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: EPS8

Gene summary for EPS8

Gene summary.

Gene information	Species	Human
	Gene symbol	EPS8
	Gene ID	2059
	Gene name	epidermal growth factor receptor pathway substrate 8
	Gene Alias	DFNB102
	Cytomap	12p12.3
	Gene Type	protein-coding
	GO ID	GO:0000278
	UniProtAcc	B4E3T6

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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
2059	EPS8	P12T-E	Human	Esophagus	ESCC	1.26e-30	6.98e-01	0.1122
2059	EPS8	P15T-E	Human	Esophagus	ESCC	4.99e-37	8.98e-01	0.1149
2059	EPS8	P16T-E	Human	Esophagus	ESCC	6.06e-100	2.42e+00	0.1153
2059	EPS8	P17T-E	Human	Esophagus	ESCC	1.94e-04	2.98e-01	0.1278
2059	EPS8	P19T-E	Human	Esophagus	ESCC	5.20e-05	4.02e-01	0.1662
2059	EPS8	P22T-E	Human	Esophagus	ESCC	1.26e-05	1.95e-01	0.1236
2059	EPS8	P23T-E	Human	Esophagus	ESCC	1.05e-29	8.56e-01	0.108
2059	EPS8	P24T-E	Human	Esophagus	ESCC	3.14e-02	2.34e-01	0.1287
2059	EPS8	P26T-E	Human	Esophagus	ESCC	1.67e-36	8.31e-01	0.1276
2059	EPS8	P27T-E	Human	Esophagus	ESCC	2.36e-45	8.93e-01	0.1055
2059	EPS8	P28T-E	Human	Esophagus	ESCC	2.63e-24	6.07e-01	0.1149
2059	EPS8	P30T-E	Human	Esophagus	ESCC	7.48e-44	1.63e+00	0.137
2059	EPS8	P32T-E	Human	Esophagus	ESCC	1.26e-06	1.90e-01	0.1666
2059	EPS8	P36T-E	Human	Esophagus	ESCC	2.70e-07	2.66e-01	0.1187
2059	EPS8	P37T-E	Human	Esophagus	ESCC	2.03e-16	4.01e-01	0.1371
2059	EPS8	P39T-E	Human	Esophagus	ESCC	7.58e-37	8.33e-01	0.0894
2059	EPS8	P40T-E	Human	Esophagus	ESCC	7.77e-07	2.28e-01	0.109
2059	EPS8	P42T-E	Human	Esophagus	ESCC	1.89e-08	5.30e-01	0.1175
2059	EPS8	P44T-E	Human	Esophagus	ESCC	8.77e-10	3.64e-01	0.1096
2059	EPS8	P47T-E	Human	Esophagus	ESCC	2.24e-08	1.67e-01	0.1067

