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: ATP2B1

Gene summary for ATP2B1

Gene summary.

Gene information	Species	Human
	Gene symbol	ATP2B1
	Gene ID	490
	Gene name	ATPase plasma membrane Ca2+ transporting 1
	Gene Alias	PMCA1
	Cytomap	12q21.33
	Gene Type	protein-coding
	GO ID	GO:0001503
	UniProtAcc	P20020

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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
490	ATP2B1	HTA11_3410_2000001011	Human	Colorectum	AD	3.66e-10	-5.06e-01	0.0155
490	ATP2B1	HTA11_347_2000001011	Human	Colorectum	AD	9.26e-04	3.83e-01	-0.1954
490	ATP2B1	HTA11_866_3004761011	Human	Colorectum	AD	2.43e-05	-4.62e-01	0.096
490	ATP2B1	HTA11_10711_2000001011	Human	Colorectum	AD	5.50e-03	-4.78e-01	0.0338
490	ATP2B1	HTA11_7696_3000711011	Human	Colorectum	AD	3.84e-10	-3.97e-01	0.0674
490	ATP2B1	HTA11_99999974143_84620	Human	Colorectum	MSS	2.29e-23	-6.11e-01	0.3005
490	ATP2B1	F007	Human	Colorectum	FAP	3.31e-02	-3.57e-01	0.1176
490	ATP2B1	A002-C-010	Human	Colorectum	FAP	1.48e-05	-3.30e-01	0.242
490	ATP2B1	A001-C-207	Human	Colorectum	FAP	2.44e-05	-3.54e-01	0.1278
490	ATP2B1	A015-C-203	Human	Colorectum	FAP	2.92e-27	-4.74e-01	-0.1294
490	ATP2B1	A015-C-204	Human	Colorectum	FAP	4.30e-03	-2.75e-01	-0.0228
490	ATP2B1	A014-C-040	Human	Colorectum	FAP	1.07e-03	-4.92e-01	-0.1184
490	ATP2B1	A002-C-201	Human	Colorectum	FAP	7.38e-13	-4.49e-01	0.0324
490	ATP2B1	A002-C-203	Human	Colorectum	FAP	4.34e-13	-3.97e-01	0.2786
490	ATP2B1	A001-C-119	Human	Colorectum	FAP	2.90e-07	-5.23e-01	-0.1557
490	ATP2B1	A001-C-108	Human	Colorectum	FAP	1.37e-16	-3.93e-01	-0.0272
490	ATP2B1	A002-C-205	Human	Colorectum	FAP	1.47e-17	-4.84e-01	-0.1236
490	ATP2B1	A001-C-104	Human	Colorectum	FAP	9.36e-06	-2.44e-01	0.0184
490	ATP2B1	A015-C-005	Human	Colorectum	FAP	4.03e-05	-4.06e-01	-0.0336
490	ATP2B1	A015-C-006	Human	Colorectum	FAP	6.51e-11	-3.75e-01	-0.0994

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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
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:005138425	Skin	AK	response to glucocorticoid	33/1910	148/18723	1.20e-05	2.46e-04	33
GO:004343425	Skin	AK	response to peptide hormone	69/1910	414/18723	2.87e-05	4.98e-04	69
GO:003166824	Skin	AK	cellular response to extracellular stimulus	46/1910	246/18723	3.67e-05	6.11e-04	46
GO:007137517	Skin	AK	cellular response to peptide hormone stimulus	52/1910	290/18723	3.86e-05	6.35e-04	52
GO:190165320	Skin	AK	cellular response to peptide	61/1910	359/18723	4.60e-05	7.21e-04	61
GO:003286919	Skin	AK	cellular response to insulin stimulus	39/1910	203/18723	7.61e-05	1.07e-03	39
GO:007138510	Skin	AK	cellular response to glucocorticoid stimulus	16/1910	56/18723	1.02e-04	1.34e-03	16
GO:000926620	Skin	AK	response to temperature stimulus	34/1910	178/18723	2.38e-04	2.61e-03	34
GO:007138410	Skin	AK	cellular response to corticosteroid stimulus	16/1910	61/18723	3.03e-04	3.12e-03	16
GO:003166727	Skin	AK	response to nutrient levels	72/1910	474/18723	3.74e-04	3.63e-03	72
GO:003166924	Skin	AK	cellular response to nutrient levels	38/1910	215/18723	5.37e-04	4.86e-03	38
GO:003286819	Skin	AK	response to insulin	43/1910	264/18723	1.37e-03	1.02e-02	43
GO:19016557	Skin	AK	cellular response to ketone	20/1910	96/18723	1.46e-03	1.06e-02	20
GO:000758415	Skin	AK	response to nutrient	31/1910	174/18723	1.46e-03	1.06e-02	31
GO:009730526	Skin	AK	response to alcohol	41/1910	253/18723	1.92e-03	1.31e-02	41
GO:00030129	Skin	AK	muscle system process	64/1910	452/18723	4.32e-03	2.52e-02	64
GO:00302784	Skin	AK	regulation of ossification	21/1910	115/18723	5.91e-03	3.20e-02	21
GO:009025714	Skin	AK	regulation of muscle system process	38/1910	252/18723	9.21e-03	4.52e-02	38
GO:004854529	Skin	cSCC	response to steroid hormone	135/4864	339/18723	1.34e-08	4.09e-07	135
GO:007149628	Skin	cSCC	cellular response to external stimulus	125/4864	320/18723	1.63e-07	3.65e-06	125

