gene Alias	BC-2
	Cytomap	19q13.43
	Gene Type	protein-coding
	GO ID	GO:0000070
	UniProtAcc	A0A024R4S0

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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
27243	CHMP2A	GSM4909286	Human	Breast	IDC	5.62e-07	-3.08e-01	0.1081
27243	CHMP2A	GSM4909287	Human	Breast	IDC	3.30e-03	-3.23e-01	0.2057
27243	CHMP2A	GSM4909294	Human	Breast	IDC	3.04e-66	9.18e-01	0.2022
27243	CHMP2A	GSM4909296	Human	Breast	IDC	1.35e-06	-3.47e-02	0.1524
27243	CHMP2A	GSM4909297	Human	Breast	IDC	1.66e-15	-1.42e-01	0.1517
27243	CHMP2A	GSM4909301	Human	Breast	IDC	2.51e-05	3.11e-01	0.1577
27243	CHMP2A	GSM4909302	Human	Breast	IDC	4.26e-08	2.82e-01	0.1545
27243	CHMP2A	GSM4909307	Human	Breast	IDC	2.41e-10	4.08e-01	0.1569
27243	CHMP2A	GSM4909308	Human	Breast	IDC	6.32e-18	5.22e-01	0.158
27243	CHMP2A	GSM4909311	Human	Breast	IDC	1.01e-32	-2.68e-01	0.1534
27243	CHMP2A	GSM4909312	Human	Breast	IDC	5.17e-10	-1.41e-01	0.1552
27243	CHMP2A	GSM4909313	Human	Breast	IDC	1.08e-04	2.92e-02	0.0391
27243	CHMP2A	GSM4909317	Human	Breast	IDC	1.57e-04	3.32e-01	0.1355
27243	CHMP2A	GSM4909318	Human	Breast	IDC	2.16e-10	5.22e-01	0.2031
27243	CHMP2A	GSM4909319	Human	Breast	IDC	1.04e-48	-1.18e-01	0.1563
27243	CHMP2A	GSM4909320	Human	Breast	IDC	4.07e-08	1.06e-01	0.1575
27243	CHMP2A	GSM4909321	Human	Breast	IDC	2.64e-18	1.15e-01	0.1559
27243	CHMP2A	brca1	Human	Breast	Precancer	5.44e-13	4.28e-01	-0.0338
27243	CHMP2A	brca2	Human	Breast	Precancer	2.52e-11	4.24e-01	-0.024
27243	CHMP2A	brca3	Human	Breast	Precancer	4.00e-12	3.51e-01	-0.0263

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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:00160329	Breast	Precancer	viral process	58/1080	415/18723	3.42e-10	3.16e-08	58
GO:00190589	Breast	Precancer	viral life cycle	47/1080	317/18723	2.42e-09	1.99e-07	47
GO:00444039	Breast	Precancer	biological process involved in symbiotic interaction	42/1080	290/18723	3.40e-08	2.11e-06	42
GO:00521269	Breast	Precancer	movement in host environment	29/1080	175/18723	2.59e-07	1.28e-05	29
GO:00517019	Breast	Precancer	biological process involved in interaction with host	31/1080	203/18723	6.52e-07	2.71e-05	31
GO:00507929	Breast	Precancer	regulation of viral process	27/1080	164/18723	7.59e-07	3.05e-05	27
GO:00439039	Breast	Precancer	regulation of biological process involved in symbiotic interaction	15/1080	72/18723	1.23e-05	3.17e-04	15
GO:19039009	Breast	Precancer	regulation of viral life cycle	23/1080	148/18723	1.31e-05	3.30e-04	23
GO:00485249	Breast	Precancer	positive regulation of viral process	12/1080	65/18723	3.00e-04	4.34e-03	12
GO:00224119	Breast	Precancer	cellular component disassembly	44/1080	443/18723	3.17e-04	4.51e-03	44
GO:19035434	Breast	Precancer	positive regulation of exosomal secretion	5/1080	15/18723	1.17e-03	1.26e-02	5
GO:19035416	Breast	Precancer	regulation of exosomal secretion	5/1080	17/18723	2.19e-03	2.06e-02	5
GO:19901826	Breast	Precancer	exosomal secretion	5/1080	20/18723	4.74e-03	3.61e-02	5
GO:19039026	Breast	Precancer	positive regulation of viral life cycle	6/1080	29/18723	5.49e-03	4.01e-02	6
GO:00977346	Breast	Precancer	extracellular exosome biogenesis	5/1080	21/18723	5.93e-03	4.21e-02	5
GO:001603214	Breast	IDC	viral process	75/1434	415/18723	1.98e-12	4.02e-10	75
GO:001905814	Breast	IDC	viral life cycle	61/1434	317/18723	1.61e-11	2.77e-09	61
GO:004440314	Breast	IDC	biological process involved in symbiotic interaction	52/1434	290/18723	6.55e-09	5.03e-07	52
GO:005079214	Breast	IDC	regulation of viral process	36/1434	164/18723	6.55e-09	5.03e-07	36
GO:190390014	Breast	IDC	regulation of viral life cycle	30/1434	148/18723	7.25e-07	3.35e-05	30