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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
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:0007015	Colorectum	AD	actin filament organization	167/3918	442/18723	1.65e-16	7.94e-14	167
GO:0032535	Colorectum	AD	regulation of cellular component size	142/3918	383/18723	1.74e-13	3.41e-11	142
GO:1902903	Colorectum	AD	regulation of supramolecular fiber organization	139/3918	383/18723	2.01e-12	3.19e-10	139
GO:0032970	Colorectum	AD	regulation of actin filament-based process	142/3918	397/18723	4.05e-12	5.90e-10	142
GO:0110053	Colorectum	AD	regulation of actin filament organization	108/3918	278/18723	5.02e-12	6.98e-10	108
GO:0008154	Colorectum	AD	actin polymerization or depolymerization	90/3918	218/18723	6.14e-12	8.23e-10	90
GO:0032271	Colorectum	AD	regulation of protein polymerization	94/3918	233/18723	1.01e-11	1.29e-09	94
GO:0030041	Colorectum	AD	actin filament polymerization	81/3918	191/18723	1.35e-11	1.69e-09	81
GO:0051258	Colorectum	AD	protein polymerization	112/3918	297/18723	1.85e-11	2.27e-09	112
GO:0043254	Colorectum	AD	regulation of protein-containing complex assembly	148/3918	428/18723	2.64e-11	3.18e-09	148
GO:0008064	Colorectum	AD	regulation of actin polymerization or depolymerization	79/3918	188/18723	4.17e-11	4.74e-09	79
GO:0030833	Colorectum	AD	regulation of actin filament polymerization	74/3918	172/18723	4.50e-11	5.03e-09	74
GO:0030832	Colorectum	AD	regulation of actin filament length	79/3918	189/18723	5.71e-11	6.27e-09	79
GO:0032956	Colorectum	AD	regulation of actin cytoskeleton organization	127/3918	358/18723	1.03e-10	1.04e-08	127
GO:0022411	Colorectum	AD	cellular component disassembly	147/3918	443/18723	8.53e-10	6.76e-08	147
GO:0022604	Colorectum	AD	regulation of cell morphogenesis	109/3918	309/18723	3.08e-09	2.07e-07	109
GO:0032984	Colorectum	AD	protein-containing complex disassembly	81/3918	224/18723	9.41e-08	4.65e-06	81
GO:0010639	Colorectum	AD	negative regulation of organelle organization	114/3918	348/18723	1.41e-07	6.49e-06	114
GO:0032272	Colorectum	AD	negative regulation of protein polymerization	36/3918	80/18723	1.13e-06	3.72e-05	36
GO:0061572	Colorectum	AD	actin filament bundle organization	60/3918	161/18723	1.33e-06	4.23e-05	60

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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

EPS8

SNV

Missense_Mutation

c.982N>C

p.Phe328Leu

p.F328L

Q12929

protein_coding

tolerated(0.05)

possibly_damaging(0.533)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

EPS8

SNV

Missense_Mutation

c.1785G>T

p.Leu595Phe

p.L595F

Q12929

protein_coding

tolerated(0.32)

benign(0.003)

TCGA-AO-A0JC-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

fluorouracil

EPS8

SNV

Missense_Mutation

c.1508A>G

p.His503Arg

p.H503R

Q12929

protein_coding

tolerated(0.35)

benign(0)

TCGA-AQ-A04H-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

taxotere

EPS8

SNV

Missense_Mutation

c.220N>T

p.Val74Phe

p.V74F

Q12929

protein_coding

deleterious(0)

possibly_damaging(0.57)

TCGA-B6-A0RP-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

EPS8

SNV

Missense_Mutation

rs776013800

c.287C>G

p.Ala96Gly

p.A96G

Q12929

protein_coding

deleterious(0.01)

possibly_damaging(0.574)

TCGA-C8-A26Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

EPS8

SNV

Missense_Mutation

rs369986759

c.794N>A

p.Arg265His

p.R265H

Q12929

protein_coding

deleterious(0)

benign(0.097)

TCGA-D8-A1J8-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

nolvadex

EPS8

SNV

Missense_Mutation

c.1313A>T

p.Glu438Val

p.E438V

Q12929

protein_coding

deleterious(0)

possibly_damaging(0.459)

TCGA-E9-A22G-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

EPS8

insertion

Frame_Shift_Ins

novel

c.2371_2372insTTGCTGTTTTAGGTAGTATGGCCATTTTCAC

p.Ser791PhefsTer29

p.S791Ffs*29

Q12929

protein_coding

TCGA-A2-A0EY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

EPS8

SNV

Missense_Mutation

rs147224631

c.1300N>T

p.Arg434Cys

p.R434C

Q12929

protein_coding

deleterious(0)

benign(0.125)

TCGA-EA-A410-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

EPS8

SNV

Missense_Mutation

c.1499N>C

p.Arg500Thr

p.R500T

Q12929

protein_coding

tolerated(0.08)

benign(0.024)

TCGA-EK-A2RJ-01

Cervix

cervical & endocervical cancer

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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