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: PEA15

Gene summary for PEA15

Gene summary.

Gene information	Species	Human
	Gene symbol	PEA15
	Gene ID	8682
	Gene name	proliferation and apoptosis adaptor protein 15
	Gene Alias	HMAT1
	Cytomap	1q23.2
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	Q15121

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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
8682	PEA15	AEH-subject3	Human	Endometrium	AEH	3.09e-02	-1.28e-01	-0.2576
8682	PEA15	EEC-subject1	Human	Endometrium	EEC	3.97e-02	-8.14e-02	-0.2682
8682	PEA15	EEC-subject3	Human	Endometrium	EEC	1.19e-09	1.06e-01	-0.2525
8682	PEA15	GSM5276934	Human	Endometrium	EEC	5.55e-30	6.73e-01	-0.0913
8682	PEA15	GSM5276937	Human	Endometrium	EEC	1.31e-14	5.50e-01	-0.0897
8682	PEA15	GSM6177620_NYU_UCEC1_lib1_lib1	Human	Endometrium	EEC	1.98e-17	1.38e-01	-0.1869
8682	PEA15	GSM6177620_NYU_UCEC1_lib2_lib2	Human	Endometrium	EEC	1.87e-21	9.87e-02	-0.1875
8682	PEA15	GSM6177620_NYU_UCEC1_lib3_lib3	Human	Endometrium	EEC	3.31e-20	4.31e-02	-0.1883
8682	PEA15	GSM6177621_NYU_UCEC2_lib1_lib1	Human	Endometrium	EEC	2.31e-21	4.25e-01	-0.1934
8682	PEA15	GSM6177622_NYU_UCEC3_lib1_lib1	Human	Endometrium	EEC	9.01e-16	3.94e-02	-0.1917
8682	PEA15	GSM6177622_NYU_UCEC3_lib2_lib2	Human	Endometrium	EEC	2.39e-21	-3.98e-03	-0.1916
8682	PEA15	LZE4T	Human	Esophagus	ESCC	3.39e-14	6.72e-02	0.0811
8682	PEA15	LZE7T	Human	Esophagus	ESCC	1.87e-04	1.05e-01	0.0667
8682	PEA15	LZE8T	Human	Esophagus	ESCC	1.35e-06	-1.60e-01	0.067
8682	PEA15	LZE20T	Human	Esophagus	ESCC	2.94e-15	-1.85e-01	0.0662
8682	PEA15	LZE21D1	Human	Esophagus	HGIN	2.36e-03	-1.90e-01	0.0632
8682	PEA15	LZE22D1	Human	Esophagus	HGIN	1.27e-05	-1.78e-01	0.0595
8682	PEA15	LZE6T	Human	Esophagus	ESCC	9.85e-06	5.48e-02	0.0845
8682	PEA15	P1T-E	Human	Esophagus	ESCC	1.26e-04	2.10e-01	0.0875
8682	PEA15	P2T-E	Human	Esophagus	ESCC	4.30e-22	5.64e-01	0.1177

