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: EIF6

Gene summary for EIF6

Gene summary.

Gene information	Species	Human
	Gene symbol	EIF6
	Gene ID	3692
	Gene name	eukaryotic translation initiation factor 6
	Gene Alias	CAB
	Cytomap	20q11.22
	Gene Type	protein-coding
	GO ID	GO:0000054
	UniProtAcc	P56537

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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
3692	EIF6	GSM4909282	Human	Breast	IDC	8.19e-05	2.62e-01	-0.0288
3692	EIF6	GSM4909288	Human	Breast	IDC	4.69e-02	-8.28e-02	0.0988
3692	EIF6	GSM4909296	Human	Breast	IDC	4.20e-07	6.91e-02	0.1524
3692	EIF6	GSM4909297	Human	Breast	IDC	8.83e-15	-3.78e-02	0.1517
3692	EIF6	GSM4909304	Human	Breast	IDC	1.89e-07	3.83e-01	0.1636
3692	EIF6	GSM4909311	Human	Breast	IDC	1.58e-30	-6.25e-02	0.1534
3692	EIF6	GSM4909312	Human	Breast	IDC	4.75e-10	8.30e-02	0.1552
3692	EIF6	GSM4909313	Human	Breast	IDC	5.94e-03	-2.04e-01	0.0391
3692	EIF6	GSM4909319	Human	Breast	IDC	9.63e-37	-1.82e-01	0.1563
3692	EIF6	GSM4909320	Human	Breast	IDC	8.63e-12	3.07e-01	0.1575
3692	EIF6	GSM4909321	Human	Breast	IDC	3.25e-22	3.06e-01	0.1559
3692	EIF6	brca1	Human	Breast	Precancer	3.51e-64	9.08e-01	-0.0338
3692	EIF6	brca2	Human	Breast	Precancer	3.80e-22	4.53e-01	-0.024
3692	EIF6	brca3	Human	Breast	Precancer	9.28e-33	6.26e-01	-0.0263
3692	EIF6	M2	Human	Breast	IDC	1.18e-02	2.87e-01	0.21
3692	EIF6	NCCBC14	Human	Breast	DCIS	2.24e-04	-1.48e-01	0.2021
3692	EIF6	NCCBC2	Human	Breast	DCIS	6.55e-06	2.45e-03	0.1554
3692	EIF6	NCCBC3	Human	Breast	DCIS	6.64e-03	-8.06e-03	0.1198
3692	EIF6	NCCBC5	Human	Breast	DCIS	1.30e-11	-7.75e-03	0.2046
3692	EIF6	P1	Human	Breast	IDC	6.96e-16	-2.50e-01	0.1527

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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:00460349	Breast	Precancer	ATP metabolic process	82/1080	277/18723	1.94e-36	5.19e-33	82
GO:00060918	Breast	Precancer	generation of precursor metabolites and energy	94/1080	490/18723	1.54e-25	1.64e-22	94
GO:00226139	Breast	Precancer	ribonucleoprotein complex biogenesis	79/1080	463/18723	2.11e-18	1.03e-15	79
GO:00718269	Breast	Precancer	ribonucleoprotein complex subunit organization	48/1080	227/18723	2.68e-15	8.45e-13	48
GO:00226189	Breast	Precancer	ribonucleoprotein complex assembly	47/1080	220/18723	3.47e-15	1.03e-12	47
GO:00422549	Breast	Precancer	ribosome biogenesis	52/1080	299/18723	7.35e-13	1.51e-10	52
GO:00064138	Breast	Precancer	translational initiation	30/1080	118/18723	3.23e-12	5.58e-10	30
GO:00064179	Breast	Precancer	regulation of translation	67/1080	468/18723	4.71e-12	7.64e-10	67
GO:00457279	Breast	Precancer	positive regulation of translation	32/1080	136/18723	5.89e-12	9.27e-10	32
GO:00422559	Breast	Precancer	ribosome assembly	21/1080	61/18723	1.06e-11	1.53e-09	21
GO:00422739	Breast	Precancer	ribosomal large subunit biogenesis	22/1080	72/18723	5.03e-11	5.61e-09	22
GO:00342509	Breast	Precancer	positive regulation of cellular amide metabolic process	33/1080	162/18723	1.72e-10	1.77e-08	33
GO:00063646	Breast	Precancer	rRNA processing	35/1080	225/18723	7.90e-08	4.60e-06	35
GO:00160726	Breast	Precancer	rRNA metabolic process	36/1080	236/18723	8.59e-08	4.84e-06	36
GO:00196938	Breast	Precancer	ribose phosphate metabolic process	49/1080	396/18723	3.81e-07	1.78e-05	49
GO:00091509	Breast	Precancer	purine ribonucleotide metabolic process	46/1080	368/18723	6.47e-07	2.71e-05	46
GO:00091179	Breast	Precancer	nucleotide metabolic process	56/1080	489/18723	7.40e-07	3.00e-05	56
GO:00092598	Breast	Precancer	ribonucleotide metabolic process	47/1080	385/18723	9.69e-07	3.84e-05	47
GO:00469398	Breast	Precancer	nucleotide phosphorylation	20/1080	101/18723	1.07e-06	4.18e-05	20
GO:00067539	Breast	Precancer	nucleoside phosphate metabolic process	56/1080	497/18723	1.24e-06	4.70e-05	56

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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

EIF6

SNV

Missense_Mutation

c.427G>T

p.Ala143Ser

p.A143S

P56537

protein_coding

tolerated(0.05)

benign(0.192)

TCGA-CM-6163-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

EIF6

SNV

Missense_Mutation

novel

c.268N>T

p.Asp90Tyr

p.D90Y

P56537

protein_coding

deleterious(0)

probably_damaging(0.969)

TCGA-A5-A0G1-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

EIF6

SNV

Missense_Mutation

novel

c.268N>T

p.Asp90Tyr

p.D90Y

P56537

protein_coding

deleterious(0)

probably_damaging(0.969)

TCGA-A5-A0GG-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

EIF6

SNV

Missense_Mutation

c.205N>A

p.Gly69Ser

p.G69S

P56537

protein_coding

deleterious(0)

probably_damaging(0.957)

TCGA-AJ-A3EL-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

EIF6

SNV

Missense_Mutation

c.368G>T

p.Arg123Met

p.R123M

P56537

protein_coding

deleterious(0.01)

benign(0.142)

TCGA-AP-A059-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

EIF6

SNV

Missense_Mutation

c.200G>T

p.Arg67Met

p.R67M

P56537

protein_coding

deleterious(0)

possibly_damaging(0.838)

TCGA-AP-A059-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

EIF6

SNV

Missense_Mutation

rs144752898

c.430G>A

p.Asp144Asn

p.D144N

P56537

protein_coding

tolerated(0.42)

benign(0.009)

TCGA-AP-A1DV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

EIF6

SNV

Missense_Mutation

rs773641573

c.254N>A

p.Arg85His

p.R85H

P56537

protein_coding

deleterious(0.01)

possibly_damaging(0.9)

TCGA-BG-A0M9-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

EIF6

SNV

Missense_Mutation

novel

c.313N>A

p.Gly105Ser

p.G105S

P56537

protein_coding

deleterious(0.04)

probably_damaging(0.996)

TCGA-EO-A22U-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

EIF6

SNV

Missense_Mutation

rs768741006

c.511G>A

p.Asp171Asn

p.D171N

P56537

protein_coding

tolerated(0.07)

benign(0.151)

TCGA-FI-A2D0-01

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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