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: EIF2S2

Gene summary for EIF2S2

Gene summary.

Gene information	Species	Human
	Gene symbol	EIF2S2
	Gene ID	8894
	Gene name	eukaryotic translation initiation factor 2 subunit beta
	Gene Alias	EIF2
	Cytomap	20q11.22
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	P20042

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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
8894	EIF2S2	GSM5353222_PA_PB2B_Pool_1_3_S52_L002	Human	Prostate	Tumor	8.88e-20	-8.51e-01	0.1608
8894	EIF2S2	GSM5353223_PA_PB2B_Pool_2_S26_L001	Human	Prostate	Tumor	1.82e-09	-7.91e-01	0.1604
8894	EIF2S2	GSM5353224_PA_PR5186_Pool_1_2_3_S27_L001	Human	Prostate	Tumor	4.68e-08	-7.22e-01	0.1621
8894	EIF2S2	GSM5353225_PA_PR5196-1_Pool_1_2_3_S53_L002	Human	Prostate	Tumor	1.67e-05	-8.27e-01	0.1619
8894	EIF2S2	GSM5353227_PA_PR5199-193K_Pool_1_2_3_S55_L002	Human	Prostate	Tumor	1.23e-13	-8.17e-01	0.1602
8894	EIF2S2	GSM5353232_PA_PR5249_T1_S3_L001	Human	Prostate	Tumor	3.92e-03	-8.98e-01	0.1439
8894	EIF2S2	GSM5353236_PA_PR5251_T1_S7_L001	Human	Prostate	Tumor	2.15e-06	-8.39e-01	0.1608
8894	EIF2S2	GSM5353240_PA_PR5254_T1_S15_L001	Human	Prostate	Tumor	6.69e-22	-8.12e-01	0.1575
8894	EIF2S2	GSM5353243_PA_PR5261_T1_S23_L002	Human	Prostate	Tumor	9.58e-34	-9.41e-01	0.1545
8894	EIF2S2	GSM5353244_PA_PR5261_T2_S24_L002	Human	Prostate	Tumor	6.51e-24	-9.15e-01	0.1569
8894	EIF2S2	GSM5353247_PA_PR5269_3_S27_L002	Human	Prostate	Tumor	8.07e-03	-9.71e-01	0.1532
8894	EIF2S2	P4_S8_cSCC	Human	Skin	cSCC	3.15e-13	3.56e-01	-0.3095
8894	EIF2S2	P5_S10_cSCC	Human	Skin	cSCC	1.20e-21	5.08e-01	-0.299
8894	EIF2S2	P1_cSCC	Human	Skin	cSCC	1.69e-56	2.05e+00	0.0292
8894	EIF2S2	P2_cSCC	Human	Skin	cSCC	1.90e-67	1.68e+00	-0.024
8894	EIF2S2	P4_cSCC	Human	Skin	cSCC	8.12e-65	1.78e+00	-0.00290000000000005
8894	EIF2S2	P10_cSCC	Human	Skin	cSCC	2.57e-67	2.07e+00	0.1017
8894	EIF2S2	cSCC_p10	Human	Skin	cSCC	9.79e-11	4.79e-01	-0.2095
8894	EIF2S2	cSCC_p8	Human	Skin	cSCC	3.16e-13	3.34e-01	-0.1971
8894	EIF2S2	cSCC_p9	Human	Skin	cSCC	8.95e-11	2.18e-01	-0.1991

