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: PPP2R3C

Gene summary for PPP2R3C

Gene summary.

Gene information	Species	Human
	Gene symbol	PPP2R3C
	Gene ID	55012
	Gene name	protein phosphatase 2 regulatory subunit B''gamma
	Gene Alias	C14orf10
	Cytomap	14q13.2
	Gene Type	protein-coding
	GO ID	GO:0000226
	UniProtAcc	Q969Q6

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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
55012	PPP2R3C	LZE4T	Human	Esophagus	ESCC	7.56e-08	1.41e-01	0.0811
55012	PPP2R3C	LZE7T	Human	Esophagus	ESCC	4.81e-03	1.88e-01	0.0667
55012	PPP2R3C	LZE8T	Human	Esophagus	ESCC	3.18e-05	1.83e-01	0.067
55012	PPP2R3C	LZE24T	Human	Esophagus	ESCC	2.47e-10	2.49e-01	0.0596
55012	PPP2R3C	LZE6T	Human	Esophagus	ESCC	1.53e-06	2.64e-01	0.0845
55012	PPP2R3C	P1T-E	Human	Esophagus	ESCC	5.99e-04	2.52e-01	0.0875
55012	PPP2R3C	P2T-E	Human	Esophagus	ESCC	1.92e-21	3.36e-01	0.1177
55012	PPP2R3C	P4T-E	Human	Esophagus	ESCC	4.03e-20	4.41e-01	0.1323
55012	PPP2R3C	P5T-E	Human	Esophagus	ESCC	2.17e-20	2.84e-01	0.1327
55012	PPP2R3C	P8T-E	Human	Esophagus	ESCC	1.14e-39	7.81e-01	0.0889
55012	PPP2R3C	P9T-E	Human	Esophagus	ESCC	6.91e-11	2.29e-01	0.1131
55012	PPP2R3C	P10T-E	Human	Esophagus	ESCC	5.99e-22	3.84e-01	0.116
55012	PPP2R3C	P11T-E	Human	Esophagus	ESCC	2.55e-15	4.53e-01	0.1426
55012	PPP2R3C	P12T-E	Human	Esophagus	ESCC	3.73e-67	1.13e+00	0.1122
55012	PPP2R3C	P15T-E	Human	Esophagus	ESCC	4.64e-16	2.80e-01	0.1149
55012	PPP2R3C	P16T-E	Human	Esophagus	ESCC	1.31e-07	1.13e-01	0.1153
55012	PPP2R3C	P17T-E	Human	Esophagus	ESCC	5.00e-06	2.68e-01	0.1278
55012	PPP2R3C	P19T-E	Human	Esophagus	ESCC	3.21e-08	4.57e-01	0.1662
55012	PPP2R3C	P20T-E	Human	Esophagus	ESCC	4.95e-13	2.58e-01	0.1124
55012	PPP2R3C	P21T-E	Human	Esophagus	ESCC	2.57e-16	3.03e-01	0.1617

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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
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
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
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:001631110	Esophagus	ESCC	dephosphorylation	251/8552	417/18723	1.26e-09	2.99e-08	251
GO:0035303111	Esophagus	ESCC	regulation of dephosphorylation	88/8552	128/18723	1.04e-07	1.71e-06	88
GO:0048872111	Esophagus	ESCC	homeostasis of number of cells	163/8552	272/18723	1.40e-06	1.69e-05	163
GO:00028318	Esophagus	ESCC	regulation of response to biotic stimulus	191/8552	327/18723	2.12e-06	2.45e-05	191
GO:004586018	Esophagus	ESCC	positive regulation of protein kinase activity	219/8552	386/18723	6.91e-06	6.97e-05	219
GO:003367420	Esophagus	ESCC	positive regulation of kinase activity	260/8552	467/18723	7.26e-06	7.22e-05	260
GO:003086517	Esophagus	ESCC	cortical cytoskeleton organization	44/8552	61/18723	2.50e-05	2.13e-04	44
GO:005188110	Esophagus	ESCC	regulation of mitochondrial membrane potential	51/8552	74/18723	4.42e-05	3.51e-04	51
GO:1903706110	Esophagus	ESCC	regulation of hemopoiesis	201/8552	367/18723	2.60e-04	1.58e-03	201
GO:19021076	Esophagus	ESCC	positive regulation of leukocyte differentiation	93/8552	157/18723	4.20e-04	2.39e-03	93
GO:19037086	Esophagus	ESCC	positive regulation of hemopoiesis	93/8552	157/18723	4.20e-04	2.39e-03	93
GO:19031317	Esophagus	ESCC	mononuclear cell differentiation	226/8552	426/18723	1.20e-03	5.88e-03	226
GO:190210510	Esophagus	ESCC	regulation of leukocyte differentiation	152/8552	279/18723	1.82e-03	8.35e-03	152
GO:00456213	Esophagus	ESCC	positive regulation of lymphocyte differentiation	61/8552	104/18723	5.22e-03	1.97e-02	61
GO:00300984	Esophagus	ESCC	lymphocyte differentiation	192/8552	374/18723	1.52e-02	4.93e-02	192
GO:00308656	Liver	Cirrhotic	cortical cytoskeleton organization	30/4634	61/18723	3.16e-05	3.93e-04	30
GO:001631111	Liver	Cirrhotic	dephosphorylation	130/4634	417/18723	1.58e-03	1.03e-02	130
GO:004887212	Liver	Cirrhotic	homeostasis of number of cells	89/4634	272/18723	1.76e-03	1.12e-02	89
GO:00518815	Liver	Cirrhotic	regulation of mitochondrial membrane potential	30/4634	74/18723	1.97e-03	1.23e-02	30
GO:00028311	Liver	Cirrhotic	regulation of response to biotic stimulus	101/4634	327/18723	6.58e-03	3.25e-02	101

