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: EIF4E2

Gene summary for EIF4E2

Gene summary.

Gene information	Species	Human
	Gene symbol	EIF4E2
	Gene ID	9470
	Gene name	eukaryotic translation initiation factor 4E family member 2
	Gene Alias	4E-LP
	Cytomap	2q37.1
	Gene Type	protein-coding
	GO ID	GO:0006412
	UniProtAcc	O60573

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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
9470	EIF4E2	LZE2T	Human	Esophagus	ESCC	2.74e-02	4.27e-01	0.082
9470	EIF4E2	LZE4T	Human	Esophagus	ESCC	5.53e-20	5.07e-01	0.0811
9470	EIF4E2	LZE7T	Human	Esophagus	ESCC	1.90e-14	8.50e-01	0.0667
9470	EIF4E2	LZE8T	Human	Esophagus	ESCC	8.35e-12	5.26e-01	0.067
9470	EIF4E2	LZE20T	Human	Esophagus	ESCC	3.96e-12	4.85e-01	0.0662
9470	EIF4E2	LZE22D1	Human	Esophagus	HGIN	1.42e-03	7.51e-02	0.0595
9470	EIF4E2	LZE22T	Human	Esophagus	ESCC	1.20e-02	3.34e-01	0.068
9470	EIF4E2	LZE24T	Human	Esophagus	ESCC	1.77e-20	6.30e-01	0.0596
9470	EIF4E2	LZE21T	Human	Esophagus	ESCC	7.87e-04	2.69e-01	0.0655
9470	EIF4E2	LZE6T	Human	Esophagus	ESCC	3.41e-17	6.55e-01	0.0845
9470	EIF4E2	P1T-E	Human	Esophagus	ESCC	7.04e-11	4.75e-01	0.0875
9470	EIF4E2	P2T-E	Human	Esophagus	ESCC	5.19e-48	8.14e-01	0.1177
9470	EIF4E2	P4T-E	Human	Esophagus	ESCC	1.19e-33	6.56e-01	0.1323
9470	EIF4E2	P5T-E	Human	Esophagus	ESCC	1.27e-41	8.37e-01	0.1327
9470	EIF4E2	P8T-E	Human	Esophagus	ESCC	1.28e-34	6.70e-01	0.0889
9470	EIF4E2	P9T-E	Human	Esophagus	ESCC	7.26e-34	8.42e-01	0.1131
9470	EIF4E2	P10T-E	Human	Esophagus	ESCC	2.40e-46	8.30e-01	0.116
9470	EIF4E2	P11T-E	Human	Esophagus	ESCC	3.48e-18	8.02e-01	0.1426
9470	EIF4E2	P12T-E	Human	Esophagus	ESCC	6.50e-49	8.66e-01	0.1122
9470	EIF4E2	P15T-E	Human	Esophagus	ESCC	2.75e-54	1.12e+00	0.1149

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:000641727	Esophagus	HGIN	regulation of translation	139/2587	468/18723	1.46e-19	7.98e-17	139
GO:000641320	Esophagus	HGIN	translational initiation	55/2587	118/18723	7.33e-18	2.31e-15	55
GO:00342496	Esophagus	HGIN	negative regulation of cellular amide metabolic process	66/2587	273/18723	2.74e-06	9.60e-05	66
GO:00171486	Esophagus	HGIN	negative regulation of translation	59/2587	245/18723	1.03e-05	2.96e-04	59
GO:0006413110	Esophagus	ESCC	translational initiation	100/8552	118/18723	1.16e-18	1.25e-16	100
GO:0006417111	Esophagus	ESCC	regulation of translation	304/8552	468/18723	1.53e-17	1.33e-15	304
GO:00601487	Esophagus	ESCC	positive regulation of posttranscriptional gene silencing	24/8552	31/18723	3.19e-04	1.89e-03	24
GO:00609667	Esophagus	ESCC	regulation of gene silencing by RNA	37/8552	53/18723	3.25e-04	1.92e-03	37
GO:00601479	Esophagus	ESCC	regulation of posttranscriptional gene silencing	36/8552	52/18723	5.05e-04	2.79e-03	36
GO:20006377	Esophagus	ESCC	positive regulation of gene silencing by miRNA	23/8552	30/18723	5.47e-04	3.00e-03	23
GO:006096410	Esophagus	ESCC	regulation of gene silencing by miRNA	34/8552	49/18723	6.74e-04	3.56e-03	34
GO:00609686	Esophagus	ESCC	regulation of gene silencing	48/8552	81/18723	9.54e-03	3.30e-02	48
GO:003424914	Esophagus	ESCC	negative regulation of cellular amide metabolic process	144/8552	273/18723	1.08e-02	3.67e-02	144
GO:000641312	Liver	Cirrhotic	translational initiation	76/4634	118/18723	8.36e-20	2.18e-17	76
GO:000641712	Liver	Cirrhotic	regulation of translation	194/4634	468/18723	7.28e-16	8.79e-14	194
GO:003424911	Liver	Cirrhotic	negative regulation of cellular amide metabolic process	100/4634	273/18723	7.34e-06	1.13e-04	100
GO:200063711	Liver	Cirrhotic	positive regulation of gene silencing by miRNA	18/4634	30/18723	4.27e-05	5.03e-04	18
GO:00609645	Liver	Cirrhotic	regulation of gene silencing by miRNA	25/4634	49/18723	6.57e-05	7.47e-04	25
GO:006014711	Liver	Cirrhotic	regulation of posttranscriptional gene silencing	26/4634	52/18723	7.35e-05	8.23e-04	26
GO:006014811	Liver	Cirrhotic	positive regulation of posttranscriptional gene silencing	18/4634	31/18723	7.83e-05	8.61e-04	18

