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: ATP6V0E2

Gene summary for ATP6V0E2

Gene summary.

Gene information	Species	Human
	Gene symbol	ATP6V0E2
	Gene ID	155066
	Gene name	ATPase H+ transporting V0 subunit e2
	Gene Alias	ATP6V0E2L
	Cytomap	7q36.1
	Gene Type	protein-coding
	GO ID	GO:0006810
	UniProtAcc	E9PAS2

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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
155066	ATP6V0E2	GSM4909286	Human	Breast	IDC	1.66e-07	2.41e-01	0.1081
155066	ATP6V0E2	GSM4909293	Human	Breast	IDC	1.51e-05	1.78e-01	0.1581
155066	ATP6V0E2	GSM4909298	Human	Breast	IDC	6.03e-25	5.20e-01	0.1551
155066	ATP6V0E2	GSM4909304	Human	Breast	IDC	1.90e-03	2.05e-01	0.1636
155066	ATP6V0E2	GSM4909306	Human	Breast	IDC	1.47e-09	3.44e-01	0.1564
155066	ATP6V0E2	GSM4909308	Human	Breast	IDC	4.03e-02	1.38e-01	0.158
155066	ATP6V0E2	GSM4909311	Human	Breast	IDC	2.83e-03	2.84e-02	0.1534
155066	ATP6V0E2	GSM4909315	Human	Breast	IDC	1.55e-02	2.52e-01	0.21
155066	ATP6V0E2	GSM4909316	Human	Breast	IDC	2.25e-07	5.14e-01	0.21
155066	ATP6V0E2	GSM4909319	Human	Breast	IDC	6.72e-05	-7.36e-03	0.1563
155066	ATP6V0E2	DCIS2	Human	Breast	DCIS	3.05e-14	3.72e-02	0.0085
155066	ATP6V0E2	LZE4T	Human	Esophagus	ESCC	1.85e-07	2.35e-01	0.0811
155066	ATP6V0E2	LZE7T	Human	Esophagus	ESCC	4.43e-10	6.27e-01	0.0667
155066	ATP6V0E2	LZE24T	Human	Esophagus	ESCC	3.07e-13	2.91e-01	0.0596
155066	ATP6V0E2	LZE6T	Human	Esophagus	ESCC	3.32e-07	2.80e-01	0.0845
155066	ATP6V0E2	P1T-E	Human	Esophagus	ESCC	1.83e-02	1.58e-01	0.0875
155066	ATP6V0E2	P2T-E	Human	Esophagus	ESCC	8.31e-06	1.49e-01	0.1177
155066	ATP6V0E2	P4T-E	Human	Esophagus	ESCC	8.00e-13	3.47e-01	0.1323
155066	ATP6V0E2	P5T-E	Human	Esophagus	ESCC	3.54e-08	1.95e-01	0.1327
155066	ATP6V0E2	P8T-E	Human	Esophagus	ESCC	3.44e-09	2.07e-01	0.0889

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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
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
Prostate		BPH: Benign Prostatic Hyperplasia
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:190260012	Breast	IDC	proton transmembrane transport	40/1434	157/18723	7.34e-12	1.34e-09	40
GO:190260022	Breast	DCIS	proton transmembrane transport	40/1390	157/18723	2.77e-12	5.80e-10	40
GO:001623617	Esophagus	ESCC	macroautophagy	216/8552	291/18723	1.94e-23	4.57e-21	216
GO:001050617	Esophagus	ESCC	regulation of autophagy	220/8552	317/18723	6.72e-18	6.36e-16	220
GO:001624114	Esophagus	ESCC	regulation of macroautophagy	102/8552	141/18723	1.09e-10	3.27e-09	102
GO:00070353	Esophagus	ESCC	vacuolar acidification	20/8552	24/18723	1.69e-04	1.11e-03	20
GO:00514521	Esophagus	ESCC	intracellular pH reduction	29/8552	42/18723	1.87e-03	8.46e-03	29
GO:00458511	Esophagus	ESCC	pH reduction	31/8552	46/18723	2.42e-03	1.06e-02	31
GO:190260018	Esophagus	ESCC	proton transmembrane transport	88/8552	157/18723	5.62e-03	2.10e-02	88
GO:001623611	Liver	Cirrhotic	macroautophagy	129/4634	291/18723	1.75e-13	1.41e-11	129
GO:001050611	Liver	Cirrhotic	regulation of autophagy	132/4634	317/18723	2.17e-11	1.33e-09	132
GO:00162414	Liver	Cirrhotic	regulation of macroautophagy	60/4634	141/18723	2.57e-06	4.63e-05	60
GO:0007035	Liver	Cirrhotic	vacuolar acidification	15/4634	24/18723	9.76e-05	1.03e-03	15
GO:0051452	Liver	Cirrhotic	intracellular pH reduction	21/4634	42/18723	3.57e-04	3.03e-03	21
GO:0045851	Liver	Cirrhotic	pH reduction	22/4634	46/18723	5.75e-04	4.48e-03	22
GO:00300045	Liver	Cirrhotic	cellular monovalent inorganic cation homeostasis	38/4634	103/18723	4.02e-03	2.17e-02	38
GO:00306415	Liver	Cirrhotic	regulation of cellular pH	31/4634	81/18723	4.76e-03	2.50e-02	31
GO:00068853	Liver	Cirrhotic	regulation of pH	33/4634	91/18723	9.39e-03	4.29e-02	33
GO:001623621	Liver	HCC	macroautophagy	204/7958	291/18723	8.66e-22	1.41e-19	204
GO:001050621	Liver	HCC	regulation of autophagy	210/7958	317/18723	7.59e-18	8.45e-16	210

