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:000675318	Oral cavity	OSCC	nucleoside phosphate metabolic process	247/7305	497/18723	6.28e-07	8.96e-06	247
GO:000911719	Oral cavity	OSCC	nucleotide metabolic process	243/7305	489/18723	7.80e-07	1.09e-05	243
GO:00004602	Oral cavity	OSCC	maturation of 5.8S rRNA	28/7305	35/18723	8.71e-07	1.19e-05	28
GO:004343419	Oral cavity	OSCC	response to peptide hormone	208/7305	414/18723	1.83e-06	2.35e-05	208
GO:001969319	Oral cavity	OSCC	ribose phosphate metabolic process	199/7305	396/18723	2.97e-06	3.64e-05	199
GO:003286816	Oral cavity	OSCC	response to insulin	138/7305	264/18723	7.54e-06	8.15e-05	138
GO:000925919	Oral cavity	OSCC	ribonucleotide metabolic process	189/7305	385/18723	3.18e-05	2.87e-04	189
GO:00421804	Oral cavity	OSCC	cellular ketone metabolic process	111/7305	211/18723	3.94e-05	3.45e-04	111
GO:190370618	Oral cavity	OSCC	regulation of hemopoiesis	180/7305	367/18723	5.16e-05	4.30e-04	180
GO:000913217	Oral cavity	OSCC	nucleoside diphosphate metabolic process	70/7305	124/18723	6.03e-05	4.95e-04	70
GO:007259316	Oral cavity	OSCC	reactive oxygen species metabolic process	122/7305	239/18723	9.73e-05	7.34e-04	122
GO:004693917	Oral cavity	OSCC	nucleotide phosphorylation	58/7305	101/18723	1.33e-04	9.44e-04	58
GO:007252120	Oral cavity	OSCC	purine-containing compound metabolic process	199/7305	416/18723	1.34e-04	9.53e-04	199
GO:000915020	Oral cavity	OSCC	purine ribonucleotide metabolic process	178/7305	368/18723	1.45e-04	1.02e-03	178
GO:00160537	Oral cavity	OSCC	organic acid biosynthetic process	155/7305	316/18723	1.64e-04	1.13e-03	155
GO:00463947	Oral cavity	OSCC	carboxylic acid biosynthetic process	154/7305	314/18723	1.73e-04	1.19e-03	154
GO:000918518	Oral cavity	OSCC	ribonucleoside diphosphate metabolic process	60/7305	106/18723	1.78e-04	1.21e-03	60
GO:004346716	Oral cavity	OSCC	regulation of generation of precursor metabolites and energy	71/7305	130/18723	2.15e-04	1.41e-03	71
GO:00066317	Oral cavity	OSCC	fatty acid metabolic process	186/7305	390/18723	2.65e-04	1.69e-03	186
GO:000913519	Oral cavity	OSCC	purine nucleoside diphosphate metabolic process	58/7305	103/18723	2.73e-04	1.73e-03	58

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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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