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: SLC9A3R1

Gene summary for SLC9A3R1

Gene summary.

Gene information	Species	Human
	Gene symbol	SLC9A3R1
	Gene ID	9368
	Gene name	SLC9A3 regulator 1
	Gene Alias	EBP50
	Cytomap	17q25.1
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	O14745

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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
9368	SLC9A3R1	GSM4909282	Human	Breast	IDC	1.16e-07	3.63e-01	-0.0288
9368	SLC9A3R1	GSM4909285	Human	Breast	IDC	6.64e-31	7.57e-01	0.21
9368	SLC9A3R1	GSM4909289	Human	Breast	IDC	4.92e-10	7.29e-01	0.1064
9368	SLC9A3R1	GSM4909290	Human	Breast	IDC	1.27e-03	2.68e-01	0.2096
9368	SLC9A3R1	GSM4909291	Human	Breast	IDC	1.78e-44	9.91e-01	0.1753
9368	SLC9A3R1	GSM4909293	Human	Breast	IDC	7.24e-56	9.35e-01	0.1581
9368	SLC9A3R1	GSM4909296	Human	Breast	IDC	6.01e-04	2.16e-02	0.1524
9368	SLC9A3R1	GSM4909297	Human	Breast	IDC	1.17e-03	9.41e-03	0.1517
9368	SLC9A3R1	GSM4909298	Human	Breast	IDC	7.99e-03	2.92e-01	0.1551
9368	SLC9A3R1	GSM4909301	Human	Breast	IDC	2.34e-24	6.60e-01	0.1577
9368	SLC9A3R1	GSM4909304	Human	Breast	IDC	4.70e-07	3.64e-01	0.1636
9368	SLC9A3R1	GSM4909305	Human	Breast	IDC	7.32e-08	3.71e-01	0.0436
9368	SLC9A3R1	GSM4909306	Human	Breast	IDC	1.19e-09	4.45e-01	0.1564
9368	SLC9A3R1	GSM4909307	Human	Breast	IDC	1.47e-06	3.81e-01	0.1569
9368	SLC9A3R1	GSM4909308	Human	Breast	IDC	4.25e-22	5.19e-01	0.158
9368	SLC9A3R1	GSM4909311	Human	Breast	IDC	1.53e-26	1.70e-01	0.1534
9368	SLC9A3R1	GSM4909312	Human	Breast	IDC	1.45e-20	4.45e-01	0.1552
9368	SLC9A3R1	GSM4909313	Human	Breast	IDC	1.38e-09	4.31e-01	0.0391
9368	SLC9A3R1	GSM4909317	Human	Breast	IDC	4.37e-47	9.13e-01	0.1355
9368	SLC9A3R1	GSM4909318	Human	Breast	IDC	1.28e-15	9.75e-01	0.2031

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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
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:00971939	Breast	Precancer	intrinsic apoptotic signaling pathway	59/1080	288/18723	8.07e-18	3.60e-15	59
GO:20012339	Breast	Precancer	regulation of apoptotic signaling pathway	65/1080	356/18723	7.70e-17	3.17e-14	65
GO:20012429	Breast	Precancer	regulation of intrinsic apoptotic signaling pathway	41/1080	164/18723	6.48e-16	2.31e-13	41
GO:19026008	Breast	Precancer	proton transmembrane transport	39/1080	157/18723	4.18e-15	1.18e-12	39
GO:20012445	Breast	Precancer	positive regulation of intrinsic apoptotic signaling pathway	17/1080	58/18723	1.59e-08	1.12e-06	17
GO:20012356	Breast	Precancer	positive regulation of apoptotic signaling pathway	24/1080	126/18723	1.98e-07	1.01e-05	24
GO:00487329	Breast	Precancer	gland development	49/1080	436/18723	6.11e-06	1.73e-04	49
GO:00702933	Breast	Precancer	renal absorption	6/1080	17/18723	2.59e-04	3.83e-03	6
GO:00085445	Breast	Precancer	epidermis development	35/1080	324/18723	2.71e-04	3.96e-03	35
GO:00099136	Breast	Precancer	epidermal cell differentiation	23/1080	202/18723	1.43e-03	1.50e-02	23
GO:00434912	Breast	Precancer	protein kinase B signaling	23/1080	211/18723	2.53e-03	2.30e-02	23
GO:00158336	Breast	Precancer	peptide transport	27/1080	264/18723	2.84e-03	2.49e-02	27
GO:00347673	Breast	Precancer	positive regulation of ion transmembrane transport	19/1080	167/18723	3.60e-03	2.98e-02	19
GO:00071638	Breast	Precancer	establishment or maintenance of cell polarity	23/1080	218/18723	3.82e-03	3.06e-02	23
GO:00109596	Breast	Precancer	regulation of metal ion transport	37/1080	406/18723	4.07e-03	3.22e-02	37
GO:00020649	Breast	Precancer	epithelial cell development	23/1080	220/18723	4.28e-03	3.35e-02	23
GO:00228985	Breast	Precancer	regulation of transmembrane transporter activity	27/1080	278/18723	5.72e-03	4.11e-02	27
GO:00226049	Breast	Precancer	regulation of cell morphogenesis	29/1080	309/18723	6.88e-03	4.67e-02	29
GO:200123314	Breast	IDC	regulation of apoptotic signaling pathway	82/1434	356/18723	6.27e-20	5.93e-17	82
GO:009719314	Breast	IDC	intrinsic apoptotic signaling pathway	69/1434	288/18723	6.32e-18	2.99e-15	69

