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: PMEPA1

Gene summary for PMEPA1

Gene summary.

Gene information	Species	Human
	Gene symbol	PMEPA1
	Gene ID	56937
	Gene name	prostate transmembrane protein, androgen induced 1
	Gene Alias	STAG1
	Cytomap	20q13.31
	Gene Type	protein-coding
	GO ID	GO:0001932
	UniProtAcc	Q969W9

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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
56937	PMEPA1	GSM4909285	Human	Breast	IDC	3.49e-07	2.94e-01	0.21
56937	PMEPA1	GSM4909290	Human	Breast	IDC	1.02e-12	4.83e-01	0.2096
56937	PMEPA1	GSM4909295	Human	Breast	IDC	1.39e-06	4.97e-01	0.0898
56937	PMEPA1	GSM4909308	Human	Breast	IDC	8.81e-03	9.07e-02	0.158
56937	PMEPA1	GSM4909311	Human	Breast	IDC	9.12e-03	-1.25e-01	0.1534
56937	PMEPA1	GSM4909317	Human	Breast	IDC	3.19e-23	6.12e-01	0.1355
56937	PMEPA1	GSM4909319	Human	Breast	IDC	7.28e-08	-1.25e-01	0.1563
56937	PMEPA1	GSM4909321	Human	Breast	IDC	1.24e-03	-1.01e-01	0.1559
56937	PMEPA1	brca2	Human	Breast	Precancer	5.65e-07	2.95e-01	-0.024
56937	PMEPA1	DCIS2	Human	Breast	DCIS	1.78e-57	5.27e-01	0.0085
56937	PMEPA1	HTA11_3410_2000001011	Human	Colorectum	AD	5.43e-03	3.42e-01	0.0155
56937	PMEPA1	HTA11_1938_2000001011	Human	Colorectum	AD	1.15e-09	1.18e+00	-0.0811
56937	PMEPA1	HTA11_866_3004761011	Human	Colorectum	AD	1.67e-20	8.11e-01	0.096
56937	PMEPA1	HTA11_7696_3000711011	Human	Colorectum	AD	2.89e-17	7.45e-01	0.0674
56937	PMEPA1	HTA11_6818_2000001011	Human	Colorectum	AD	8.33e-12	1.10e+00	0.0112
56937	PMEPA1	HTA11_6818_2000001021	Human	Colorectum	AD	2.95e-35	1.78e+00	0.0588
56937	PMEPA1	HTA11_99999965104_69814	Human	Colorectum	MSS	1.42e-08	5.97e-01	0.281
56937	PMEPA1	HTA11_99999971662_82457	Human	Colorectum	MSS	4.75e-48	1.55e+00	0.3859
56937	PMEPA1	HTA11_99999973899_84307	Human	Colorectum	MSS	7.32e-53	2.99e+00	0.2585
56937	PMEPA1	HTA11_99999974143_84620	Human	Colorectum	MSS	2.14e-36	1.14e+00	0.3005