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0019023	Breast	IDC	Oxidative phosphorylation	62/867	134/8465	4.78e-27	2.59e-25	1.94e-25	62
hsa0511022	Breast	IDC	Vibrio cholerae infection	17/867	50/8465	4.82e-06	6.82e-05	5.10e-05	17
hsa0414522	Breast	IDC	Phagosome	34/867	152/8465	8.00e-06	9.99e-05	7.48e-05	34
hsa0532321	Breast	IDC	Rheumatoid arthritis	21/867	93/8465	3.69e-04	3.15e-03	2.36e-03	21
hsa0512022	Breast	IDC	Epithelial cell signaling in Helicobacter pylori infection	16/867	70/8465	1.56e-03	1.13e-02	8.42e-03	16
hsa0019033	Breast	IDC	Oxidative phosphorylation	62/867	134/8465	4.78e-27	2.59e-25	1.94e-25	62
hsa0511032	Breast	IDC	Vibrio cholerae infection	17/867	50/8465	4.82e-06	6.82e-05	5.10e-05	17
hsa0414532	Breast	IDC	Phagosome	34/867	152/8465	8.00e-06	9.99e-05	7.48e-05	34
hsa0532331	Breast	IDC	Rheumatoid arthritis	21/867	93/8465	3.69e-04	3.15e-03	2.36e-03	21
hsa0512032	Breast	IDC	Epithelial cell signaling in Helicobacter pylori infection	16/867	70/8465	1.56e-03	1.13e-02	8.42e-03	16
hsa0512041	Breast	DCIS	Epithelial cell signaling in Helicobacter pylori infection	15/846	70/8465	3.31e-03	1.98e-02	1.46e-02	15
hsa0512051	Breast	DCIS	Epithelial cell signaling in Helicobacter pylori infection	15/846	70/8465	3.31e-03	1.98e-02	1.46e-02	15
hsa00190210	Esophagus	ESCC	Oxidative phosphorylation	104/4205	134/8465	2.04e-11	2.98e-10	1.53e-10	104
hsa0516510	Esophagus	ESCC	Human papillomavirus infection	215/4205	331/8465	7.86e-09	7.12e-08	3.65e-08	215
hsa0512018	Esophagus	ESCC	Epithelial cell signaling in Helicobacter pylori infection	52/4205	70/8465	2.17e-05	1.07e-04	5.47e-05	52
hsa0414530	Esophagus	ESCC	Phagosome	100/4205	152/8465	3.81e-05	1.72e-04	8.82e-05	100
hsa0532320	Esophagus	ESCC	Rheumatoid arthritis	59/4205	93/8465	4.98e-03	1.27e-02	6.52e-03	59
hsa0511028	Esophagus	ESCC	Vibrio cholerae infection	34/4205	50/8465	6.62e-03	1.62e-02	8.30e-03	34
hsa0019038	Esophagus	ESCC	Oxidative phosphorylation	104/4205	134/8465	2.04e-11	2.98e-10	1.53e-10	104
hsa0516515	Esophagus	ESCC	Human papillomavirus infection	215/4205	331/8465	7.86e-09	7.12e-08	3.65e-08	215

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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

ATP6V0E2

SNV

Missense_Mutation

c.553N>G

p.Leu185Val

p.L185V

protein_coding

deleterious_low_confidence(0)

benign(0.036)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ATP6V0E2

SNV

Missense_Mutation

rs762511980

c.280G>A

p.Ala94Thr

p.A94T

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(1)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ATP6V0E2

SNV

Missense_Mutation

rs764371935

c.416N>T

p.Pro139Leu

p.P139L

protein_coding

deleterious_low_confidence(0.01)

benign(0.025)

TCGA-CK-4952-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Unknown

ATP6V0E2

SNV

Missense_Mutation

novel

c.412G>A

p.Asp138Asn

p.D138N

protein_coding

tolerated_low_confidence(0.05)

benign(0.001)

TCGA-F5-6814-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

ATP6V0E2

SNV

Missense_Mutation

rs762511980

c.280G>A

p.Ala94Thr

p.A94T

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(1)

TCGA-AP-A051-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

ATP6V0E2

SNV

Missense_Mutation

rs763116358

c.502N>A

p.Gly168Ser

p.G168S

protein_coding

deleterious_low_confidence(0)

benign(0.159)

TCGA-EO-A22U-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

ATP6V0E2

SNV

Missense_Mutation

novel

c.394N>T

p.Leu132Phe

p.L132F

protein_coding

deleterious_low_confidence(0)

benign(0)

TCGA-PG-A914-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

ATP6V0E2

insertion

Frame_Shift_Ins

novel

c.577dupG

p.Glu193GlyfsTer61

p.E193Gfs*61

protein_coding

TCGA-BG-A222-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

ATP6V0E2

SNV

Missense_Mutation

novel

c.158N>G

p.His53Arg

p.H53R

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(0.963)

TCGA-LG-A9QC-01

Liver

liver hepatocellular carcinoma

Male

<65

I/II

Unknown

ATP6V0E2

SNV

Missense_Mutation

rs762241479

c.509G>T

p.Gly170Val

p.G170V

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.722)

TCGA-VQ-A8E3-01

Stomach

stomach adenocarcinoma

Male

>=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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