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: PPP1R10

Gene summary for PPP1R10

Gene summary.

Gene information	Species	Human
	Gene symbol	PPP1R10
	Gene ID	5514
	Gene name	protein phosphatase 1 regulatory subunit 10
	Gene Alias	CAT53
	Cytomap	6p21.33
	Gene Type	protein-coding
	GO ID	GO:0000075
	UniProtAcc	Q2L6I0

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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
5514	PPP1R10	AEH-subject1	Human	Endometrium	AEH	1.50e-29	5.66e-01	-0.3059
5514	PPP1R10	AEH-subject2	Human	Endometrium	AEH	2.06e-05	2.42e-01	-0.2525
5514	PPP1R10	AEH-subject3	Human	Endometrium	AEH	2.46e-07	2.72e-01	-0.2576
5514	PPP1R10	AEH-subject4	Human	Endometrium	AEH	6.11e-03	1.89e-01	-0.2657
5514	PPP1R10	EEC-subject1	Human	Endometrium	EEC	9.04e-05	2.18e-01	-0.2682
5514	PPP1R10	EEC-subject3	Human	Endometrium	EEC	2.17e-08	-6.64e-02	-0.2525
5514	PPP1R10	EEC-subject4	Human	Endometrium	EEC	7.27e-04	1.91e-01	-0.2571
5514	PPP1R10	GSM5276934	Human	Endometrium	EEC	7.25e-21	5.61e-01	-0.0913
5514	PPP1R10	GSM5276937	Human	Endometrium	EEC	2.95e-13	4.91e-01	-0.0897
5514	PPP1R10	GSM6177620_NYU_UCEC1_lib1_lib1	Human	Endometrium	EEC	1.86e-12	-3.58e-01	-0.1869
5514	PPP1R10	GSM6177620_NYU_UCEC1_lib2_lib2	Human	Endometrium	EEC	2.31e-13	-4.09e-01	-0.1875
5514	PPP1R10	GSM6177620_NYU_UCEC1_lib3_lib3	Human	Endometrium	EEC	7.34e-13	-3.66e-01	-0.1883
5514	PPP1R10	GSM6177621_NYU_UCEC2_lib1_lib1	Human	Endometrium	EEC	1.11e-18	-2.31e-01	-0.1934
5514	PPP1R10	GSM6177622_NYU_UCEC3_lib1_lib1	Human	Endometrium	EEC	1.12e-23	-2.23e-01	-0.1917
5514	PPP1R10	GSM6177622_NYU_UCEC3_lib2_lib2	Human	Endometrium	EEC	3.85e-21	-1.34e-01	-0.1916
5514	PPP1R10	LZE2D	Human	Esophagus	HGIN	4.26e-02	7.52e-02	0.0642
5514	PPP1R10	LZE4T	Human	Esophagus	ESCC	1.32e-12	5.96e-01	0.0811
5514	PPP1R10	LZE5T	Human	Esophagus	ESCC	6.93e-07	4.48e-01	0.0514
5514	PPP1R10	LZE7T	Human	Esophagus	ESCC	1.15e-07	7.94e-01	0.0667
5514	PPP1R10	LZE8T	Human	Esophagus	ESCC	1.31e-08	5.57e-01	0.067