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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
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
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:200123316	Endometrium	AEH	regulation of apoptotic signaling pathway	86/2100	356/18723	2.97e-12	4.95e-10	86
GO:20012358	Endometrium	AEH	positive regulation of apoptotic signaling pathway	36/2100	126/18723	7.56e-08	3.92e-06	36
GO:009719116	Endometrium	AEH	extrinsic apoptotic signaling pathway	49/2100	219/18723	1.58e-06	4.94e-05	49
GO:200123416	Endometrium	AEH	negative regulation of apoptotic signaling pathway	49/2100	224/18723	3.12e-06	8.58e-05	49
GO:200123616	Endometrium	AEH	regulation of extrinsic apoptotic signaling pathway	37/2100	151/18723	3.17e-06	8.69e-05	37
GO:00510515	Endometrium	AEH	negative regulation of transport	79/2100	470/18723	1.51e-04	1.99e-03	79
GO:20012387	Endometrium	AEH	positive regulation of extrinsic apoptotic signaling pathway	15/2100	48/18723	1.58e-04	2.08e-03	15
GO:19020434	Endometrium	AEH	positive regulation of extrinsic apoptotic signaling pathway via death domain receptors	7/2100	13/18723	2.05e-04	2.54e-03	7
GO:200123716	Endometrium	AEH	negative regulation of extrinsic apoptotic signaling pathway	23/2100	97/18723	3.66e-04	3.99e-03	23
GO:000862510	Endometrium	AEH	extrinsic apoptotic signaling pathway via death domain receptors	19/2100	82/18723	1.54e-03	1.26e-02	19
GO:19020419	Endometrium	AEH	regulation of extrinsic apoptotic signaling pathway via death domain receptors	13/2100	49/18723	2.31e-03	1.74e-02	13
GO:0034763	Endometrium	AEH	negative regulation of transmembrane transport	26/2100	143/18723	8.78e-03	4.78e-02	26
GO:200123317	Endometrium	EEC	regulation of apoptotic signaling pathway	91/2168	356/18723	1.31e-13	3.28e-11	91
GO:200123516	Endometrium	EEC	positive regulation of apoptotic signaling pathway	37/2168	126/18723	5.23e-08	2.83e-06	37
GO:200123417	Endometrium	EEC	negative regulation of apoptotic signaling pathway	53/2168	224/18723	2.53e-07	1.09e-05	53
GO:009719117	Endometrium	EEC	extrinsic apoptotic signaling pathway	52/2168	219/18723	2.91e-07	1.20e-05	52
GO:200123617	Endometrium	EEC	regulation of extrinsic apoptotic signaling pathway	40/2168	151/18723	3.33e-07	1.33e-05	40
GO:200123814	Endometrium	EEC	positive regulation of extrinsic apoptotic signaling pathway	16/2168	48/18723	5.88e-05	9.12e-04	16
GO:200123717	Endometrium	EEC	negative regulation of extrinsic apoptotic signaling pathway	25/2168	97/18723	8.28e-05	1.19e-03	25
GO:190204312	Endometrium	EEC	positive regulation of extrinsic apoptotic signaling pathway via death domain receptors	7/2168	13/18723	2.51e-04	2.92e-03	7

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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

PEA15

SNV

Missense_Mutation

novel

c.418G>A

p.Glu140Lys

p.E140K

Q15121

protein_coding

deleterious(0.02)

benign(0.242)

TCGA-PE-A5DE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

PEA15

SNV

Missense_Mutation

novel

c.436C>T

p.Pro146Ser

p.P146S

Q15121

protein_coding

tolerated(0.05)

benign(0.023)

TCGA-C5-A902-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

PEA15

SNV

Missense_Mutation

novel

c.137C>T

p.Ser46Leu

p.S46L

Q15121

protein_coding

tolerated(0.06)

probably_damaging(0.992)

TCGA-AJ-A3NE-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

PEA15

SNV

Missense_Mutation

c.365N>A

p.Arg122His

p.R122H

Q15121

protein_coding

tolerated(0.11)

probably_damaging(0.978)

TCGA-AP-A0LM-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

PEA15

SNV

Missense_Mutation

novel

c.194N>T

p.Ala65Val

p.A65V

Q15121

protein_coding

tolerated(0.19)

benign(0.261)

TCGA-AX-A06F-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatin

PEA15

SNV

Missense_Mutation

novel

c.52N>G

p.Thr18Ala

p.T18A

Q15121

protein_coding

tolerated_low_confidence(0.81)

benign(0)

TCGA-AX-A1C4-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

PEA15

SNV

Missense_Mutation

novel

c.155N>C

p.Ile52Thr

p.I52T

Q15121

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AX-A2HJ-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

PEA15

SNV

Missense_Mutation

novel

c.340G>A

p.Asp114Asn

p.D114N

Q15121

protein_coding

deleterious(0)

benign(0.161)

TCGA-B5-A11E-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

PEA15

SNV

Missense_Mutation

novel

c.392A>G

p.Asp131Gly

p.D131G

Q15121

protein_coding

tolerated(0.09)

probably_damaging(0.926)

TCGA-B5-A3FC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

PEA15

SNV

Missense_Mutation

c.400N>T

p.Arg134Trp

p.R134W

Q15121

protein_coding

deleterious(0)

probably_damaging(0.993)

TCGA-D1-A103-01

Endometrium

uterine corpus endometrioid carcinoma

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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