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: PPP2R3A

Gene summary for PPP2R3A

Gene summary.

Gene information	Species	Human
	Gene symbol	PPP2R3A
	Gene ID	5523
	Gene name	protein phosphatase 2 regulatory subunit B''alpha
	Gene Alias	PPP2R3
	Cytomap	3q22.2-q22.3
	Gene Type	protein-coding
	GO ID	GO:0006464
	UniProtAcc	Q06190

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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
5523	PPP2R3A	CCI_1	Human	Cervix	CC	9.68e-08	8.40e-01	0.528
5523	PPP2R3A	CCI_2	Human	Cervix	CC	5.43e-04	1.44e+00	0.5249
5523	PPP2R3A	CCI_3	Human	Cervix	CC	3.57e-30	1.51e+00	0.516
5523	PPP2R3A	HTA11_3410_2000001011	Human	Colorectum	AD	2.79e-25	-7.04e-01	0.0155
5523	PPP2R3A	HTA11_2487_2000001011	Human	Colorectum	SER	5.09e-05	-5.09e-01	-0.1808
5523	PPP2R3A	HTA11_2951_2000001011	Human	Colorectum	AD	4.97e-05	-8.59e-01	0.0216
5523	PPP2R3A	HTA11_2112_2000001011	Human	Colorectum	SER	2.23e-02	-6.83e-01	-0.2196
5523	PPP2R3A	HTA11_3361_2000001011	Human	Colorectum	AD	4.29e-07	-5.97e-01	-0.1207
5523	PPP2R3A	HTA11_696_2000001011	Human	Colorectum	AD	1.45e-08	-4.34e-01	-0.1464
5523	PPP2R3A	HTA11_1391_2000001011	Human	Colorectum	AD	6.03e-05	-4.08e-01	-0.059
5523	PPP2R3A	HTA11_2992_2000001011	Human	Colorectum	SER	3.45e-02	-6.16e-01	-0.1706
5523	PPP2R3A	HTA11_5212_2000001011	Human	Colorectum	AD	3.55e-03	-6.46e-01	-0.2061
5523	PPP2R3A	HTA11_866_3004761011	Human	Colorectum	AD	4.08e-23	-7.73e-01	0.096
5523	PPP2R3A	HTA11_9408_2000001011	Human	Colorectum	AD	6.13e-04	-8.85e-01	0.0451
5523	PPP2R3A	HTA11_8622_2000001021	Human	Colorectum	SER	1.30e-05	-7.65e-01	0.0528
5523	PPP2R3A	HTA11_10711_2000001011	Human	Colorectum	AD	1.08e-11	-6.87e-01	0.0338
5523	PPP2R3A	HTA11_7696_3000711011	Human	Colorectum	AD	1.15e-20	-6.68e-01	0.0674
5523	PPP2R3A	HTA11_6818_2000001021	Human	Colorectum	AD	5.94e-03	-5.19e-01	0.0588
5523	PPP2R3A	HTA11_99999970781_79442	Human	Colorectum	MSS	1.12e-30	-7.52e-01	0.294
5523	PPP2R3A	HTA11_99999965104_69814	Human	Colorectum	MSS	1.34e-06	-5.97e-01	0.281

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
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
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ

∗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:00064708	Cervix	CC	protein dephosphorylation	60/2311	281/18723	1.33e-05	2.68e-04	60
GO:00163117	Cervix	CC	dephosphorylation	73/2311	417/18723	1.23e-03	9.87e-03	73
GO:0016311	Colorectum	AD	dephosphorylation	123/3918	417/18723	1.84e-05	3.82e-04	123
GO:0006470	Colorectum	AD	protein dephosphorylation	88/3918	281/18723	2.56e-05	4.89e-04	88
GO:00064701	Colorectum	SER	protein dephosphorylation	65/2897	281/18723	4.44e-04	6.51e-03	65
GO:00163111	Colorectum	SER	dephosphorylation	86/2897	417/18723	2.73e-03	2.46e-02	86
GO:00064702	Colorectum	MSS	protein dephosphorylation	73/3467	281/18723	1.15e-03	1.12e-02	73
GO:00163112	Colorectum	MSS	dephosphorylation	101/3467	417/18723	1.98e-03	1.70e-02	101
GO:00163113	Colorectum	FAP	dephosphorylation	95/2622	417/18723	7.07e-07	3.32e-05	95
GO:00064704	Colorectum	FAP	protein dephosphorylation	69/2622	281/18723	1.47e-06	6.39e-05	69
GO:00163114	Colorectum	CRC	dephosphorylation	79/2078	417/18723	1.27e-06	7.21e-05	79
GO:00064705	Colorectum	CRC	protein dephosphorylation	57/2078	281/18723	4.49e-06	1.87e-04	57
GO:001631110	Esophagus	ESCC	dephosphorylation	251/8552	417/18723	1.26e-09	2.99e-08	251
GO:000647018	Esophagus	ESCC	protein dephosphorylation	177/8552	281/18723	3.13e-09	6.72e-08	177
GO:00064707	Lung	IAC	protein dephosphorylation	60/2061	281/18723	3.24e-07	2.48e-05	60
GO:00163116	Lung	IAC	dephosphorylation	75/2061	417/18723	1.21e-05	3.64e-04	75
GO:000647012	Lung	AIS	protein dephosphorylation	56/1849	281/18723	2.47e-07	2.24e-05	56
GO:001631112	Lung	AIS	dephosphorylation	69/1849	417/18723	1.27e-05	4.78e-04	69
GO:000647015	Oral cavity	OSCC	protein dephosphorylation	162/7305	281/18723	1.56e-10	4.56e-09	162
GO:00163119	Oral cavity	OSCC	dephosphorylation	220/7305	417/18723	6.33e-09	1.34e-07	220