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
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
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
Prostate		BPH: Benign Prostatic Hyperplasia
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:007259410	Endometrium	AEH	establishment of protein localization to organelle	89/2100	422/18723	2.41e-09	1.90e-07	89
GO:200125210	Endometrium	AEH	positive regulation of chromosome organization	25/2100	82/18723	1.95e-06	5.93e-05	25
GO:00345049	Endometrium	AEH	protein localization to nucleus	57/2100	290/18723	1.65e-05	3.42e-04	57
GO:00322069	Endometrium	AEH	positive regulation of telomere maintenance	16/2100	52/18723	1.18e-04	1.66e-03	16
GO:00457877	Endometrium	AEH	positive regulation of cell cycle	56/2100	313/18723	2.73e-04	3.14e-03	56
GO:000691310	Endometrium	AEH	nucleocytoplasmic transport	54/2100	301/18723	3.24e-04	3.62e-03	54
GO:005116910	Endometrium	AEH	nuclear transport	54/2100	301/18723	3.24e-04	3.62e-03	54
GO:000072310	Endometrium	AEH	telomere maintenance	28/2100	131/18723	5.62e-04	5.62e-03	28
GO:00330446	Endometrium	AEH	regulation of chromosome organization	36/2100	187/18723	8.27e-04	7.73e-03	36
GO:00322048	Endometrium	AEH	regulation of telomere maintenance	19/2100	80/18723	1.12e-03	9.78e-03	19
GO:200102010	Endometrium	AEH	regulation of response to DNA damage stimulus	40/2100	219/18723	1.28e-03	1.09e-02	40
GO:00170389	Endometrium	AEH	protein import	37/2100	206/18723	2.56e-03	1.89e-02	37
GO:00900686	Endometrium	AEH	positive regulation of cell cycle process	41/2100	236/18723	2.94e-03	2.09e-02	41
GO:00510549	Endometrium	AEH	positive regulation of DNA metabolic process	36/2100	201/18723	3.05e-03	2.16e-02	36
GO:00459317	Endometrium	AEH	positive regulation of mitotic cell cycle	23/2100	121/18723	7.76e-03	4.33e-02	23
GO:007259415	Endometrium	EEC	establishment of protein localization to organelle	94/2168	422/18723	2.22e-10	2.51e-08	94
GO:200125213	Endometrium	EEC	positive regulation of chromosome organization	26/2168	82/18723	9.70e-07	3.31e-05	26
GO:003450413	Endometrium	EEC	protein localization to nucleus	60/2168	290/18723	5.09e-06	1.26e-04	60
GO:000691314	Endometrium	EEC	nucleocytoplasmic transport	59/2168	301/18723	3.31e-05	5.65e-04	59
GO:005116914	Endometrium	EEC	nuclear transport	59/2168	301/18723	3.31e-05	5.65e-04	59

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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

PPP1R10

SNV

Missense_Mutation

novel

c.2333N>A

p.Gly778Glu

p.G778E

Q96QC0

protein_coding

tolerated_low_confidence(0.06)

benign(0.017)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

PPP1R10

SNV

Missense_Mutation

novel

c.1669G>A

p.Val557Ile

p.V557I

Q96QC0

protein_coding

tolerated(0.21)

probably_damaging(0.967)

TCGA-E2-A150-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

PPP1R10

SNV

Missense_Mutation

novel

c.2368N>C

p.Ser790Arg

p.S790R

Q96QC0

protein_coding

tolerated_low_confidence(0.1)

benign(0.003)

TCGA-LL-A5YN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

PPP1R10

insertion

Frame_Shift_Ins

novel

c.1483_1484insT

p.Gln495LeufsTer12

p.Q495Lfs*12

Q96QC0

protein_coding

TCGA-3C-AALI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Poly E

Complete Response

PPP1R10

insertion

Nonsense_Mutation

novel

c.2107_2108insGAGGTTAGAACTGACTACAAAGACACAGGAA

p.Tyr703Ter

p.Y703*

Q96QC0

protein_coding

TCGA-AQ-A54N-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PPP1R10

SNV

Missense_Mutation

rs748839668

c.2764C>T

p.Arg922Cys

p.R922C

Q96QC0

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.984)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

PPP1R10

SNV

Missense_Mutation

rs774652564

c.2345G>A

p.Arg782His

p.R782H

Q96QC0

protein_coding

deleterious_low_confidence(0.01)

benign(0.12)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

PPP1R10

SNV

Missense_Mutation

rs767544705

c.1343G>A

p.Arg448Gln

p.R448Q

Q96QC0

protein_coding

deleterious(0.01)

probably_damaging(0.988)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

PPP1R10

SNV

Missense_Mutation

rs747071643

c.2255N>A

p.Arg752His

p.R752H

Q96QC0

protein_coding

tolerated_low_confidence(0.08)

benign(0.057)

TCGA-DR-A0ZL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

PPP1R10

SNV

Missense_Mutation

novel

c.249N>C

p.Lys83Asn

p.K83N

Q96QC0

protein_coding

deleterious(0.02)

possibly_damaging(0.863)

TCGA-IR-A3LH-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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