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: PPP3CC

Gene summary for PPP3CC

Gene summary.

Gene information	Species	Human
	Gene symbol	PPP3CC
	Gene ID	5533
	Gene name	protein phosphatase 3 catalytic subunit gamma
	Gene Alias	CALNA3
	Cytomap	8p21.3
	Gene Type	protein-coding
	GO ID	GO:0006464
	UniProtAcc	P48454

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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
5533	PPP3CC	LZE4T	Human	Esophagus	ESCC	3.80e-08	2.54e-01	0.0811
5533	PPP3CC	LZE24T	Human	Esophagus	ESCC	4.71e-08	2.70e-01	0.0596
5533	PPP3CC	P1T-E	Human	Esophagus	ESCC	2.02e-07	3.11e-01	0.0875
5533	PPP3CC	P2T-E	Human	Esophagus	ESCC	5.66e-23	3.70e-01	0.1177
5533	PPP3CC	P4T-E	Human	Esophagus	ESCC	9.30e-18	3.89e-01	0.1323
5533	PPP3CC	P5T-E	Human	Esophagus	ESCC	4.42e-09	1.25e-01	0.1327
5533	PPP3CC	P8T-E	Human	Esophagus	ESCC	2.42e-20	3.60e-01	0.0889
5533	PPP3CC	P9T-E	Human	Esophagus	ESCC	6.24e-09	2.24e-01	0.1131
5533	PPP3CC	P10T-E	Human	Esophagus	ESCC	1.25e-18	2.24e-01	0.116
5533	PPP3CC	P11T-E	Human	Esophagus	ESCC	4.03e-12	4.24e-01	0.1426
5533	PPP3CC	P12T-E	Human	Esophagus	ESCC	6.53e-13	2.37e-01	0.1122
5533	PPP3CC	P15T-E	Human	Esophagus	ESCC	3.40e-02	8.68e-02	0.1149
5533	PPP3CC	P16T-E	Human	Esophagus	ESCC	6.44e-08	1.20e-01	0.1153
5533	PPP3CC	P19T-E	Human	Esophagus	ESCC	2.55e-08	5.44e-01	0.1662
5533	PPP3CC	P20T-E	Human	Esophagus	ESCC	1.63e-19	4.05e-01	0.1124
5533	PPP3CC	P21T-E	Human	Esophagus	ESCC	8.13e-07	1.58e-01	0.1617
5533	PPP3CC	P22T-E	Human	Esophagus	ESCC	5.45e-07	1.72e-01	0.1236
5533	PPP3CC	P23T-E	Human	Esophagus	ESCC	1.13e-09	2.90e-01	0.108
5533	PPP3CC	P24T-E	Human	Esophagus	ESCC	1.50e-18	3.77e-01	0.1287
5533	PPP3CC	P26T-E	Human	Esophagus	ESCC	2.35e-31	5.39e-01	0.1276

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
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: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:003010018	Esophagus	ESCC	regulation of endocytosis	135/8552	211/18723	5.75e-08	1.02e-06	135
GO:004580718	Esophagus	ESCC	positive regulation of endocytosis	69/8552	100/18723	1.97e-06	2.29e-05	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
GO:003010016	Oral cavity	OSCC	regulation of endocytosis	121/7305	211/18723	4.74e-08	8.80e-07	121
GO:004580710	Oral cavity	OSCC	positive regulation of endocytosis	59/7305	100/18723	3.99e-05	3.48e-04	59
GO:1903421	Oral cavity	OSCC	regulation of synaptic vesicle recycling	18/7305	27/18723	3.34e-03	1.42e-02	18
GO:00331733	Oral cavity	OSCC	calcineurin-NFAT signaling cascade	26/7305	43/18723	3.55e-03	1.49e-02	26
GO:00480164	Oral cavity	OSCC	inositol phosphate-mediated signaling	30/7305	55/18723	1.39e-02	4.59e-02	30
GO:000647023	Oral cavity	EOLP	protein dephosphorylation	72/2218	281/18723	1.19e-10	1.35e-08	72
GO:001631114	Oral cavity	EOLP	dephosphorylation	85/2218	417/18723	3.19e-07	9.47e-06	85
GO:003010023	Oral cavity	EOLP	regulation of endocytosis	51/2218	211/18723	4.24e-07	1.19e-05	51
GO:004580724	Oral cavity	EOLP	positive regulation of endocytosis	27/2218	100/18723	2.69e-05	3.94e-04	27
GO:00990035	Oral cavity	EOLP	vesicle-mediated transport in synapse	39/2218	200/18723	1.14e-03	8.29e-03	39
GO:00995044	Oral cavity	EOLP	synaptic vesicle cycle	34/2218	181/18723	4.25e-03	2.33e-02	34
GO:00484885	Oral cavity	EOLP	synaptic vesicle endocytosis	15/2218	62/18723	5.00e-03	2.64e-02	15
GO:01402385	Oral cavity	EOLP	presynaptic endocytosis	15/2218	62/18723	5.00e-03	2.64e-02	15
GO:003010031	Oral cavity	NEOLP	regulation of endocytosis	47/2005	211/18723	7.96e-07	2.20e-05	47

