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: EIF3K

Gene summary for EIF3K

Gene summary.

Gene information	Species	Human
	Gene symbol	EIF3K
	Gene ID	27335
	Gene name	eukaryotic translation initiation factor 3 subunit K
	Gene Alias	ARG134
	Cytomap	19q13.2
	Gene Type	protein-coding
	GO ID	GO:0001732
	UniProtAcc	K7ERF1

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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
27335	EIF3K	GSM4909277	Human	Breast	Precancer	2.20e-02	-6.78e-01	0.0177
27335	EIF3K	GSM4909280	Human	Breast	Precancer	3.60e-02	-4.83e-01	0.0305
27335	EIF3K	GSM4909282	Human	Breast	IDC	2.80e-16	4.08e-01	-0.0288
27335	EIF3K	GSM4909286	Human	Breast	IDC	1.16e-06	-5.46e-02	0.1081
27335	EIF3K	GSM4909294	Human	Breast	IDC	3.04e-04	1.86e-02	0.2022
27335	EIF3K	GSM4909296	Human	Breast	IDC	3.26e-12	3.74e-02	0.1524
27335	EIF3K	GSM4909297	Human	Breast	IDC	2.43e-26	-3.23e-01	0.1517
27335	EIF3K	GSM4909308	Human	Breast	IDC	1.27e-04	3.29e-01	0.158
27335	EIF3K	GSM4909311	Human	Breast	IDC	9.88e-57	-4.56e-01	0.1534
27335	EIF3K	GSM4909312	Human	Breast	IDC	1.10e-12	-1.45e-01	0.1552
27335	EIF3K	GSM4909313	Human	Breast	IDC	4.65e-05	-7.30e-02	0.0391
27335	EIF3K	GSM4909315	Human	Breast	IDC	1.34e-02	1.72e-01	0.21
27335	EIF3K	GSM4909319	Human	Breast	IDC	1.25e-65	-5.19e-01	0.1563
27335	EIF3K	GSM4909320	Human	Breast	IDC	1.07e-05	-1.17e-01	0.1575
27335	EIF3K	GSM4909321	Human	Breast	IDC	6.61e-14	-1.96e-02	0.1559
27335	EIF3K	ctrl6	Human	Breast	Precancer	1.62e-05	-4.04e-01	-0.0061
27335	EIF3K	brca2	Human	Breast	Precancer	3.73e-03	3.15e-02	-0.024
27335	EIF3K	brca10	Human	Breast	Precancer	4.43e-02	-2.27e-01	-0.0029
27335	EIF3K	M2	Human	Breast	IDC	3.46e-03	-3.37e-01	0.21
27335	EIF3K	NCCBC14	Human	Breast	DCIS	4.25e-14	-3.29e-01	0.2021

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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
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: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:00064172	Colorectum	MSS	regulation of translation	134/3467	468/18723	4.43e-08	2.38e-06	134
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: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:00226183	Colorectum	MSI-H	ribonucleoprotein complex assembly	62/1319	220/18723	7.13e-22	8.32e-19	62
GO:00718263	Colorectum	MSI-H	ribonucleoprotein complex subunit organization	63/1319	227/18723	8.08e-22	8.32e-19	63
GO:00226133	Colorectum	MSI-H	ribonucleoprotein complex biogenesis	95/1319	463/18723	1.04e-21	8.32e-19	95
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:00017323	Colorectum	MSI-H	formation of cytoplasmic translation initiation complex	12/1319	16/18723	1.99e-11	3.94e-09	12
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: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

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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

EIF3K

SNV

Missense_Mutation

c.403N>C

p.Glu135Gln

p.E135Q

Q9UBQ5

protein_coding

tolerated(0.05)

benign(0.22)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

EIF3K

SNV

Missense_Mutation

rs750097473

c.232N>G

p.Pro78Ala

p.P78A

Q9UBQ5

protein_coding

deleterious(0.01)

probably_damaging(0.975)

TCGA-AC-A3W6-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

EIF3K

SNV

Missense_Mutation

c.70N>C

p.Glu24Gln

p.E24Q

Q9UBQ5

protein_coding

tolerated(0.06)

benign(0.3)

TCGA-BH-A0HK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

EIF3K

SNV

Missense_Mutation

novel

c.577N>A

p.Glu193Lys

p.E193K

Q9UBQ5

protein_coding

deleterious(0)

probably_damaging(0.957)

TCGA-D8-A73U-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

EIF3K

SNV

Missense_Mutation

c.487N>A

p.Gly163Arg

p.G163R

Q9UBQ5

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AZ-4313-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

EIF3K

SNV

Missense_Mutation

novel

c.175G>C

p.Ala59Pro

p.A59P

Q9UBQ5

protein_coding

tolerated(0.26)

benign(0)

TCGA-AP-A1DR-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

EIF3K

SNV

Missense_Mutation

novel

c.188C>T

p.Thr63Ile

p.T63I

Q9UBQ5

protein_coding

tolerated(0.46)

benign(0.003)

TCGA-AX-A06F-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatin

EIF3K

SNV

Missense_Mutation

novel

c.208N>A

p.Leu70Met

p.L70M

Q9UBQ5

protein_coding

deleterious(0.03)

probably_damaging(0.966)

TCGA-B5-A1MX-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Hormone Therapy

megace

EIF3K

SNV

Missense_Mutation

rs764778412

c.299G>A

p.Arg100Gln

p.R100Q

Q9UBQ5

protein_coding

tolerated(0.63)

benign(0.018)

TCGA-BS-A0UF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

EIF3K

SNV

Missense_Mutation

c.416N>A

p.Arg139Gln

p.R139Q

Q9UBQ5

protein_coding

tolerated(0.1)

possibly_damaging(0.796)

TCGA-D1-A17Q-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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