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0414416	Breast	DCIS	Endocytosis	37/846	251/8465	9.92e-03	4.40e-02	3.24e-02	37
hsa0414417	Breast	DCIS	Endocytosis	37/846	251/8465	9.92e-03	4.40e-02	3.24e-02	37
hsa0414418	Cervix	CC	Endocytosis	64/1267	251/8465	6.97e-06	6.10e-05	3.61e-05	64
hsa0414419	Cervix	CC	Endocytosis	64/1267	251/8465	6.97e-06	6.10e-05	3.61e-05	64
hsa04144	Colorectum	AD	Endocytosis	111/2092	251/8465	5.95e-12	1.42e-10	9.08e-11	111
hsa041441	Colorectum	AD	Endocytosis	111/2092	251/8465	5.95e-12	1.42e-10	9.08e-11	111
hsa041442	Colorectum	SER	Endocytosis	81/1580	251/8465	1.14e-07	2.36e-06	1.71e-06	81
hsa04217	Colorectum	SER	Necroptosis	47/1580	159/8465	5.21e-04	4.44e-03	3.22e-03	47
hsa041443	Colorectum	SER	Endocytosis	81/1580	251/8465	1.14e-07	2.36e-06	1.71e-06	81
hsa042171	Colorectum	SER	Necroptosis	47/1580	159/8465	5.21e-04	4.44e-03	3.22e-03	47
hsa041444	Colorectum	MSS	Endocytosis	102/1875	251/8465	1.85e-11	4.43e-10	2.71e-10	102
hsa041445	Colorectum	MSS	Endocytosis	102/1875	251/8465	1.85e-11	4.43e-10	2.71e-10	102
hsa0414420	Endometrium	AEH	Endocytosis	56/1197	251/8465	2.58e-04	2.15e-03	1.57e-03	56
hsa04144110	Endometrium	AEH	Endocytosis	56/1197	251/8465	2.58e-04	2.15e-03	1.57e-03	56
hsa0414424	Endometrium	EEC	Endocytosis	57/1237	251/8465	3.34e-04	2.82e-03	2.10e-03	57
hsa0414434	Endometrium	EEC	Endocytosis	57/1237	251/8465	3.34e-04	2.82e-03	2.10e-03	57
hsa0414429	Esophagus	HGIN	Endocytosis	76/1383	251/8465	1.74e-08	3.34e-07	2.65e-07	76
hsa04144113	Esophagus	HGIN	Endocytosis	76/1383	251/8465	1.74e-08	3.34e-07	2.65e-07	76
hsa04144210	Esophagus	ESCC	Endocytosis	186/4205	251/8465	9.74e-16	4.66e-14	2.39e-14	186
hsa0414437	Esophagus	ESCC	Endocytosis	186/4205	251/8465	9.74e-16	4.66e-14	2.39e-14	186

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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

CHMP2A

SNV

Missense_Mutation

novel

c.423N>C

p.Glu141Asp

p.E141D

O43633

protein_coding

tolerated(0.06)

possibly_damaging(0.717)

TCGA-AC-A3W6-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

CHMP2A

SNV

Missense_Mutation

novel

c.445G>A

p.Asp149Asn

p.D149N

O43633

protein_coding

tolerated(0.09)

possibly_damaging(0.817)

TCGA-AC-A5XS-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

femara

CHMP2A

SNV

Missense_Mutation

novel

c.289N>G

p.Asn97Asp

p.N97D

O43633

protein_coding

tolerated(0.41)

benign(0.021)

TCGA-AA-3814-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

CHMP2A

SNV

Missense_Mutation

rs376979258

c.220C>T

p.Arg74Cys

p.R74C

O43633

protein_coding

deleterious(0.01)

possibly_damaging(0.806)

TCGA-AA-A00N-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

CHMP2A

SNV

Missense_Mutation

rs144804005

c.539N>T

p.Ser180Leu

p.S180L

O43633

protein_coding

tolerated(0.32)

benign(0.022)

TCGA-CK-4951-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

CHMP2A

SNV

Missense_Mutation

novel

c.152N>T

p.Ala51Val

p.A51V

O43633

protein_coding

deleterious(0.02)

probably_damaging(1)

TCGA-AG-A002-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

CHMP2A

SNV

Missense_Mutation

c.605C>T

p.Ala202Val

p.A202V

O43633

protein_coding

tolerated(0.07)

benign(0.017)

TCGA-A5-A0VP-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

CHMP2A

SNV

Missense_Mutation

novel

c.308N>C

p.Met103Thr

p.M103T

O43633

protein_coding

deleterious(0)

possibly_damaging(0.838)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

CHMP2A

SNV

Missense_Mutation

novel

c.497A>C

p.Gln166Pro

p.Q166P

O43633

protein_coding

deleterious(0)

probably_damaging(0.936)

TCGA-A5-A2K5-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

CHMP2A

SNV

Missense_Mutation

novel

c.178N>T

p.Arg60Cys

p.R60C

O43633

protein_coding

deleterious(0)

probably_damaging(0.932)

TCGA-AJ-A3OJ-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

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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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