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa04961	Colorectum	AD	Endocrine and other factor-regulated calcium reabsorption	24/2092	53/8465	8.49e-04	5.93e-03	3.78e-03	24
hsa04972	Colorectum	AD	Pancreatic secretion	36/2092	102/8465	1.06e-02	3.98e-02	2.54e-02	36
hsa049611	Colorectum	AD	Endocrine and other factor-regulated calcium reabsorption	24/2092	53/8465	8.49e-04	5.93e-03	3.78e-03	24
hsa049721	Colorectum	AD	Pancreatic secretion	36/2092	102/8465	1.06e-02	3.98e-02	2.54e-02	36
hsa049614	Colorectum	MSS	Endocrine and other factor-regulated calcium reabsorption	24/1875	53/8465	1.49e-04	1.24e-03	7.61e-04	24
hsa049724	Colorectum	MSS	Pancreatic secretion	33/1875	102/8465	1.09e-02	3.75e-02	2.30e-02	33
hsa049615	Colorectum	MSS	Endocrine and other factor-regulated calcium reabsorption	24/1875	53/8465	1.49e-04	1.24e-03	7.61e-04	24
hsa049725	Colorectum	MSS	Pancreatic secretion	33/1875	102/8465	1.09e-02	3.75e-02	2.30e-02	33
hsa049726	Colorectum	FAP	Pancreatic secretion	34/1404	102/8465	2.43e-05	2.78e-04	1.69e-04	34
hsa049616	Colorectum	FAP	Endocrine and other factor-regulated calcium reabsorption	18/1404	53/8465	1.52e-03	7.94e-03	4.83e-03	18
hsa040222	Colorectum	FAP	cGMP-PKG signaling pathway	42/1404	167/8465	2.84e-03	1.27e-02	7.70e-03	42
hsa04261	Colorectum	FAP	Adrenergic signaling in cardiomyocytes	38/1404	154/8465	6.16e-03	2.34e-02	1.42e-02	38
hsa04024	Colorectum	FAP	cAMP signaling pathway	51/1404	225/8465	1.02e-02	3.68e-02	2.24e-02	51
hsa04970	Colorectum	FAP	Salivary secretion	24/1404	93/8465	1.52e-02	4.99e-02	3.03e-02	24
hsa04925	Colorectum	FAP	Aldosterone synthesis and secretion	25/1404	98/8465	1.55e-02	4.99e-02	3.04e-02	25
hsa049727	Colorectum	FAP	Pancreatic secretion	34/1404	102/8465	2.43e-05	2.78e-04	1.69e-04	34
hsa049617	Colorectum	FAP	Endocrine and other factor-regulated calcium reabsorption	18/1404	53/8465	1.52e-03	7.94e-03	4.83e-03	18
hsa040223	Colorectum	FAP	cGMP-PKG signaling pathway	42/1404	167/8465	2.84e-03	1.27e-02	7.70e-03	42
hsa042611	Colorectum	FAP	Adrenergic signaling in cardiomyocytes	38/1404	154/8465	6.16e-03	2.34e-02	1.42e-02	38
hsa040241	Colorectum	FAP	cAMP signaling pathway	51/1404	225/8465	1.02e-02	3.68e-02	2.24e-02	51

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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

ATP2B1

SNV

Missense_Mutation

novel

c.2065G>A

p.Glu689Lys

p.E689K

P20020

protein_coding

deleterious(0)

probably_damaging(0.991)

TCGA-A2-A0CL-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

ATP2B1

SNV

Missense_Mutation

c.1486N>A

p.His496Asn

p.H496N

P20020

protein_coding

deleterious(0.03)

benign(0.201)

TCGA-A2-A0CX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

ATP2B1

SNV

Missense_Mutation

c.763N>A

p.Asp255Asn

p.D255N

P20020

protein_coding

tolerated(0.15)

benign(0.403)

TCGA-A2-A0SY-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

arimidex

ATP2B1

SNV

Missense_Mutation

c.2063C>A

p.Pro688His

p.P688H

P20020

protein_coding

deleterious(0.01)

probably_damaging(0.999)

TCGA-A2-A25A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Cytoxan

ATP2B1

SNV

Missense_Mutation

novel

c.1790N>A

p.Arg597Gln

p.R597Q

P20020

protein_coding

deleterious(0.03)

probably_damaging(0.99)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ATP2B1

SNV

Missense_Mutation

c.703N>A

p.Asp235Asn

p.D235N

P20020

protein_coding

deleterious(0.05)

probably_damaging(0.996)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ATP2B1

SNV

Missense_Mutation

c.3007A>G

p.Ile1003Val

p.I1003V

P20020

protein_coding

tolerated(0.17)

benign(0.003)

TCGA-AN-A0FX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ATP2B1

SNV

Missense_Mutation

c.2563N>C

p.Phe855Leu

p.F855L

P20020

protein_coding

deleterious(0.02)

probably_damaging(0.979)

TCGA-C8-A12O-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ATP2B1

SNV

Missense_Mutation

novel

c.2222G>A

p.Arg741Lys

p.R741K

P20020

protein_coding

tolerated(0.15)

benign(0.033)

TCGA-C8-A274-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

ATP2B1

SNV

Missense_Mutation

novel

c.3278N>C

p.Ile1093Thr

p.I1093T

P20020

protein_coding

deleterious(0.03)

benign(0.079)

TCGA-C8-A8HQ-01

Breast

breast invasive 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
490	ATP2B1	DRUGGABLE GENOME, TRANSPORTER, ENZYME		Antihypertensives		25385345

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