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: FXYD3

Gene summary for FXYD3

Gene summary.

Gene information	Species	Human
	Gene symbol	FXYD3
	Gene ID	5349
	Gene name	FXYD domain containing ion transport regulator 3
	Gene Alias	MAT8
	Cytomap	19q13.12
	Gene Type	protein-coding
	GO ID	GO:0002028
	UniProtAcc	Q14802

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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
5349	FXYD3	GSM5353218_PA_PB1B_Pool_1_2_S74_L003	Human	Prostate	Tumor	9.56e-03	-8.71e-01	0.1479
5349	FXYD3	GSM5353220_PA_PB1B_Pool_3_S51_L002	Human	Prostate	Tumor	1.90e-03	-8.09e-01	0.1531
5349	FXYD3	GSM5353222_PA_PB2B_Pool_1_3_S52_L002	Human	Prostate	Tumor	2.27e-02	-3.69e-01	0.1608
5349	FXYD3	GSM5353225_PA_PR5196-1_Pool_1_2_3_S53_L002	Human	Prostate	Tumor	2.05e-06	-7.91e-01	0.1619
5349	FXYD3	GSM5353226_PA_PR5196-2_Pool_1_2_3_S54_L002	Human	Prostate	Tumor	9.46e-03	-7.70e-01	0.159
5349	FXYD3	GSM5353227_PA_PR5199-193K_Pool_1_2_3_S55_L002	Human	Prostate	Tumor	2.65e-09	-5.97e-01	0.1602
5349	FXYD3	GSM5353232_PA_PR5249_T1_S3_L001	Human	Prostate	Tumor	5.27e-03	-8.01e-01	0.1439
5349	FXYD3	GSM5353236_PA_PR5251_T1_S7_L001	Human	Prostate	Tumor	4.97e-04	-6.53e-01	0.1608
5349	FXYD3	GSM5353240_PA_PR5254_T1_S15_L001	Human	Prostate	Tumor	5.34e-03	-1.53e-01	0.1575
5349	FXYD3	GSM5353243_PA_PR5261_T1_S23_L002	Human	Prostate	Tumor	6.71e-20	-4.12e-01	0.1545
5349	FXYD3	GSM5353244_PA_PR5261_T2_S24_L002	Human	Prostate	Tumor	1.05e-11	-4.36e-01	0.1569
5349	FXYD3	GSM5353247_PA_PR5269_3_S27_L002	Human	Prostate	Tumor	2.60e-02	-8.23e-01	0.1532
5349	FXYD3	P1_S1_AK	Human	Skin	AK	4.70e-03	2.22e-01	-0.3399
5349	FXYD3	P2_S3_AK	Human	Skin	AK	3.38e-06	2.60e-01	-0.3287
5349	FXYD3	P4_S8_cSCC	Human	Skin	cSCC	8.31e-25	5.41e-01	-0.3095
5349	FXYD3	P5_S10_cSCC	Human	Skin	cSCC	2.39e-51	8.75e-01	-0.299
5349	FXYD3	P1_cSCC	Human	Skin	cSCC	1.62e-89	4.13e+00	0.0292
5349	FXYD3	P2_cSCC	Human	Skin	cSCC	6.89e-81	2.79e+00	-0.024
5349	FXYD3	P4_cSCC	Human	Skin	cSCC	2.43e-94	3.03e+00	-0.00290000000000005
5349	FXYD3	P10_cSCC	Human	Skin	cSCC	1.45e-68	2.52e+00	0.1017

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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
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
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