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0406629	Esophagus	ESCC	HIF-1 signaling pathway	75/4205	109/8465	3.66e-05	1.68e-04	8.60e-05	75
hsa049109	Esophagus	ESCC	Insulin signaling pathway	89/4205	137/8465	1.97e-04	7.32e-04	3.75e-04	89
hsa0152110	Esophagus	ESCC	EGFR tyrosine kinase inhibitor resistance	55/4205	79/8465	2.44e-04	8.78e-04	4.50e-04	55
hsa041505	Esophagus	ESCC	mTOR signaling pathway	98/4205	156/8465	5.81e-04	1.95e-03	9.97e-04	98
hsa0421114	Esophagus	ESCC	Longevity regulating pathway	58/4205	89/8465	2.19e-03	6.16e-03	3.16e-03	58
hsa041517	Esophagus	ESCC	PI3K-Akt signaling pathway	197/4205	354/8465	1.24e-02	2.83e-02	1.45e-02	197
hsa04066113	Esophagus	ESCC	HIF-1 signaling pathway	75/4205	109/8465	3.66e-05	1.68e-04	8.60e-05	75
hsa0491014	Esophagus	ESCC	Insulin signaling pathway	89/4205	137/8465	1.97e-04	7.32e-04	3.75e-04	89
hsa0152115	Esophagus	ESCC	EGFR tyrosine kinase inhibitor resistance	55/4205	79/8465	2.44e-04	8.78e-04	4.50e-04	55
hsa0415013	Esophagus	ESCC	mTOR signaling pathway	98/4205	156/8465	5.81e-04	1.95e-03	9.97e-04	98
hsa0421115	Esophagus	ESCC	Longevity regulating pathway	58/4205	89/8465	2.19e-03	6.16e-03	3.16e-03	58
hsa0415114	Esophagus	ESCC	PI3K-Akt signaling pathway	197/4205	354/8465	1.24e-02	2.83e-02	1.45e-02	197
hsa0491021	Liver	Cirrhotic	Insulin signaling pathway	56/2530	137/8465	3.74e-03	1.50e-02	9.26e-03	56
hsa0406612	Liver	Cirrhotic	HIF-1 signaling pathway	46/2530	109/8465	4.00e-03	1.59e-02	9.78e-03	46
hsa015216	Liver	Cirrhotic	EGFR tyrosine kinase inhibitor resistance	35/2530	79/8465	4.50e-03	1.70e-02	1.05e-02	35
hsa042118	Liver	Cirrhotic	Longevity regulating pathway	37/2530	89/8465	1.22e-02	3.89e-02	2.40e-02	37
hsa0491031	Liver	Cirrhotic	Insulin signaling pathway	56/2530	137/8465	3.74e-03	1.50e-02	9.26e-03	56
hsa0406613	Liver	Cirrhotic	HIF-1 signaling pathway	46/2530	109/8465	4.00e-03	1.59e-02	9.78e-03	46
hsa0152111	Liver	Cirrhotic	EGFR tyrosine kinase inhibitor resistance	35/2530	79/8465	4.50e-03	1.70e-02	1.05e-02	35
hsa0421111	Liver	Cirrhotic	Longevity regulating pathway	37/2530	89/8465	1.22e-02	3.89e-02	2.40e-02	37

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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

EIF4E2

SNV

Missense_Mutation

c.443G>T

p.Trp148Leu

p.W148L

O60573

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-BH-A0HA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

EIF4E2

SNV

Missense_Mutation

rs375938541

c.506N>T

p.Ala169Val

p.A169V

O60573

protein_coding

tolerated(0.18)

benign(0.052)

TCGA-D8-A1Y1-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

tamoxiphen

EIF4E2

SNV

Missense_Mutation

c.605G>A

p.Arg202Gln

p.R202Q

O60573

protein_coding

tolerated(0.05)

benign(0.026)

TCGA-D8-A27G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

EIF4E2

SNV

Missense_Mutation

novel

c.64G>A

p.Gly22Ser

p.G22S

protein_coding

unknown(0)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

EIF4E2

SNV

Missense_Mutation

novel

c.343N>A

p.Leu115Ile

p.L115I

O60573

protein_coding

tolerated(0.09)

benign(0.212)

TCGA-AG-A002-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

EIF4E2

SNV

Missense_Mutation

novel

c.291T>G

p.Phe97Leu

p.F97L

O60573

protein_coding

tolerated(0.55)

benign(0.003)

TCGA-EI-6917-01

Colorectum

rectum adenocarcinoma

Male

<65

III/IV

Chemotherapy

5fluorouracil+oxaciplatina+l-folinian

EIF4E2

insertion

Frame_Shift_Ins

novel

c.182_183insAATTAAAAAAGGA

p.Phe62IlefsTer22

p.F62Ifs*22

O60573

protein_coding

TCGA-AM-5820-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

EIF4E2

SNV

Missense_Mutation

rs142409429

c.307N>T

p.Arg103Cys

p.R103C

O60573

protein_coding

tolerated(0.06)

benign(0.11)

TCGA-AP-A0LE-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

EIF4E2

SNV

Missense_Mutation

novel

c.398N>A

p.Gly133Asp

p.G133D

O60573

protein_coding

deleterious(0.04)

probably_damaging(0.953)

TCGA-AX-A3G8-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

EIF4E2

SNV

Missense_Mutation

novel

c.392N>C

p.Asn131Thr

p.N131T

O60573

protein_coding

tolerated(0.12)

benign(0.042)

TCGA-B5-A3FA-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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