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: EIF3A

Gene summary for EIF3A

Gene summary.

Gene information	Species	Human
	Gene symbol	EIF3A
	Gene ID	8661
	Gene name	eukaryotic translation initiation factor 3 subunit A
	Gene Alias	EIF3
	Cytomap	10q26.11
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	Q14152

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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
8661	EIF3A	male-WTA	Human	Thyroid	PTC	8.69e-64	3.87e-01	0.1037
8661	EIF3A	nodule-WTA	Human	Thyroid	goiters	3.34e-02	2.39e-01	0.0534
8661	EIF3A	PTC01	Human	Thyroid	PTC	3.71e-18	6.86e-01	0.1899
8661	EIF3A	PTC03	Human	Thyroid	PTC	6.63e-06	6.61e-01	0.1784
8661	EIF3A	PTC04	Human	Thyroid	PTC	1.21e-25	9.01e-01	0.1927
8661	EIF3A	PTC05	Human	Thyroid	PTC	6.57e-28	1.56e+00	0.2065
8661	EIF3A	PTC06	Human	Thyroid	PTC	5.03e-62	1.82e+00	0.2057
8661	EIF3A	PTC07	Human	Thyroid	PTC	1.31e-62	1.20e+00	0.2044
8661	EIF3A	ATC08	Human	Thyroid	ATC	4.93e-06	-7.85e-02	0.0541
8661	EIF3A	ATC09	Human	Thyroid	ATC	4.53e-11	3.42e-01	0.2871
8661	EIF3A	ATC11	Human	Thyroid	ATC	9.12e-06	1.17e+00	0.3386
8661	EIF3A	ATC12	Human	Thyroid	ATC	2.96e-22	9.59e-01	0.34
8661	EIF3A	ATC13	Human	Thyroid	ATC	3.82e-50	1.49e+00	0.34
8661	EIF3A	ATC1	Human	Thyroid	ATC	5.26e-09	4.38e-01	0.2878
8661	EIF3A	ATC2	Human	Thyroid	ATC	7.93e-19	2.21e+00	0.34
8661	EIF3A	ATC3	Human	Thyroid	ATC	3.40e-13	1.01e+00	0.338
8661	EIF3A	ATC4	Human	Thyroid	ATC	6.48e-32	1.28e+00	0.34
8661	EIF3A	ATC5	Human	Thyroid	ATC	1.50e-48	1.64e+00	0.34

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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
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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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:0016032	Colorectum	AD	viral process	168/3918	415/18723	4.67e-20	3.66e-17	168
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:0019080	Colorectum	AD	viral gene expression	42/3918	94/18723	1.90e-07	8.02e-06	42
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:0075522	Colorectum	AD	IRES-dependent viral translational initiation	8/3918	11/18723	3.26e-04	3.85e-03	8
GO:0019081	Colorectum	AD	viral translation	10/3918	16/18723	3.64e-04	4.22e-03	10
GO:0043409	Colorectum	AD	negative regulation of MAPK cascade	57/3918	180/18723	4.61e-04	5.14e-03	57
GO:00021812	Colorectum	MSS	cytoplasmic translation	108/3467	148/18723	1.78e-47	1.11e-43	108
GO:00160322	Colorectum	MSS	viral process	157/3467	415/18723	7.94e-21	6.19e-18	157
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:00190802	Colorectum	MSS	viral gene expression	41/3467	94/18723	1.74e-08	9.85e-07	41
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

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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

EIF3A

SNV

Missense_Mutation

novel

c.2263N>A

p.Glu755Lys

p.E755K

Q14152

protein_coding

tolerated(0.27)

benign(0.19)

TCGA-A2-A0CR-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

EIF3A

SNV

Missense_Mutation

rs771425860

c.3593N>T

p.Ser1198Leu

p.S1198L

Q14152

protein_coding

tolerated_low_confidence(0.07)

benign(0.011)

TCGA-BH-A0AW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

EIF3A

SNV

Missense_Mutation

c.4145G>A

p.Arg1382His

p.R1382H

Q14152

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.991)

TCGA-BH-A18L-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

EIF3A

SNV

Missense_Mutation

novel

c.3472N>G

p.Pro1158Ala

p.P1158A

Q14152

protein_coding

tolerated_low_confidence(0.2)

benign(0.138)

TCGA-C8-A3M7-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

EIF3A

SNV

Missense_Mutation

novel

c.1749G>C

p.Glu583Asp

p.E583D

Q14152

protein_coding

deleterious(0.01)

probably_damaging(0.97)

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

EIF3A

SNV

Missense_Mutation

novel

c.2906N>C

p.Arg969Thr

p.R969T

Q14152

protein_coding

deleterious(0.02)

possibly_damaging(0.628)

TCGA-OL-A5RW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

EIF3A

insertion

In_Frame_Ins

novel

c.1994_1995insAAATAATGCCGCTCCAGTTCC

p.Asp665delinsGluAsnAsnAlaAlaProValPro

p.D665delinsENNAAPVP

Q14152

protein_coding

TCGA-A2-A0EO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

EIF3A

insertion

Frame_Shift_Ins

novel

c.1617_1618insAAGA

p.Ala540LysfsTer21

p.A540Kfs*21

Q14152

protein_coding

TCGA-A8-A07R-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Ancillary

zoledronic

EIF3A

insertion

Frame_Shift_Ins

novel

c.1615_1616insTGGGTGC

p.Pro539LeufsTer23

p.P539Lfs*23

Q14152

protein_coding

TCGA-A8-A07R-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Ancillary

zoledronic

EIF3A

deletion

Frame_Shift_Del

novel

c.2944delG

p.Ala982GlnfsTer191

p.A982Qfs*191

Q14152

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

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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
8661	EIF3A	NA		Platinum compounds
8661	EIF3A	NA		carboplatin	CARBOPLATIN	23127338
8661	EIF3A	NA		cisplatin	CISPLATIN	23127338

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