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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
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:00485459	Breast	Precancer	response to steroid hormone	53/1080	339/18723	3.07e-11	3.66e-09	53
GO:00432549	Breast	Precancer	regulation of protein-containing complex assembly	50/1080	428/18723	1.63e-06	5.97e-05	50
GO:00713838	Breast	Precancer	cellular response to steroid hormone stimulus	28/1080	204/18723	1.78e-05	4.26e-04	28
GO:00305217	Breast	Precancer	androgen receptor signaling pathway	10/1080	44/18723	1.61e-04	2.69e-03	10
GO:00305187	Breast	Precancer	intracellular steroid hormone receptor signaling pathway	16/1080	116/18723	1.01e-03	1.13e-02	16
GO:00313338	Breast	Precancer	negative regulation of protein-containing complex assembly	18/1080	141/18723	1.27e-03	1.35e-02	18
GO:00305228	Breast	Precancer	intracellular receptor signaling pathway	27/1080	265/18723	2.99e-03	2.57e-02	27
GO:00434018	Breast	Precancer	steroid hormone mediated signaling pathway	16/1080	136/18723	5.21e-03	3.88e-02	16
GO:004854514	Breast	IDC	response to steroid hormone	70/1434	339/18723	1.34e-14	4.23e-12	70
GO:004325414	Breast	IDC	regulation of protein-containing complex assembly	61/1434	428/18723	1.77e-06	7.31e-05	61
GO:007138314	Breast	IDC	cellular response to steroid hormone stimulus	35/1434	204/18723	5.29e-06	1.75e-04	35
GO:003051813	Breast	IDC	intracellular steroid hormone receptor signaling pathway	22/1434	116/18723	6.16e-05	1.28e-03	22
GO:003052113	Breast	IDC	androgen receptor signaling pathway	12/1434	44/18723	8.17e-05	1.60e-03	12
GO:003052214	Breast	IDC	intracellular receptor signaling pathway	37/1434	265/18723	2.77e-04	4.26e-03	37
GO:004340113	Breast	IDC	steroid hormone mediated signaling pathway	22/1434	136/18723	6.51e-04	8.04e-03	22
GO:00459369	Breast	IDC	negative regulation of phosphate metabolic process	53/1434	441/18723	7.21e-04	8.79e-03	53
GO:00105639	Breast	IDC	negative regulation of phosphorus metabolic process	53/1434	442/18723	7.60e-04	9.25e-03	53
GO:003133313	Breast	IDC	negative regulation of protein-containing complex assembly	22/1434	141/18723	1.07e-03	1.17e-02	22
GO:004854524	Breast	DCIS	response to steroid hormone	67/1390	339/18723	1.02e-13	2.76e-11	67
GO:004325424	Breast	DCIS	regulation of protein-containing complex assembly	61/1390	428/18723	6.32e-07	2.71e-05	61

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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

PMEPA1

SNV

Missense_Mutation

c.286N>C

p.Glu96Gln

p.E96Q

Q969W9

protein_coding

tolerated(0.08)

possibly_damaging(0.447)

TCGA-A8-A09K-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PMEPA1

SNV

Missense_Mutation

c.70T>C

p.Cys24Arg

p.C24R

Q969W9

protein_coding

deleterious_low_confidence(0.04)

benign(0.056)

TCGA-C8-A8HQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PMEPA1

SNV

Missense_Mutation

novel

c.789N>A

p.His263Gln

p.H263Q

Q969W9

protein_coding

tolerated_low_confidence(0.34)

benign(0.003)

TCGA-EW-A3U0-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

PMEPA1

insertion

Frame_Shift_Ins

rs751873496

c.624dupC

p.Ser209GlnfsTer3

p.S209Qfs*3

Q969W9

protein_coding

TCGA-AN-A0FV-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PMEPA1

SNV

Missense_Mutation

c.837N>T

p.Lys279Asn

p.K279N

Q969W9

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.997)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

PMEPA1

SNV

Missense_Mutation

rs761429643

c.353N>A

p.Arg118His

p.R118H

Q969W9

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

PMEPA1

insertion

Frame_Shift_Ins

novel

c.331_332insGAGGA

p.Ala111GlyfsTer70

p.A111Gfs*70

Q969W9

protein_coding

TCGA-DS-A1OB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

carboplatin

PMEPA1

SNV

Missense_Mutation

c.70N>A

p.Cys24Ser

p.C24S

Q969W9

protein_coding

deleterious_low_confidence(0.01)

benign(0)

TCGA-A6-2680-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

PMEPA1

SNV

Missense_Mutation

c.43N>A

p.Ala15Thr

p.A15T

Q969W9

protein_coding

tolerated_low_confidence(0.2)

benign(0.009)

TCGA-AM-5821-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

PMEPA1

SNV

Missense_Mutation

novel

c.167N>C

p.Val56Ala

p.V56A

Q969W9

protein_coding

deleterious(0.05)

benign(0.266)

TCGA-CK-4951-01

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

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