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: ELF4

Gene summary for ELF4

Gene summary.

Gene information	Species	Human
	Gene symbol	ELF4
	Gene ID	2000
	Gene name	E74 like ETS transcription factor 4
	Gene Alias	ELFR
	Cytomap	Xq26.1
	Gene Type	protein-coding
	GO ID	GO:0001775
	UniProtAcc	Q99607

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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
2000	ELF4	HTA11_2487_2000001011	Human	Colorectum	SER	1.44e-02	2.75e-01	-0.1808
2000	ELF4	HTA11_1938_2000001011	Human	Colorectum	AD	2.41e-03	2.69e-01	-0.0811
2000	ELF4	HTA11_347_2000001011	Human	Colorectum	AD	2.57e-07	3.66e-01	-0.1954
2000	ELF4	HTA11_411_2000001011	Human	Colorectum	SER	7.47e-04	7.66e-01	-0.2602
2000	ELF4	HTA11_696_2000001011	Human	Colorectum	AD	8.79e-10	3.70e-01	-0.1464
2000	ELF4	HTA11_5212_2000001011	Human	Colorectum	AD	6.14e-03	4.20e-01	-0.2061
2000	ELF4	HTA11_99999974143_84620	Human	Colorectum	MSS	4.34e-03	2.80e-01	0.3005
2000	ELF4	LZE24T	Human	Esophagus	ESCC	1.02e-04	1.46e-01	0.0596
2000	ELF4	P1T-E	Human	Esophagus	ESCC	1.37e-02	1.19e-01	0.0875
2000	ELF4	P5T-E	Human	Esophagus	ESCC	1.13e-06	2.10e-02	0.1327
2000	ELF4	P8T-E	Human	Esophagus	ESCC	4.50e-09	1.05e-01	0.0889
2000	ELF4	P9T-E	Human	Esophagus	ESCC	5.47e-03	1.16e-01	0.1131
2000	ELF4	P10T-E	Human	Esophagus	ESCC	4.34e-08	1.90e-01	0.116
2000	ELF4	P12T-E	Human	Esophagus	ESCC	7.71e-07	6.64e-02	0.1122
2000	ELF4	P15T-E	Human	Esophagus	ESCC	2.79e-06	7.46e-02	0.1149
2000	ELF4	P17T-E	Human	Esophagus	ESCC	1.24e-03	2.19e-01	0.1278
2000	ELF4	P20T-E	Human	Esophagus	ESCC	4.34e-06	1.84e-01	0.1124
2000	ELF4	P21T-E	Human	Esophagus	ESCC	1.20e-08	2.56e-01	0.1617
2000	ELF4	P22T-E	Human	Esophagus	ESCC	2.45e-11	2.18e-01	0.1236
2000	ELF4	P23T-E	Human	Esophagus	ESCC	1.93e-08	3.16e-01	0.108

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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
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma

∗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:004211018	Esophagus	ESCC	T cell activation	256/8552	487/18723	1.18e-03	5.87e-03	256
GO:004211016	Oral cavity	OSCC	T cell activation	245/7305	487/18723	2.00e-07	3.22e-06	245
GO:004209816	Oral cavity	OSCC	T cell proliferation	100/7305	199/18723	7.93e-04	4.27e-03	100
GO:00466333	Oral cavity	OSCC	alpha-beta T cell proliferation	24/7305	38/18723	2.21e-03	1.00e-02	24
GO:00706618	Oral cavity	OSCC	leukocyte proliferation	145/7305	318/18723	9.31e-03	3.33e-02	145
GO:00466517	Oral cavity	OSCC	lymphocyte proliferation	131/7305	288/18723	1.41e-02	4.67e-02	131
GO:0022613113	Thyroid	PTC	ribonucleoprotein complex biogenesis	292/5968	463/18723	3.24e-44	2.05e-40	292
GO:0008380113	Thyroid	PTC	RNA splicing	273/5968	434/18723	4.44e-41	1.40e-37	273
GO:0000375113	Thyroid	PTC	RNA splicing, via transesterification reactions	202/5968	324/18723	6.81e-30	3.91e-27	202
GO:0000377113	Thyroid	PTC	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	199/5968	320/18723	2.96e-29	1.44e-26	199
GO:0000398113	Thyroid	PTC	mRNA splicing, via spliceosome	199/5968	320/18723	2.96e-29	1.44e-26	199
GO:1903311112	Thyroid	PTC	regulation of mRNA metabolic process	181/5968	288/18723	1.60e-27	5.94e-25	181
GO:0050684112	Thyroid	PTC	regulation of mRNA processing	98/5968	137/18723	1.53e-21	3.10e-19	98
GO:0043484113	Thyroid	PTC	regulation of RNA splicing	102/5968	148/18723	2.03e-20	3.21e-18	102
GO:0071826113	Thyroid	PTC	ribonucleoprotein complex subunit organization	134/5968	227/18723	2.34e-17	2.24e-15	134
GO:0006417113	Thyroid	PTC	regulation of translation	236/5968	468/18723	2.70e-17	2.52e-15	236
GO:0022618113	Thyroid	PTC	ribonucleoprotein complex assembly	130/5968	220/18723	6.25e-17	5.47e-15	130
GO:0048024113	Thyroid	PTC	regulation of mRNA splicing, via spliceosome	71/5968	101/18723	2.39e-15	1.71e-13	71
GO:1903313110	Thyroid	PTC	positive regulation of mRNA metabolic process	76/5968	118/18723	3.60e-13	1.80e-11	76
GO:0001701111	Thyroid	PTC	in utero embryonic development	175/5968	367/18723	1.40e-10	4.73e-09	175