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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
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:0002181	Colorectum	AD	cytoplasmic translation	109/3918	148/18723	3.40e-43	2.13e-39	109
GO:0022618	Colorectum	AD	ribonucleoprotein complex assembly	92/3918	220/18723	1.49e-12	2.60e-10	92
GO:0071826	Colorectum	AD	ribonucleoprotein complex subunit organization	94/3918	227/18723	1.70e-12	2.87e-10	94
GO:0022613	Colorectum	AD	ribonucleoprotein complex biogenesis	151/3918	463/18723	1.96e-09	1.39e-07	151
GO:0002183	Colorectum	AD	cytoplasmic translational initiation	21/3918	34/18723	2.73e-07	1.09e-05	21
GO:0001732	Colorectum	AD	formation of cytoplasmic translation initiation complex	13/3918	16/18723	4.27e-07	1.64e-05	13
GO:0006413	Colorectum	AD	translational initiation	45/3918	118/18723	1.35e-05	2.92e-04	45
GO:0001701	Colorectum	AD	in utero embryonic development	110/3918	367/18723	2.36e-05	4.62e-04	110
GO:0061458	Colorectum	AD	reproductive system development	116/3918	427/18723	1.11e-03	1.01e-02	116
GO:0048608	Colorectum	AD	reproductive structure development	114/3918	424/18723	1.78e-03	1.47e-02	114
GO:0001731	Colorectum	AD	formation of translation preinitiation complex	7/3918	11/18723	2.59e-03	1.96e-02	7
GO:00021812	Colorectum	MSS	cytoplasmic translation	108/3467	148/18723	1.78e-47	1.11e-43	108
GO:00718262	Colorectum	MSS	ribonucleoprotein complex subunit organization	90/3467	227/18723	6.88e-14	1.78e-11	90
GO:00226182	Colorectum	MSS	ribonucleoprotein complex assembly	88/3467	220/18723	7.12e-14	1.78e-11	88
GO:00226132	Colorectum	MSS	ribonucleoprotein complex biogenesis	144/3467	463/18723	2.76e-11	3.67e-09	144
GO:00021832	Colorectum	MSS	cytoplasmic translational initiation	21/3467	34/18723	2.99e-08	1.67e-06	21
GO:00017322	Colorectum	MSS	formation of cytoplasmic translation initiation complex	13/3467	16/18723	9.42e-08	4.63e-06	13
GO:00064132	Colorectum	MSS	translational initiation	43/3467	118/18723	3.19e-06	9.38e-05	43
GO:00614582	Colorectum	MSS	reproductive system development	115/3467	427/18723	9.86e-06	2.39e-04	115
GO:00486082	Colorectum	MSS	reproductive structure development	113/3467	424/18723	1.94e-05	4.18e-04	113

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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

EIF2S2

SNV

Missense_Mutation

c.949N>T

p.Gly317Cys

p.G317C

P20042

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A7-A4SE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

EIF2S2

SNV

Missense_Mutation

c.471N>G

p.Ile157Met

p.I157M

P20042

protein_coding

deleterious(0.03)

possibly_damaging(0.809)

TCGA-BH-A0HP-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

doxorubicin

EIF2S2

SNV

Missense_Mutation

c.974N>A

p.Arg325Gln

p.R325Q

P20042

protein_coding

deleterious(0.02)

probably_damaging(0.921)

TCGA-E2-A14N-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

EIF2S2

SNV

Missense_Mutation

c.782G>A

p.Arg261Lys

p.R261K

P20042

protein_coding

deleterious(0.03)

probably_damaging(0.946)

TCGA-EW-A1J2-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

EIF2S2

insertion

Frame_Shift_Ins

novel

c.869_870insTCCCAATGTTGGATATTTCTACATGAATAAAGCAAGGATCAGTG

p.Leu291ProfsTer87

p.L291Pfs*87

P20042

protein_coding

TCGA-A7-A0CJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

EIF2S2

insertion

In_Frame_Ins

novel

c.887_888insCCAAGTCCTCCCCCAGCT

p.Arg296_Leu297insGlnValLeuProGlnLeu

p.R296_L297insQVLPQL

P20042

protein_coding

TCGA-A8-A090-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

EIF2S2

SNV

Missense_Mutation

c.727N>A

p.Glu243Lys

p.E243K

P20042

protein_coding

deleterious(0)

probably_damaging(0.973)

TCGA-MU-A8JM-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

EIF2S2

SNV

Missense_Mutation

c.237N>T

p.Lys79Asn

p.K79N

P20042

protein_coding

tolerated(0.11)

probably_damaging(0.95)

TCGA-AA-3977-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

EIF2S2

SNV

Missense_Mutation

c.570N>T

p.Lys190Asn

p.K190N

P20042

protein_coding

tolerated(0.22)

probably_damaging(0.991)

TCGA-CA-6717-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Chemotherapy

oxaliplatin

EIF2S2

SNV

Missense_Mutation

novel

c.220N>C

p.Asn74His

p.N74H

P20042

protein_coding

deleterious(0.01)

benign(0.226)

TCGA-AJ-A3EL-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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