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: PPP2R5D

Gene summary for PPP2R5D

Gene summary.

Gene information	Species	Human
	Gene symbol	PPP2R5D
	Gene ID	5528
	Gene name	protein phosphatase 2 regulatory subunit B'delta
	Gene Alias	B56D
	Cytomap	6p21.1
	Gene Type	protein-coding
	GO ID	GO:0001932
	UniProtAcc	Q14738

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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
5528	PPP2R5D	LZE24T	Human	Esophagus	ESCC	2.68e-07	2.73e-01	0.0596
5528	PPP2R5D	P1T-E	Human	Esophagus	ESCC	5.58e-07	3.08e-01	0.0875
5528	PPP2R5D	P2T-E	Human	Esophagus	ESCC	6.82e-20	3.47e-01	0.1177
5528	PPP2R5D	P4T-E	Human	Esophagus	ESCC	9.24e-10	3.35e-01	0.1323
5528	PPP2R5D	P5T-E	Human	Esophagus	ESCC	1.67e-09	1.40e-01	0.1327
5528	PPP2R5D	P8T-E	Human	Esophagus	ESCC	4.36e-12	1.35e-01	0.0889
5528	PPP2R5D	P9T-E	Human	Esophagus	ESCC	9.55e-06	1.58e-01	0.1131
5528	PPP2R5D	P10T-E	Human	Esophagus	ESCC	1.04e-15	2.74e-01	0.116
5528	PPP2R5D	P11T-E	Human	Esophagus	ESCC	2.01e-07	3.58e-01	0.1426
5528	PPP2R5D	P12T-E	Human	Esophagus	ESCC	5.13e-19	3.57e-01	0.1122
5528	PPP2R5D	P15T-E	Human	Esophagus	ESCC	6.11e-05	2.43e-01	0.1149
5528	PPP2R5D	P16T-E	Human	Esophagus	ESCC	5.62e-13	2.43e-01	0.1153
5528	PPP2R5D	P17T-E	Human	Esophagus	ESCC	9.47e-07	3.72e-01	0.1278
5528	PPP2R5D	P19T-E	Human	Esophagus	ESCC	7.24e-03	6.88e-01	0.1662
5528	PPP2R5D	P20T-E	Human	Esophagus	ESCC	1.63e-09	2.62e-01	0.1124
5528	PPP2R5D	P21T-E	Human	Esophagus	ESCC	2.32e-17	3.82e-01	0.1617
5528	PPP2R5D	P22T-E	Human	Esophagus	ESCC	1.49e-16	3.22e-01	0.1236
5528	PPP2R5D	P23T-E	Human	Esophagus	ESCC	3.15e-19	3.86e-01	0.108
5528	PPP2R5D	P24T-E	Human	Esophagus	ESCC	3.02e-15	3.32e-01	0.1287
5528	PPP2R5D	P26T-E	Human	Esophagus	ESCC	4.25e-12	3.01e-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
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease

∗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:0010563111	Esophagus	ESCC	negative regulation of phosphorus metabolic process	274/8552	442/18723	2.32e-12	9.41e-11	274
GO:0045936111	Esophagus	ESCC	negative regulation of phosphate metabolic process	273/8552	441/18723	3.18e-12	1.25e-10	273
GO:0042326111	Esophagus	ESCC	negative regulation of phosphorylation	237/8552	385/18723	1.86e-10	5.33e-09	237
GO:0001933111	Esophagus	ESCC	negative regulation of protein phosphorylation	213/8552	342/18723	3.54e-10	9.76e-09	213
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:0035304111	Esophagus	ESCC	regulation of protein dephosphorylation	66/8552	90/18723	8.82e-08	1.48e-06	66
GO:0035303111	Esophagus	ESCC	regulation of dephosphorylation	88/8552	128/18723	1.04e-07	1.71e-06	88
GO:00353074	Esophagus	ESCC	positive regulation of protein dephosphorylation	31/8552	45/18723	1.40e-03	6.62e-03	31
GO:00353066	Esophagus	ESCC	positive regulation of dephosphorylation	38/8552	59/18723	2.86e-03	1.21e-02	38
GO:001810710	Esophagus	ESCC	peptidyl-threonine phosphorylation	66/8552	116/18723	9.76e-03	3.37e-02	66
GO:001821010	Esophagus	ESCC	peptidyl-threonine modification	70/8552	125/18723	1.29e-02	4.25e-02	70
GO:001056322	Liver	HCC	negative regulation of phosphorus metabolic process	259/7958	442/18723	4.29e-12	1.92e-10	259
GO:004593622	Liver	HCC	negative regulation of phosphate metabolic process	258/7958	441/18723	6.00e-12	2.60e-10	258
GO:004232622	Liver	HCC	negative regulation of phosphorylation	227/7958	385/18723	3.98e-11	1.52e-09	227
GO:000193322	Liver	HCC	negative regulation of protein phosphorylation	196/7958	342/18723	1.95e-08	4.63e-07	196
GO:001631121	Liver	HCC	dephosphorylation	230/7958	417/18723	1.00e-07	1.96e-06	230
GO:000647021	Liver	HCC	protein dephosphorylation	162/7958	281/18723	1.91e-07	3.46e-06	162
GO:003530412	Liver	HCC	regulation of protein dephosphorylation	62/7958	90/18723	3.66e-07	6.22e-06	62
GO:003530312	Liver	HCC	regulation of dephosphorylation	80/7958	128/18723	3.85e-06	4.98e-05	80