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0415121	Lung	AIS	PI3K-Akt signaling pathway	57/961	354/8465	3.72e-03	2.00e-02	1.28e-02	57
hsa0516531	Lung	AIS	Human papillomavirus infection	64/961	331/8465	1.03e-05	3.04e-04	1.95e-04	64
hsa0407131	Lung	AIS	Sphingolipid signaling pathway	25/961	121/8465	2.03e-03	1.29e-02	8.24e-03	25
hsa0415131	Lung	AIS	PI3K-Akt signaling pathway	57/961	354/8465	3.72e-03	2.00e-02	1.28e-02	57
hsa030158	Oral cavity	OSCC	mRNA surveillance pathway	75/3704	97/8465	1.30e-11	2.01e-10	1.02e-10	75
hsa051659	Oral cavity	OSCC	Human papillomavirus infection	200/3704	331/8465	3.83e-10	4.93e-09	2.51e-09	200
hsa0407114	Oral cavity	OSCC	Sphingolipid signaling pathway	82/3704	121/8465	6.97e-08	5.08e-07	2.58e-07	82
hsa041516	Oral cavity	OSCC	PI3K-Akt signaling pathway	185/3704	354/8465	6.26e-04	1.86e-03	9.49e-04	185
hsa041529	Oral cavity	OSCC	AMPK signaling pathway	71/3704	121/8465	6.29e-04	1.86e-03	9.49e-04	71
hsa0301513	Oral cavity	OSCC	mRNA surveillance pathway	75/3704	97/8465	1.30e-11	2.01e-10	1.02e-10	75
hsa0516514	Oral cavity	OSCC	Human papillomavirus infection	200/3704	331/8465	3.83e-10	4.93e-09	2.51e-09	200
hsa0407115	Oral cavity	OSCC	Sphingolipid signaling pathway	82/3704	121/8465	6.97e-08	5.08e-07	2.58e-07	82
hsa0415113	Oral cavity	OSCC	PI3K-Akt signaling pathway	185/3704	354/8465	6.26e-04	1.86e-03	9.49e-04	185
hsa0415212	Oral cavity	OSCC	AMPK signaling pathway	71/3704	121/8465	6.29e-04	1.86e-03	9.49e-04	71

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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

PPP2R3A

SNV

Missense_Mutation

novel

c.2108N>T

p.Ala703Val

p.A703V

Q06190

protein_coding

tolerated(0.19)

benign(0)

TCGA-3C-AALI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Poly E

Complete Response

PPP2R3A

SNV

Missense_Mutation

rs369517042

c.1703C>T

p.Ser568Leu

p.S568L

Q06190

protein_coding

tolerated_low_confidence(0.2)

benign(0.005)

TCGA-A2-A0EY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

PPP2R3A

SNV

Missense_Mutation

c.3229G>C

p.Glu1077Gln

p.E1077Q

Q06190

protein_coding

deleterious(0.02)

benign(0.366)

TCGA-A8-A09G-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

PPP2R3A

SNV

Missense_Mutation

novel

c.1045N>G

p.Gln349Glu

p.Q349E

Q06190

protein_coding

tolerated_low_confidence(0.43)

benign(0)

TCGA-AC-A6IW-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PPP2R3A

SNV

Missense_Mutation

novel

c.508N>G

p.Asn170Asp

p.N170D

Q06190

protein_coding

deleterious_low_confidence(0)

benign(0.054)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PPP2R3A

SNV

Missense_Mutation

c.2027N>T

p.Thr676Ile

p.T676I

Q06190

protein_coding

deleterious(0.04)

probably_damaging(0.933)

TCGA-E2-A14W-01

Breast

breast invasive carcinoma

Male

>=65

I/II

Chemotherapy

cytoxan

PPP2R3A

SNV

Missense_Mutation

novel

c.2197N>C

p.Glu733Gln

p.E733Q

Q06190

protein_coding

deleterious(0.02)

possibly_damaging(0.733)

TCGA-MY-A5BF-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

PPP2R3A

SNV

Missense_Mutation

rs775142377

c.3165C>G

p.Phe1055Leu

p.F1055L

Q06190

protein_coding

tolerated(0.24)

possibly_damaging(0.749)

TCGA-Q1-A73O-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

PPP2R3A

SNV

Missense_Mutation

rs376094878

c.1184N>T

p.Ser395Leu

p.S395L

Q06190

protein_coding

tolerated_low_confidence(0.17)

benign(0.057)

TCGA-VS-A8EB-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

PPP2R3A

SNV

Missense_Mutation

novel

c.1863N>C

p.Met621Ile

p.M621I

Q06190

protein_coding

deleterious(0.01)

benign(0.021)

TCGA-VS-A9UP-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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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