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0513018	Breast	Precancer	Pathogenic Escherichia coli infection	38/684	197/8465	3.12e-07	5.81e-06	4.45e-06	38
hsa0453018	Breast	Precancer	Tight junction	31/684	169/8465	1.13e-05	1.26e-04	9.64e-05	31
hsa0513019	Breast	Precancer	Pathogenic Escherichia coli infection	38/684	197/8465	3.12e-07	5.81e-06	4.45e-06	38
hsa0453019	Breast	Precancer	Tight junction	31/684	169/8465	1.13e-05	1.26e-04	9.64e-05	31
hsa0453024	Breast	IDC	Tight junction	38/867	169/8465	2.07e-06	3.20e-05	2.39e-05	38
hsa0513024	Breast	IDC	Pathogenic Escherichia coli infection	42/867	197/8465	2.66e-06	3.92e-05	2.94e-05	42
hsa0453034	Breast	IDC	Tight junction	38/867	169/8465	2.07e-06	3.20e-05	2.39e-05	38
hsa0513034	Breast	IDC	Pathogenic Escherichia coli infection	42/867	197/8465	2.66e-06	3.92e-05	2.94e-05	42
hsa0513043	Breast	DCIS	Pathogenic Escherichia coli infection	42/846	197/8465	1.40e-06	2.15e-05	1.59e-05	42
hsa0453044	Breast	DCIS	Tight junction	37/846	169/8465	3.07e-06	4.20e-05	3.09e-05	37
hsa0513053	Breast	DCIS	Pathogenic Escherichia coli infection	42/846	197/8465	1.40e-06	2.15e-05	1.59e-05	42
hsa0453054	Breast	DCIS	Tight junction	37/846	169/8465	3.07e-06	4.20e-05	3.09e-05	37
hsa04530	Colorectum	AD	Tight junction	76/2092	169/8465	5.49e-09	9.69e-08	6.18e-08	76
hsa05130	Colorectum	AD	Pathogenic Escherichia coli infection	79/2092	197/8465	1.05e-06	1.36e-05	8.65e-06	79
hsa04928	Colorectum	AD	Parathyroid hormone synthesis, secretion and action	38/2092	106/8465	6.60e-03	2.77e-02	1.76e-02	38
hsa045301	Colorectum	AD	Tight junction	76/2092	169/8465	5.49e-09	9.69e-08	6.18e-08	76
hsa051301	Colorectum	AD	Pathogenic Escherichia coli infection	79/2092	197/8465	1.05e-06	1.36e-05	8.65e-06	79
hsa049281	Colorectum	AD	Parathyroid hormone synthesis, secretion and action	38/2092	106/8465	6.60e-03	2.77e-02	1.76e-02	38
hsa045302	Colorectum	SER	Tight junction	59/1580	169/8465	3.24e-07	5.98e-06	4.34e-06	59
hsa051302	Colorectum	SER	Pathogenic Escherichia coli infection	60/1580	197/8465	3.63e-05	4.31e-04	3.13e-04	60

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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

SLC9A3R1

SNV

Missense_Mutation

rs775971197

c.560N>G

p.Pro187Arg

p.P187R

O14745

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SLC9A3R1

SNV

Missense_Mutation

novel

c.592C>G

p.Arg198Gly

p.R198G

O14745

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-AC-A62V-01

Breast

breast invasive carcinoma

Male

<65

III/IV

Targeted Molecular therapy

denosumab

SLC9A3R1

SNV

Missense_Mutation

novel

c.1073T>C

p.Leu358Pro

p.L358P

O14745

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-B6-A0IB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

SLC9A3R1

SNV

Missense_Mutation

novel

c.112N>C

p.Tyr38His

p.Y38H

O14745

protein_coding

deleterious(0)

possibly_damaging(0.886)

TCGA-JL-A3YW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SLC9A3R1

SNV

Missense_Mutation

c.548A>T

p.Asp183Val

p.D183V

O14745

protein_coding

deleterious(0)

probably_damaging(0.989)

TCGA-AA-3715-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

SLC9A3R1

SNV

Missense_Mutation

novel

c.789N>T

p.Glu263Asp

p.E263D

O14745

protein_coding

tolerated(0.55)

benign(0.001)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

SLC9A3R1

SNV

Missense_Mutation

novel

c.766N>T

p.Pro256Ser

p.P256S

O14745

protein_coding

deleterious(0.01)

possibly_damaging(0.858)

TCGA-AP-A1DK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

SLC9A3R1

SNV

Missense_Mutation

c.454N>T

p.Pro152Ser

p.P152S

O14745

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AX-A0J1-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

SLC9A3R1

SNV

Missense_Mutation

c.782N>G

p.Asn261Ser

p.N261S

O14745

protein_coding

tolerated(0.07)

benign(0.059)

TCGA-BS-A0V8-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

SLC9A3R1

SNV

Missense_Mutation

novel

c.624N>T

p.Glu208Asp

p.E208D

O14745

protein_coding

deleterious(0.03)

benign(0.137)

TCGA-DF-A2KN-01

Endometrium

uterine corpus endometrioid carcinoma

Female

Unknown

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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