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: EIF3L

Gene summary for EIF3L

Gene summary.

Gene information	Species	Human
	Gene symbol	EIF3L
	Gene ID	51386
	Gene name	eukaryotic translation initiation factor 3 subunit L
	Gene Alias	EIF3EIP
	Cytomap	22q13.1
	Gene Type	protein-coding
	GO ID	GO:0001732
	UniProtAcc	Q9Y262

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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
51386	EIF3L	GSM4909286	Human	Breast	IDC	4.31e-31	6.07e-01	0.1081
51386	EIF3L	GSM4909287	Human	Breast	IDC	2.05e-07	-4.21e-01	0.2057
51386	EIF3L	GSM4909291	Human	Breast	IDC	2.21e-06	-4.81e-01	0.1753
51386	EIF3L	GSM4909293	Human	Breast	IDC	6.42e-18	-3.62e-01	0.1581
51386	EIF3L	GSM4909294	Human	Breast	IDC	8.35e-16	-4.26e-01	0.2022
51386	EIF3L	GSM4909296	Human	Breast	IDC	3.56e-20	-5.07e-01	0.1524
51386	EIF3L	GSM4909297	Human	Breast	IDC	3.38e-23	-2.47e-01	0.1517
51386	EIF3L	GSM4909301	Human	Breast	IDC	1.29e-35	-6.91e-01	0.1577
51386	EIF3L	GSM4909302	Human	Breast	IDC	1.62e-12	-5.08e-01	0.1545
51386	EIF3L	GSM4909304	Human	Breast	IDC	3.30e-07	-2.70e-01	0.1636
51386	EIF3L	GSM4909305	Human	Breast	IDC	2.67e-02	2.94e-01	0.0436
51386	EIF3L	GSM4909307	Human	Breast	IDC	3.69e-17	-5.10e-01	0.1569
51386	EIF3L	GSM4909308	Human	Breast	IDC	2.92e-05	-2.78e-01	0.158
51386	EIF3L	GSM4909309	Human	Breast	IDC	1.21e-12	-5.28e-01	0.0483
51386	EIF3L	GSM4909311	Human	Breast	IDC	6.17e-48	-5.25e-01	0.1534
51386	EIF3L	GSM4909312	Human	Breast	IDC	3.60e-18	1.49e-01	0.1552
51386	EIF3L	GSM4909313	Human	Breast	IDC	4.53e-03	-1.97e-02	0.0391
51386	EIF3L	GSM4909315	Human	Breast	IDC	3.13e-08	-3.70e-01	0.21
51386	EIF3L	GSM4909316	Human	Breast	IDC	5.82e-03	-4.42e-01	0.21
51386	EIF3L	GSM4909317	Human	Breast	IDC	1.20e-03	-3.33e-01	0.1355