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0411023	Esophagus	ESCC	Cell cycle	126/4205	157/8465	1.34e-15	5.60e-14	2.87e-14	126
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
hsa041146	Esophagus	ESCC	Oocyte meiosis	77/4205	131/8465	2.19e-02	4.80e-02	2.46e-02	77
hsa0411033	Esophagus	ESCC	Cell cycle	126/4205	157/8465	1.34e-15	5.60e-14	2.87e-14	126
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
hsa0411411	Esophagus	ESCC	Oocyte meiosis	77/4205	131/8465	2.19e-02	4.80e-02	2.46e-02	77
hsa041102	Liver	HCC	Cell cycle	106/4020	157/8465	2.54e-07	3.04e-06	1.69e-06	106
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
hsa041103	Liver	HCC	Cell cycle	106/4020	157/8465	2.54e-07	3.04e-06	1.69e-06	106

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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

PPP2R5D

SNV

Missense_Mutation

c.1342C>A

p.Pro448Thr

p.P448T

Q14738

protein_coding

deleterious(0.01)

possibly_damaging(0.853)

TCGA-A8-A07R-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Ancillary

zoledronic

PPP2R5D

SNV

Missense_Mutation

novel

c.1660N>C

p.Glu554Gln

p.E554Q

Q14738

protein_coding

tolerated(0.11)

benign(0.027)

TCGA-AC-A5XS-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

femara

PPP2R5D

SNV

Missense_Mutation

novel

c.1771N>A

p.Ala591Thr

p.A591T

Q14738

protein_coding

tolerated_low_confidence(0.26)

benign(0.031)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

PPP2R5D

SNV

Missense_Mutation

c.423C>G

p.Phe141Leu

p.F141L

Q14738

protein_coding

tolerated(0.52)

benign(0.06)

TCGA-D8-A1JA-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

PPP2R5D

SNV

Missense_Mutation

c.1069C>G

p.Leu357Val

p.L357V

Q14738

protein_coding

deleterious(0.01)

possibly_damaging(0.908)

TCGA-EW-A1PB-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

PPP2R5D

SNV

Missense_Mutation

c.542G>A

p.Arg181Gln

p.R181Q

Q14738

protein_coding

deleterious(0.02)

probably_damaging(1)

TCGA-LL-A8F5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

PPP2R5D

deletion

Frame_Shift_Del

novel

c.1561delN

p.Met521CysfsTer27

p.M521Cfs*27

Q14738

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

PPP2R5D

SNV

Missense_Mutation

novel

c.763C>T

p.Arg255Trp

p.R255W

Q14738

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-EA-A410-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

PPP2R5D

SNV

Missense_Mutation

c.79N>A

p.Asp27Asn

p.D27N

Q14738

protein_coding

tolerated(0.57)

probably_damaging(0.956)

TCGA-EK-A2IP-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

PPP2R5D

SNV

Missense_Mutation

rs769459377

c.1619N>T

p.Thr540Ile

p.T540I

Q14738

protein_coding

tolerated(0.2)

benign(0.065)

TCGA-A6-5661-01

Colorectum

colon 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
5528	PPP2R5D	PROTEIN PHOSPHATASE, ENZYME		cyclophosphamide	CYCLOPHOSPHAMIDE
5528	PPP2R5D	PROTEIN PHOSPHATASE, ENZYME		fluorouracil	FLUOROURACIL
5528	PPP2R5D	PROTEIN PHOSPHATASE, ENZYME		epirubicin	EPIRUBICIN

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