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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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
ELF4	IMENT	Colorectum	ADJ	GLI4,AC025159.1,LAMB3, etc.	2.95e-01
ELF4	MSC.SEC	Liver	NAFLD	ITGB2,LAIR1,SPI1, etc.	5.42e-01
ELF4	NEUT	Lung	ADJ	CCDC26,AC024028.1,TMC4, etc.	5.03e-03
ELF4	M2MAC	Oral cavity	LP	SRGAP2C,TYW1B,NOTCH1, etc.	2.33e-01
ELF4	BAS	Skin	cSCC	ANKRD33B,AADACL2-AS1,FNDC3B, etc.	1.23e-01
ELF4	PMC	Stomach	ADJ	VIM,FAM134A,THRB, etc.	3.53e-01
ELF4	PMC	Stomach	CSG	VIM,FAM134A,THRB, etc.	4.96e-01
ELF4	PMC	Stomach	GC	VIM,FAM134A,THRB, etc.	3.77e-01
ELF4	PMC	Stomach	SIM	VIM,FAM134A,THRB, etc.	4.40e-01

∗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

ELF4

SNV

Missense_Mutation

c.1447N>G

p.Leu483Val

p.L483V

Q99607

protein_coding

tolerated(0.3)

possibly_damaging(0.679)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ELF4

SNV

Missense_Mutation

novel

c.1705C>T

p.Leu569Phe

p.L569F

Q99607

protein_coding

deleterious(0.02)

possibly_damaging(0.879)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ELF4

SNV

Missense_Mutation

rs776215676

c.922G>A

p.Glu308Lys

p.E308K

Q99607

protein_coding

tolerated(0.07)

possibly_damaging(0.642)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ELF4

SNV

Missense_Mutation

c.1517G>A

p.Gly506Glu

p.G506E

Q99607

protein_coding

tolerated(0.48)

benign(0.18)

TCGA-AR-A24X-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

ELF4

SNV

Missense_Mutation

c.1015N>T

p.Ala339Ser

p.A339S

Q99607

protein_coding

tolerated(0.68)

benign(0.005)

TCGA-C8-A1HI-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

ELF4

SNV

Missense_Mutation

c.1447C>T

p.Leu483Phe

p.L483F

Q99607

protein_coding

tolerated(0.34)

possibly_damaging(0.88)

TCGA-GM-A2DL-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

ELF4

insertion

Frame_Shift_Ins

novel

c.52_53insA

p.Gly18GlufsTer4

p.G18Efs*4

Q99607

protein_coding

TCGA-A8-A09D-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

ELF4

insertion

In_Frame_Ins

novel

c.1694_1695insGCGGAGTCGCAGTCA

p.Thr565_Leu566insArgSerArgSerHis

p.T565_L566insRSRSH

Q99607

protein_coding

TCGA-AN-A03X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ELF4

insertion

Frame_Shift_Ins

novel

c.1692_1693insCCTCGCGGACCAGCAGGTGAGC

p.Thr565ProfsTer57

p.T565Pfs*57

Q99607

protein_coding

TCGA-AN-A03X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ELF4

insertion

Frame_Shift_Ins

novel

c.317_318insGACTGGGAAATCAAAGAAGAGAAGTAAGTGGGGGAGAGTG

p.Asp106GlufsTer18

p.D106Efs*18

Q99607

protein_coding

TCGA-B6-A0I9-01

Breast

breast invasive carcinoma

Female

<65

III/IV

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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