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: FXYD5

Gene summary for FXYD5

Gene summary.

Gene information	Species	Human
	Gene symbol	FXYD5
	Gene ID	53827
	Gene name	FXYD domain containing ion transport regulator 5
	Gene Alias	DYSAD
	Cytomap	19q13.12
	Gene Type	protein-coding
	GO ID	GO:0002028
	UniProtAcc	Q96DB9

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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
53827	FXYD5	GSM4909282	Human	Breast	IDC	1.60e-04	2.66e-01	-0.0288
53827	FXYD5	GSM4909286	Human	Breast	IDC	5.65e-26	-5.06e-01	0.1081
53827	FXYD5	GSM4909287	Human	Breast	IDC	3.78e-05	2.48e-01	0.2057
53827	FXYD5	GSM4909290	Human	Breast	IDC	1.21e-02	-3.46e-01	0.2096
53827	FXYD5	GSM4909291	Human	Breast	IDC	4.84e-09	-4.60e-01	0.1753
53827	FXYD5	GSM4909294	Human	Breast	IDC	1.68e-20	-4.72e-01	0.2022
53827	FXYD5	GSM4909295	Human	Breast	IDC	8.17e-11	5.05e-01	0.0898
53827	FXYD5	GSM4909296	Human	Breast	IDC	1.61e-09	2.33e-01	0.1524
53827	FXYD5	GSM4909297	Human	Breast	IDC	2.83e-10	-1.41e-01	0.1517
53827	FXYD5	GSM4909298	Human	Breast	IDC	6.27e-09	-3.97e-01	0.1551
53827	FXYD5	GSM4909301	Human	Breast	IDC	4.38e-03	-3.00e-01	0.1577
53827	FXYD5	GSM4909302	Human	Breast	IDC	8.85e-07	-3.58e-01	0.1545
53827	FXYD5	GSM4909304	Human	Breast	IDC	9.00e-22	-4.88e-01	0.1636
53827	FXYD5	GSM4909305	Human	Breast	IDC	2.15e-03	3.19e-01	0.0436
53827	FXYD5	GSM4909309	Human	Breast	IDC	1.19e-06	2.63e-01	0.0483
53827	FXYD5	GSM4909311	Human	Breast	IDC	1.93e-20	-3.13e-01	0.1534
53827	FXYD5	GSM4909312	Human	Breast	IDC	5.00e-08	-2.62e-01	0.1552
53827	FXYD5	GSM4909313	Human	Breast	IDC	1.23e-06	2.33e-01	0.0391
53827	FXYD5	GSM4909319	Human	Breast	IDC	2.22e-23	-4.89e-01	0.1563
53827	FXYD5	GSM4909320	Human	Breast	IDC	1.29e-09	-1.68e-01	0.1575

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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
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
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:00224079	Breast	Precancer	regulation of cell-cell adhesion	45/1080	448/18723	2.12e-04	3.30e-03	45
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:002240712	Breast	IDC	regulation of cell-cell adhesion	55/1434	448/18723	3.43e-04	5.07e-03	55
GO:002289812	Breast	IDC	regulation of transmembrane transporter activity	36/1434	278/18723	1.35e-03	1.40e-02	36
GO:00071625	Breast	IDC	negative regulation of cell adhesion	37/1434	303/18723	3.27e-03	2.75e-02	37
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:002240722	Breast	DCIS	regulation of cell-cell adhesion	56/1390	448/18723	8.53e-05	1.61e-03	56
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:000716212	Breast	DCIS	negative regulation of cell adhesion	36/1390	303/18723	3.49e-03	2.90e-02	36
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:002240710	Cervix	CC	regulation of cell-cell adhesion	103/2311	448/18723	1.78e-10	2.87e-08	103
GO:00071626	Cervix	CC	negative regulation of cell adhesion	72/2311	303/18723	2.36e-08	1.70e-06	72
GO:00224084	Cervix	CC	negative regulation of cell-cell adhesion	48/2311	196/18723	1.99e-06	6.18e-05	48
GO:19023059	Cervix	CC	regulation of sodium ion transmembrane transport	19/2311	68/18723	4.21e-04	4.25e-03	19
GO:00300337	Cervix	CC	microvillus assembly	7/2311	16/18723	1.79e-03	1.34e-02	7

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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

FXYD5

SNV

Missense_Mutation

c.216N>T

p.Gln72His

p.Q72H

protein_coding

tolerated(0.1)

benign(0.143)

TCGA-D8-A1JB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

FXYD5

SNV

Missense_Mutation

rs140956604

c.134N>A

p.Arg45Gln

p.R45Q

protein_coding

tolerated(0.7)

benign(0)

TCGA-E9-A1RF-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

tamoxiphen

FXYD5

insertion

In_Frame_Ins

novel

c.470_471insCAT

p.Ile160dup

p.I160dup

protein_coding

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

FXYD5

deletion

Frame_Shift_Del

c.360delN

p.Gln122ArgfsTer59

p.Q122Rfs*59

protein_coding

TCGA-AN-A0AR-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

FXYD5

deletion

Frame_Shift_Del

novel

c.447delN

p.Ala150GlnfsTer31

p.A150Qfs*31

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

FXYD5

SNV

Missense_Mutation

novel

c.565N>T

p.Pro189Ser

p.P189S

protein_coding

tolerated_low_confidence(0.36)

benign(0.058)

TCGA-AA-A01V-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

FXYD5

SNV

Missense_Mutation

c.229C>A

p.Gln77Lys

p.Q77K

protein_coding

tolerated(0.29)

benign(0.007)

TCGA-CK-6751-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

FXYD5

SNV

Missense_Mutation

novel

c.228G>T

p.Gln76His

p.Q76H

protein_coding

tolerated(0.11)

possibly_damaging(0.713)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

FXYD5

SNV

Missense_Mutation

rs750600377

c.83N>T

p.Thr28Met

p.T28M

protein_coding

deleterious(0)

probably_damaging(0.927)

TCGA-AJ-A2QO-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

FXYD5

SNV

Missense_Mutation

novel

c.148G>A

p.Val50Ile

p.V50I

protein_coding

tolerated(0.26)

benign(0)

TCGA-AP-A1DK-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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