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0472012	Oral cavity	EOLP	Long-term potentiation	21/1218	67/8465	3.04e-04	1.29e-03	7.62e-04	21
hsa043702	Oral cavity	EOLP	VEGF signaling pathway	19/1218	59/8465	3.96e-04	1.62e-03	9.55e-04	19
hsa041142	Oral cavity	EOLP	Oocyte meiosis	33/1218	131/8465	7.09e-04	2.69e-03	1.59e-03	33
hsa0472812	Oral cavity	EOLP	Dopaminergic synapse	33/1218	132/8465	8.18e-04	3.04e-03	1.79e-03	33
hsa049219	Oral cavity	EOLP	Oxytocin signaling pathway	36/1218	154/8465	1.79e-03	6.08e-03	3.58e-03	36
hsa0431016	Oral cavity	EOLP	Wnt signaling pathway	37/1218	171/8465	6.23e-03	1.83e-02	1.08e-02	37
hsa040224	Oral cavity	EOLP	cGMP-PKG signaling pathway	36/1218	167/8465	7.34e-03	2.12e-02	1.25e-02	36
hsa0436023	Oral cavity	EOLP	Axon guidance	38/1218	182/8465	1.02e-02	2.80e-02	1.65e-02	38
hsa0516754	Oral cavity	EOLP	Kaposi sarcoma-associated herpesvirus infection	68/1218	194/8465	2.59e-13	2.09e-11	1.24e-11	68
hsa0516355	Oral cavity	EOLP	Human cytomegalovirus infection	68/1218	225/8465	5.29e-10	1.90e-08	1.12e-08	68
hsa0465933	Oral cavity	EOLP	Th17 cell differentiation	41/1218	108/8465	9.84e-10	3.18e-08	1.87e-08	41
hsa0517053	Oral cavity	EOLP	Human immunodeficiency virus 1 infection	63/1218	212/8465	4.85e-09	8.71e-08	5.14e-08	63
hsa0501455	Oral cavity	EOLP	Amyotrophic lateral sclerosis	93/1218	364/8465	7.07e-09	1.14e-07	6.74e-08	93
hsa043803	Oral cavity	EOLP	Osteoclast differentiation	44/1218	128/8465	8.92e-09	1.37e-07	8.10e-08	44
hsa0421855	Oral cavity	EOLP	Cellular senescence	50/1218	156/8465	1.27e-08	1.83e-07	1.08e-07	50
hsa0516654	Oral cavity	EOLP	Human T-cell leukemia virus 1 infection	64/1218	222/8465	1.37e-08	1.83e-07	1.08e-07	64
hsa046255	Oral cavity	EOLP	C-type lectin receptor signaling pathway	38/1218	104/8465	1.39e-08	1.83e-07	1.08e-07	38
hsa0541756	Oral cavity	EOLP	Lipid and atherosclerosis	62/1218	215/8465	2.28e-08	2.83e-07	1.67e-07	62
hsa0502255	Oral cavity	EOLP	Pathways of neurodegeneration - multiple diseases	110/1218	476/8465	1.09e-07	1.26e-06	7.40e-07	110
hsa052353	Oral cavity	EOLP	PD-L1 expression and PD-1 checkpoint pathway in cancer	32/1218	89/8465	2.96e-07	3.18e-06	1.88e-06	32

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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

PPP3CC

insertion

Nonsense_Mutation

novel

c.420_421insGCAAATCTAATGAGAAAATAGTGTACTTGTCAC

p.Leu140_Phe141insAlaAsnLeuMetArgLysTerCysThrCysHis

p.L140_F141insANLMRK*CTCH

P48454

protein_coding

TCGA-AN-A04C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PPP3CC

SNV

Missense_Mutation

c.1466G>A

p.Arg489Gln

p.R489Q

P48454

protein_coding

deleterious(0.04)

possibly_damaging(0.579)

TCGA-C5-A2LX-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

PPP3CC

SNV

Missense_Mutation

novel

c.916N>T

p.Asn306Tyr

p.N306Y

P48454

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-C5-A8XI-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

PPP3CC

SNV

Missense_Mutation

novel

c.356N>C

p.Gly119Ala

p.G119A

P48454

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-C5-A8ZZ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unspecific

Cisplatin

PPP3CC

SNV

Missense_Mutation

rs767818391

c.7N>A

p.Gly3Arg

p.G3R

P48454

protein_coding

tolerated_low_confidence(0.2)

benign(0)

TCGA-AA-3947-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

PPP3CC

SNV

Missense_Mutation

rs142268010

c.749N>A

p.Arg250Gln

p.R250Q

P48454

protein_coding

deleterious(0.01)

probably_damaging(0.999)

TCGA-AA-3950-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

PPP3CC

SNV

Missense_Mutation

novel

c.1379C>G

p.Ala460Gly

p.A460G

P48454

protein_coding

tolerated(0.12)

possibly_damaging(0.611)

TCGA-AY-4070-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Chemotherapy

5-fu

PPP3CC

SNV

Missense_Mutation

novel

c.115N>T

p.Val39Phe

p.V39F

P48454

protein_coding

tolerated(0.3)

benign(0.001)

TCGA-CA-6717-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Chemotherapy

oxaliplatin

PPP3CC

SNV

Missense_Mutation

novel

c.4N>C

p.Ser2Pro

p.S2P

P48454

protein_coding

deleterious_low_confidence(0.01)

benign(0)

TCGA-AG-3602-01

Colorectum

rectum adenocarcinoma

Female

>=65

III/IV

Unknown

PPP3CC

SNV

Missense_Mutation

rs558233561

c.1483N>A

p.Ala495Thr

p.A495T

P48454

protein_coding

tolerated(0.52)

benign(0)

TCGA-EI-6510-01

Colorectum

rectum adenocarcinoma

Female

>=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
5533	PPP3CC	TRANSCRIPTION FACTOR		VOCLOSPORIN	VOCLOSPORIN

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