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: EIF4A2

Gene summary for EIF4A2

Gene summary.

Gene information	Species	Human
	Gene symbol	EIF4A2
	Gene ID	1974
	Gene name	eukaryotic translation initiation factor 4A2
	Gene Alias	BM-010
	Cytomap	3q27.3
	Gene Type	protein-coding
	GO ID	GO:0002181
	UniProtAcc	Q14240

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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
1974	EIF4A2	GSM4909277	Human	Breast	Precancer	3.86e-02	3.20e-01	0.0177
1974	EIF4A2	GSM4909285	Human	Breast	IDC	2.54e-16	3.96e-01	0.21
1974	EIF4A2	GSM4909286	Human	Breast	IDC	2.80e-08	-4.46e-02	0.1081
1974	EIF4A2	GSM4909287	Human	Breast	IDC	6.59e-07	-3.59e-01	0.2057
1974	EIF4A2	GSM4909288	Human	Breast	IDC	7.57e-07	-5.61e-01	0.0988
1974	EIF4A2	GSM4909290	Human	Breast	IDC	3.11e-13	-4.83e-01	0.2096
1974	EIF4A2	GSM4909291	Human	Breast	IDC	1.49e-12	-5.69e-01	0.1753
1974	EIF4A2	GSM4909294	Human	Breast	IDC	3.09e-10	-4.54e-01	0.2022
1974	EIF4A2	GSM4909296	Human	Breast	IDC	1.43e-52	-9.30e-01	0.1524
1974	EIF4A2	GSM4909297	Human	Breast	IDC	3.74e-30	7.95e-02	0.1517
1974	EIF4A2	GSM4909298	Human	Breast	IDC	4.57e-12	-2.75e-01	0.1551
1974	EIF4A2	GSM4909301	Human	Breast	IDC	4.86e-23	-6.29e-01	0.1577
1974	EIF4A2	GSM4909302	Human	Breast	IDC	3.18e-08	-3.73e-01	0.1545
1974	EIF4A2	GSM4909304	Human	Breast	IDC	1.00e-06	-2.79e-01	0.1636
1974	EIF4A2	GSM4909306	Human	Breast	IDC	6.35e-06	-2.45e-01	0.1564
1974	EIF4A2	GSM4909307	Human	Breast	IDC	6.37e-09	-3.99e-01	0.1569
1974	EIF4A2	GSM4909309	Human	Breast	IDC	2.15e-10	-4.15e-01	0.0483
1974	EIF4A2	GSM4909311	Human	Breast	IDC	7.60e-59	-8.43e-01	0.1534
1974	EIF4A2	GSM4909312	Human	Breast	IDC	1.19e-07	-1.63e-01	0.1552
1974	EIF4A2	GSM4909313	Human	Breast	IDC	7.43e-05	-1.29e-01	0.0391

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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
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
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:00064461	Colorectum	MSS	regulation of translational initiation	26/3467	79/18723	1.56e-03	1.42e-02	26
GO:00021813	Colorectum	MSI-H	cytoplasmic translation	100/1319	148/18723	1.50e-79	8.31e-76	100
GO:00064133	Colorectum	MSI-H	translational initiation	37/1319	118/18723	3.18e-15	8.83e-13	37
GO:00021833	Colorectum	MSI-H	cytoplasmic translational initiation	19/1319	34/18723	7.60e-14	1.84e-11	19
GO:00064173	Colorectum	MSI-H	regulation of translation	73/1319	468/18723	9.89e-11	1.66e-08	73
GO:00064462	Colorectum	MSI-H	regulation of translational initiation	21/1319	79/18723	7.80e-08	8.02e-06	21
GO:00513483	Colorectum	MSI-H	negative regulation of transferase activity	38/1319	268/18723	2.89e-05	1.17e-03	38
GO:00021814	Colorectum	FAP	cytoplasmic translation	76/2622	148/18723	3.31e-27	2.03e-23	76
GO:00064174	Colorectum	FAP	regulation of translation	111/2622	468/18723	8.47e-09	1.13e-06	111
GO:00021834	Colorectum	FAP	cytoplasmic translational initiation	16/2622	34/18723	3.74e-06	1.29e-04	16
GO:00064463	Colorectum	FAP	regulation of translational initiation	26/2622	79/18723	1.54e-05	4.01e-04	26
GO:00513484	Colorectum	FAP	negative regulation of transferase activity	63/2622	268/18723	1.82e-05	4.57e-04	63
GO:00064134	Colorectum	FAP	translational initiation	34/2622	118/18723	2.13e-05	5.12e-04	34
GO:1990823	Colorectum	FAP	response to leukemia inhibitory factor	23/2622	95/18723	5.32e-03	3.49e-02	23
GO:000218116	Endometrium	AEH	cytoplasmic translation	104/2100	148/18723	1.01e-64	6.07e-61	104
GO:000641310	Endometrium	AEH	translational initiation	42/2100	118/18723	2.68e-12	4.67e-10	42
GO:000218310	Endometrium	AEH	cytoplasmic translational initiation	18/2100	34/18723	2.75e-09	2.06e-07	18
GO:000641716	Endometrium	AEH	regulation of translation	94/2100	468/18723	1.14e-08	7.62e-07	94
GO:00064467	Endometrium	AEH	regulation of translational initiation	25/2100	79/18723	8.99e-07	3.19e-05	25
GO:005134816	Endometrium	AEH	negative regulation of transferase activity	51/2100	268/18723	1.06e-04	1.52e-03	51

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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

EIF4A2

SNV

Missense_Mutation

c.73G>C

p.Glu25Gln

p.E25Q

Q14240

protein_coding

tolerated_low_confidence(0.1)

benign(0.027)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

EIF4A2

SNV

Missense_Mutation

c.1055N>G

p.Thr352Ser

p.T352S

Q14240

protein_coding

tolerated(0.37)

benign(0.001)

TCGA-A8-A079-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

EIF4A2

SNV

Missense_Mutation

c.595G>C

p.Glu199Gln

p.E199Q

Q14240

protein_coding

deleterious(0.05)

benign(0.141)

TCGA-A8-A09G-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

EIF4A2

SNV

Missense_Mutation

c.1107N>T

p.Arg369Ser

p.R369S

Q14240

protein_coding

deleterious(0.01)

benign(0.246)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

EIF4A2

SNV

Missense_Mutation

c.97N>A

p.Asp33Asn

p.D33N

Q14240

protein_coding

tolerated(0.06)

benign(0.005)

TCGA-AR-A0TV-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

EIF4A2

SNV

Missense_Mutation

novel

c.55G>A

p.Asp19Asn

p.D19N

Q14240

protein_coding

tolerated_low_confidence(0.14)

benign(0)

TCGA-AR-A2LH-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

EIF4A2

SNV

Missense_Mutation

c.595N>A

p.Glu199Lys

p.E199K

Q14240

protein_coding

deleterious(0.03)

benign(0.035)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

EIF4A2

SNV

Missense_Mutation

rs199556041

c.1184C>T

p.Thr395Ile

p.T395I

Q14240

protein_coding

deleterious(0.05)

benign(0.005)

TCGA-C8-A26X-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

EIF4A2

SNV

Missense_Mutation

c.1165G>A

p.Glu389Lys

p.E389K

Q14240

protein_coding

deleterious(0)

possibly_damaging(0.648)

TCGA-C8-A26Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

EIF4A2

SNV

Missense_Mutation

novel

c.769N>C

p.Glu257Gln

p.E257Q

Q14240

protein_coding

deleterious(0)

benign(0.372)

TCGA-GI-A2C9-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

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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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