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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
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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:000218314	Cervix	HSIL_HPV	cytoplasmic translational initiation	8/737	34/18723	4.06e-05	1.08e-03	8
GO:000173214	Cervix	HSIL_HPV	formation of cytoplasmic translation initiation complex	5/737	16/18723	2.83e-04	4.69e-03	5
GO:000218125	Cervix	N_HPV	cytoplasmic translation	42/534	148/18723	2.61e-30	1.19e-26	42
GO:001603225	Cervix	N_HPV	viral process	33/534	415/18723	1.23e-07	1.15e-05	33
GO:002261325	Cervix	N_HPV	ribonucleoprotein complex biogenesis	30/534	463/18723	2.78e-05	7.49e-04	30
GO:001908012	Cervix	N_HPV	viral gene expression	9/534	94/18723	1.45e-03	1.54e-02	9
GO:002261825	Cervix	N_HPV	ribonucleoprotein complex assembly	15/534	220/18723	1.68e-03	1.72e-02	15
GO:007182625	Cervix	N_HPV	ribonucleoprotein complex subunit organization	15/534	227/18723	2.28e-03	2.12e-02	15
GO:000641324	Cervix	N_HPV	translational initiation	9/534	118/18723	6.69e-03	4.48e-02	9
GO:000218116	Endometrium	AEH	cytoplasmic translation	104/2100	148/18723	1.01e-64	6.07e-61	104
GO:001603216	Endometrium	AEH	viral process	110/2100	415/18723	1.99e-18	1.09e-15	110
GO:002261316	Endometrium	AEH	ribonucleoprotein complex biogenesis	107/2100	463/18723	1.43e-13	4.08e-11	107
GO:007182616	Endometrium	AEH	ribonucleoprotein complex subunit organization	65/2100	227/18723	4.47e-13	1.07e-10	65
GO:002261816	Endometrium	AEH	ribonucleoprotein complex assembly	63/2100	220/18723	1.02e-12	2.24e-10	63
GO:000641310	Endometrium	AEH	translational initiation	42/2100	118/18723	2.68e-12	4.67e-10	42
GO:000173210	Endometrium	AEH	formation of cytoplasmic translation initiation complex	13/2100	16/18723	1.74e-10	1.93e-08	13
GO:000218310	Endometrium	AEH	cytoplasmic translational initiation	18/2100	34/18723	2.75e-09	2.06e-07	18
GO:00190818	Endometrium	AEH	viral translation	8/2100	16/18723	1.38e-04	1.86e-03	8
GO:00190808	Endometrium	AEH	viral gene expression	21/2100	94/18723	1.46e-03	1.22e-02	21
GO:000218117	Endometrium	EEC	cytoplasmic translation	104/2168	148/18723	2.53e-63	1.52e-59	104

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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

EIF3L

SNV

Missense_Mutation

c.136N>G

p.Gln46Glu

p.Q46E

Q9Y262

protein_coding

tolerated(0.87)

benign(0.009)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

EIF3L

SNV

Missense_Mutation

novel

c.502N>T

p.Leu168Phe

p.L168F

Q9Y262

protein_coding

deleterious(0.02)

probably_damaging(0.995)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

EIF3L

SNV

Missense_Mutation

rs201577615

c.1591N>A

p.Ala531Thr

p.A531T

Q9Y262

protein_coding

tolerated(0.06)

possibly_damaging(0.782)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

EIF3L

SNV

Missense_Mutation

rs767371369

c.646N>T

p.Arg216Cys

p.R216C

Q9Y262

protein_coding

tolerated(0.14)

benign(0.067)

TCGA-C8-A12Q-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

EIF3L

insertion

Frame_Shift_Ins

novel

c.689_690insA

p.Leu231ProfsTer22

p.L231Pfs*22

Q9Y262

protein_coding

TCGA-A7-A0CJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

EIF3L

insertion

In_Frame_Ins

novel

c.691_692insGCACCCGGCCTGTTTTTGTATTTTTAGTAGAGATGGGGT

p.Leu231delinsArgThrArgProValPheValPheLeuValGluMetGlyPhe

p.L231delinsRTRPVFVFLVEMGF

Q9Y262

protein_coding

TCGA-A7-A0CJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

EIF3L

deletion

In_Frame_Del

c.1203_1205delNNN

p.Gln402del

p.Q402del

Q9Y262

protein_coding

TCGA-D8-A27N-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

taxol+adriamycin+cyclophosphamide+herceptin

EIF3L

SNV

Missense_Mutation

novel

c.1400N>G

p.Tyr467Cys

p.Y467C

Q9Y262

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

EIF3L

SNV

Missense_Mutation

c.565G>A

p.Glu189Lys

p.E189K

Q9Y262

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-IR-A3LH-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

EIF3L

SNV

Missense_Mutation

rs760820592

c.892N>A

p.Glu298Lys

p.E298K

Q9Y262

protein_coding

deleterious(0.03)

possibly_damaging(0.636)

TCGA-AA-3977-01

Colorectum

colon adenocarcinoma

Male

>=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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