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: ATP6V0A2

Gene summary for ATP6V0A2

Gene summary.

Gene information	Species	Human
	Gene symbol	ATP6V0A2
	Gene ID	23545
	Gene name	ATPase H+ transporting V0 subunit a2
	Gene Alias	A2
	Cytomap	12q24.31
	Gene Type	protein-coding
	GO ID	GO:0002376
	UniProtAcc	Q9Y487

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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
23545	ATP6V0A2	C21	Human	Oral cavity	OSCC	8.00e-06	3.30e-01	0.2678
23545	ATP6V0A2	C30	Human	Oral cavity	OSCC	1.57e-08	5.71e-01	0.3055
23545	ATP6V0A2	C38	Human	Oral cavity	OSCC	4.39e-03	4.37e-01	0.172
23545	ATP6V0A2	C43	Human	Oral cavity	OSCC	4.64e-02	8.83e-02	0.1704
23545	ATP6V0A2	C57	Human	Oral cavity	OSCC	2.83e-03	2.04e-01	0.1679
23545	ATP6V0A2	C08	Human	Oral cavity	OSCC	4.20e-06	1.75e-01	0.1919
23545	ATP6V0A2	LN22	Human	Oral cavity	OSCC	4.73e-02	5.58e-01	0.1733
23545	ATP6V0A2	EOLP-1	Human	Oral cavity	EOLP	1.33e-10	3.19e-01	-0.0202
23545	ATP6V0A2	EOLP-2	Human	Oral cavity	EOLP	1.35e-08	3.19e-01	-0.0203
23545	ATP6V0A2	SYSMH2	Human	Oral cavity	OSCC	4.97e-05	1.69e-01	0.2326
23545	ATP6V0A2	SYSMH3	Human	Oral cavity	OSCC	2.21e-10	2.56e-01	0.2442

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma

∗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:001623610	Oral cavity	OSCC	macroautophagy	192/7305	291/18723	7.01e-21	1.14e-18	192
GO:001050610	Oral cavity	OSCC	regulation of autophagy	198/7305	317/18723	1.63e-17	1.51e-15	198
GO:007048219	Oral cavity	OSCC	response to oxygen levels	200/7305	347/18723	1.17e-12	5.13e-11	200
GO:00162417	Oral cavity	OSCC	regulation of macroautophagy	96/7305	141/18723	2.33e-12	9.75e-11	96
GO:005507610	Oral cavity	OSCC	transition metal ion homeostasis	81/7305	138/18723	2.13e-06	2.72e-05	81
GO:007145317	Oral cavity	OSCC	cellular response to oxygen levels	98/7305	177/18723	7.10e-06	7.75e-05	98
GO:00469168	Oral cavity	OSCC	cellular transition metal ion homeostasis	64/7305	115/18723	2.13e-04	1.40e-03	64
GO:00070352	Oral cavity	OSCC	vacuolar acidification	17/7305	24/18723	1.59e-03	7.56e-03	17
GO:00362962	Oral cavity	OSCC	response to increased oxygen levels	20/7305	30/18723	1.99e-03	9.23e-03	20
GO:00550728	Oral cavity	OSCC	iron ion homeostasis	46/7305	85/18723	3.31e-03	1.42e-02	46
GO:00362954	Oral cavity	OSCC	cellular response to increased oxygen levels	10/7305	14/18723	1.44e-02	4.69e-02	10
GO:001050622	Oral cavity	EOLP	regulation of autophagy	74/2218	317/18723	5.84e-09	3.07e-07	74
GO:001623622	Oral cavity	EOLP	macroautophagy	65/2218	291/18723	2.74e-07	8.26e-06	65
GO:001624121	Oral cavity	EOLP	regulation of macroautophagy	38/2218	141/18723	7.18e-07	1.83e-05	38
GO:007048224	Oral cavity	EOLP	response to oxygen levels	70/2218	347/18723	5.00e-06	1.02e-04	70
GO:007145318	Oral cavity	EOLP	cellular response to oxygen levels	36/2218	177/18723	7.88e-04	6.25e-03	36
GO:005507624	Oral cavity	EOLP	transition metal ion homeostasis	27/2218	138/18723	5.80e-03	2.94e-02	27