∗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:00109596	Breast	Precancer	regulation of metal ion transport	37/1080	406/18723	4.07e-03	3.22e-02	37
GO:00228985	Breast	Precancer	regulation of transmembrane transporter activity	27/1080	278/18723	5.72e-03	4.11e-02	27
GO:001095913	Breast	IDC	regulation of metal ion transport	52/1434	406/18723	1.76e-04	2.97e-03	52
GO:002289812	Breast	IDC	regulation of transmembrane transporter activity	36/1434	278/18723	1.35e-03	1.40e-02	36
GO:00324125	Breast	IDC	regulation of ion transmembrane transporter activity	33/1434	267/18723	4.38e-03	3.40e-02	33
GO:00324096	Breast	IDC	regulation of transporter activity	37/1434	310/18723	4.77e-03	3.66e-02	37
GO:001095921	Breast	DCIS	regulation of metal ion transport	50/1390	406/18723	2.86e-04	4.22e-03	50
GO:002289822	Breast	DCIS	regulation of transmembrane transporter activity	35/1390	278/18723	1.50e-03	1.51e-02	35
GO:003241212	Breast	DCIS	regulation of ion transmembrane transporter activity	32/1390	267/18723	4.97e-03	3.72e-02	32
GO:003240912	Breast	DCIS	regulation of transporter activity	36/1390	310/18723	5.05e-03	3.74e-02	36
GO:19023059	Cervix	CC	regulation of sodium ion transmembrane transport	19/2311	68/18723	4.21e-04	4.25e-03	19
GO:00020288	Cervix	CC	regulation of sodium ion transport	21/2311	90/18723	2.71e-03	1.85e-02	21
GO:20006498	Cervix	CC	regulation of sodium ion transmembrane transporter activity	15/2311	58/18723	3.75e-03	2.38e-02	15
GO:0002028	Colorectum	AD	regulation of sodium ion transport	36/3918	90/18723	2.89e-05	5.37e-04	36
GO:1902305	Colorectum	AD	regulation of sodium ion transmembrane transport	27/3918	68/18723	3.19e-04	3.80e-03	27
GO:2000649	Colorectum	AD	regulation of sodium ion transmembrane transporter activity	23/3918	58/18723	8.82e-04	8.53e-03	23
GO:0015698	Colorectum	AD	inorganic anion transport	52/3918	180/18723	6.83e-03	4.22e-02	52
GO:00020281	Colorectum	SER	regulation of sodium ion transport	28/2897	90/18723	1.45e-04	2.86e-03	28
GO:19023051	Colorectum	SER	regulation of sodium ion transmembrane transport	21/2897	68/18723	1.05e-03	1.22e-02	21
GO:20006491	Colorectum	SER	regulation of sodium ion transmembrane transporter activity	18/2897	58/18723	2.18e-03	2.11e-02	18

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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

FXYD3

SNV

Missense_Mutation

c.292G>C

p.Gly98Arg

p.G98R

Q14802

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AC-A2BK-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

cytoxan

FXYD3

SNV

Missense_Mutation

c.203N>G

p.Phe68Cys

p.F68C

Q14802

protein_coding

deleterious(0.01)

possibly_damaging(0.753)

TCGA-C8-A26Z-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

FXYD3

SNV

Missense_Mutation

novel

c.310G>T

p.Val104Phe

p.V104F

Q14802

protein_coding

deleterious(0)

possibly_damaging(0.868)

TCGA-EA-A3HU-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

FXYD3

SNV

Missense_Mutation

novel

c.323T>C

p.Met108Thr

p.M108T

Q14802

protein_coding

deleterious(0.04)

benign(0.03)

TCGA-CA-6717-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Chemotherapy

oxaliplatin

FXYD3

SNV

Missense_Mutation

novel

c.128C>T

p.Ala43Val

p.A43V

Q14802

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(0.915)

TCGA-F5-6814-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

FXYD3

SNV

Missense_Mutation

novel

c.145C>T

p.Leu49Phe

p.L49F

Q14802

protein_coding

tolerated(0.24)

probably_damaging(0.974)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

FXYD3

SNV

Missense_Mutation

novel

c.257N>A

p.Pro86His

p.P86H

Q14802

protein_coding

deleterious(0.01)

probably_damaging(0.999)

TCGA-AJ-A5DW-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

FXYD3

SNV

Missense_Mutation

c.274N>T

p.His92Tyr

p.H92Y

Q14802

protein_coding

tolerated(0.17)

benign(0.013)

TCGA-AX-A1C4-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

FXYD3

SNV

Missense_Mutation

novel

c.257N>A

p.Pro86His

p.P86H

Q14802

protein_coding

deleterious(0.01)

probably_damaging(0.999)

TCGA-AX-A2HC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

FXYD3

SNV

Missense_Mutation

novel

c.248A>C

p.Lys83Thr

p.K83T

Q14802

protein_coding

deleterious(0.02)

probably_damaging(0.976)

TCGA-BK-A6W3-01

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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