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0516510	Esophagus	ESCC	Human papillomavirus infection	215/4205	331/8465	7.86e-09	7.12e-08	3.65e-08	215
hsa0301524	Esophagus	ESCC	mRNA surveillance pathway	72/4205	97/8465	6.12e-07	4.10e-06	2.10e-06	72
hsa0407116	Esophagus	ESCC	Sphingolipid signaling pathway	85/4205	121/8465	3.04e-06	1.73e-05	8.84e-06	85
hsa0415210	Esophagus	ESCC	AMPK signaling pathway	80/4205	121/8465	1.73e-04	6.67e-04	3.42e-04	80
hsa041517	Esophagus	ESCC	PI3K-Akt signaling pathway	197/4205	354/8465	1.24e-02	2.83e-02	1.45e-02	197
hsa0516515	Esophagus	ESCC	Human papillomavirus infection	215/4205	331/8465	7.86e-09	7.12e-08	3.65e-08	215
hsa0301534	Esophagus	ESCC	mRNA surveillance pathway	72/4205	97/8465	6.12e-07	4.10e-06	2.10e-06	72
hsa0407117	Esophagus	ESCC	Sphingolipid signaling pathway	85/4205	121/8465	3.04e-06	1.73e-05	8.84e-06	85
hsa0415213	Esophagus	ESCC	AMPK signaling pathway	80/4205	121/8465	1.73e-04	6.67e-04	3.42e-04	80
hsa0415114	Esophagus	ESCC	PI3K-Akt signaling pathway	197/4205	354/8465	1.24e-02	2.83e-02	1.45e-02	197
hsa030154	Liver	Cirrhotic	mRNA surveillance pathway	46/2530	97/8465	1.92e-04	1.30e-03	8.03e-04	46
hsa05165	Liver	Cirrhotic	Human papillomavirus infection	124/2530	331/8465	1.55e-03	7.83e-03	4.83e-03	124
hsa0415221	Liver	Cirrhotic	AMPK signaling pathway	49/2530	121/8465	7.90e-03	2.74e-02	1.69e-02	49
hsa0301511	Liver	Cirrhotic	mRNA surveillance pathway	46/2530	97/8465	1.92e-04	1.30e-03	8.03e-04	46
hsa051651	Liver	Cirrhotic	Human papillomavirus infection	124/2530	331/8465	1.55e-03	7.83e-03	4.83e-03	124
hsa0415231	Liver	Cirrhotic	AMPK signaling pathway	49/2530	121/8465	7.90e-03	2.74e-02	1.69e-02	49
hsa0301521	Liver	HCC	mRNA surveillance pathway	66/4020	97/8465	3.16e-05	1.88e-04	1.04e-04	66
hsa0415241	Liver	HCC	AMPK signaling pathway	77/4020	121/8465	2.32e-04	1.11e-03	6.18e-04	77
hsa051652	Liver	HCC	Human papillomavirus infection	188/4020	331/8465	3.34e-04	1.49e-03	8.29e-04	188
hsa040718	Liver	HCC	Sphingolipid signaling pathway	72/4020	121/8465	5.01e-03	1.47e-02	8.18e-03	72

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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

PPP2R3C

SNV

Missense_Mutation

c.455N>G

p.Tyr152Cys

p.Y152C

Q969Q6

protein_coding

deleterious(0.01)

possibly_damaging(0.849)

TCGA-A8-A08P-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

PPP2R3C

SNV

Missense_Mutation

c.521N>T

p.Arg174Ile

p.R174I

Q969Q6

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PPP2R3C

SNV

Missense_Mutation

c.1136N>C

p.Ile379Thr

p.I379T

Q969Q6

protein_coding

tolerated(0.64)

benign(0.018)

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

PPP2R3C

SNV

Missense_Mutation

c.1222N>G

p.Leu408Val

p.L408V

Q969Q6

protein_coding

deleterious(0)

possibly_damaging(0.895)

TCGA-AR-A0TX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PPP2R3C

SNV

Missense_Mutation

c.684N>G

p.Phe228Leu

p.F228L

Q969Q6

protein_coding

deleterious(0.01)

probably_damaging(1)

TCGA-AR-A0TX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PPP2R3C

SNV

Missense_Mutation

c.220T>G

p.Leu74Val

p.L74V

Q969Q6

protein_coding

tolerated(0.15)

possibly_damaging(0.723)

TCGA-C8-A275-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PPP2R3C

SNV

Missense_Mutation

c.605N>A

p.Pro202His

p.P202H

Q969Q6

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-D8-A1Y1-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

tamoxiphen

PPP2R3C

SNV

Missense_Mutation

rs762781414

c.347N>T

p.Ala116Val

p.A116V

Q969Q6

protein_coding

tolerated(0.25)

benign(0.08)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

PPP2R3C

SNV

Missense_Mutation

c.1327G>T

p.Asp443Tyr

p.D443Y

Q969Q6

protein_coding

deleterious(0.02)

possibly_damaging(0.563)

TCGA-C5-A905-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

PPP2R3C

SNV

Missense_Mutation

novel

c.1027N>T

p.Pro343Ser

p.P343S

Q969Q6

protein_coding

deleterious(0.04)

possibly_damaging(0.508)

TCGA-VS-A9UB-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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