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa051659	Oral cavity	OSCC	Human papillomavirus infection	200/3704	331/8465	3.83e-10	4.93e-09	2.51e-09	200
hsa041425	Oral cavity	OSCC	Lysosome	87/3704	132/8465	1.97e-07	1.35e-06	6.86e-07	87
hsa0019028	Oral cavity	OSCC	Oxidative phosphorylation	88/3704	134/8465	2.15e-07	1.44e-06	7.32e-07	88
hsa0512010	Oral cavity	OSCC	Epithelial cell signaling in Helicobacter pylori infection	49/3704	70/8465	7.57e-06	3.59e-05	1.83e-05	49
hsa051526	Oral cavity	OSCC	Tuberculosis	105/3704	180/8465	5.00e-05	2.04e-04	1.04e-04	105
hsa0414528	Oral cavity	OSCC	Phagosome	88/3704	152/8465	2.83e-04	9.13e-04	4.65e-04	88
hsa0532318	Oral cavity	OSCC	Rheumatoid arthritis	56/3704	93/8465	9.72e-04	2.76e-03	1.40e-03	56
hsa0511026	Oral cavity	OSCC	Vibrio cholerae infection	32/3704	50/8465	3.05e-03	7.74e-03	3.94e-03	32
hsa0516514	Oral cavity	OSCC	Human papillomavirus infection	200/3704	331/8465	3.83e-10	4.93e-09	2.51e-09	200
hsa0414212	Oral cavity	OSCC	Lysosome	87/3704	132/8465	1.97e-07	1.35e-06	6.86e-07	87
hsa00190112	Oral cavity	OSCC	Oxidative phosphorylation	88/3704	134/8465	2.15e-07	1.44e-06	7.32e-07	88
hsa0512017	Oral cavity	OSCC	Epithelial cell signaling in Helicobacter pylori infection	49/3704	70/8465	7.57e-06	3.59e-05	1.83e-05	49
hsa0515211	Oral cavity	OSCC	Tuberculosis	105/3704	180/8465	5.00e-05	2.04e-04	1.04e-04	105
hsa04145113	Oral cavity	OSCC	Phagosome	88/3704	152/8465	2.83e-04	9.13e-04	4.65e-04	88
hsa0532319	Oral cavity	OSCC	Rheumatoid arthritis	56/3704	93/8465	9.72e-04	2.76e-03	1.40e-03	56
hsa05110111	Oral cavity	OSCC	Vibrio cholerae infection	32/3704	50/8465	3.05e-03	7.74e-03	3.94e-03	32
hsa0516541	Oral cavity	EOLP	Human papillomavirus infection	79/1218	331/8465	1.96e-06	1.63e-05	9.60e-06	79
hsa0515241	Oral cavity	EOLP	Tuberculosis	47/1218	180/8465	2.19e-05	1.18e-04	6.96e-05	47
hsa0019045	Oral cavity	EOLP	Oxidative phosphorylation	36/1218	134/8465	1.05e-04	4.57e-04	2.69e-04	36
hsa0414543	Oral cavity	EOLP	Phagosome	38/1218	152/8465	3.42e-04	1.42e-03	8.35e-04	38

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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

ATP6V0A2

SNV

Missense_Mutation

c.655N>C

p.Val219Leu

p.V219L

Q9Y487

protein_coding

tolerated(0.53)

benign(0.038)

TCGA-A2-A0SY-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

arimidex

ATP6V0A2

SNV

Missense_Mutation

novel

c.720N>T

p.Lys240Asn

p.K240N

Q9Y487

protein_coding

deleterious(0.01)

probably_damaging(0.986)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ATP6V0A2

insertion

Nonsense_Mutation

novel

c.1021_1022insTTTGTGTTTAAACCTGTTCAGTGATTCCCAGCC

p.Ala341delinsValCysValTerThrCysSerValIleProSerPro

p.A341delinsVCV*TCSVIPSP

Q9Y487

protein_coding

TCGA-AN-A0G0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ATP6V0A2

insertion

In_Frame_Ins

novel

c.1416_1417insCCAGCACATTGGGAGGCTGAGACAGGTGGA

p.Phe472_Ser473insProAlaHisTrpGluAlaGluThrGlyGly

p.F472_S473insPAHWEAETGG

Q9Y487

protein_coding

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

ATP6V0A2

insertion

In_Frame_Ins

novel

c.2102_2103insTTTGAGACTGGAGTCTTC

p.Leu701delinsPheLeuArgLeuGluSerSer

p.L701delinsFLRLESS

Q9Y487

protein_coding

TCGA-B6-A0I6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ATP6V0A2

SNV

Missense_Mutation

novel

c.2261T>G

p.Leu754Arg

p.L754R

Q9Y487

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-VS-A9U6-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ATP6V0A2

SNV

Missense_Mutation

novel

c.1105N>T

p.Arg369Trp

p.R369W

Q9Y487

protein_coding

deleterious(0)

benign(0.045)

TCGA-VS-A9V3-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ATP6V0A2

SNV

Missense_Mutation

rs752522705

c.2290N>A

p.Ala764Thr

p.A764T

Q9Y487

protein_coding

deleterious(0)

probably_damaging(0.991)

TCGA-5M-AAT6-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Unknown

ATP6V0A2

SNV

Missense_Mutation

rs745357777

c.775C>T

p.Arg259Trp

p.R259W

Q9Y487

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-AA-3947-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

ATP6V0A2

SNV

Missense_Mutation

c.1516N>A

p.Asp506Asn

p.D506N

Q9Y487

protein_coding

tolerated(0.36)

benign(0.005)

TCGA-D5-6927-01

Colorectum

colon 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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