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: SLC20A1

Gene summary for SLC20A1

Gene summary.

Gene information	Species	Human
	Gene symbol	SLC20A1
	Gene ID	6574
	Gene name	solute carrier family 20 member 1
	Gene Alias	GLVR1
	Cytomap	2q14.1
	Gene Type	protein-coding
	GO ID	GO:0006793
	UniProtAcc	A7LNJ1

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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
6574	SLC20A1	HTA11_3410_2000001011	Human	Colorectum	AD	6.48e-04	-2.24e-01	0.0155
6574	SLC20A1	HTA11_866_3004761011	Human	Colorectum	AD	7.37e-03	-2.22e-01	0.096
6574	SLC20A1	A015-C-203	Human	Colorectum	FAP	1.41e-02	-9.17e-03	-0.1294
6574	SLC20A1	A002-C-205	Human	Colorectum	FAP	1.33e-02	-1.04e-01	-0.1236
6574	SLC20A1	A002-C-114	Human	Colorectum	FAP	1.73e-02	-1.79e-01	-0.1561
6574	SLC20A1	F072B	Human	Colorectum	FAP	1.56e-02	-2.03e-01	0.257
6574	SLC20A1	LZE4T	Human	Esophagus	ESCC	2.02e-02	1.10e-01	0.0811
6574	SLC20A1	LZE5T	Human	Esophagus	ESCC	4.16e-05	8.91e-02	0.0514
6574	SLC20A1	LZE7T	Human	Esophagus	ESCC	2.44e-03	3.94e-01	0.0667
6574	SLC20A1	LZE8T	Human	Esophagus	ESCC	6.50e-12	-3.84e-01	0.067
6574	SLC20A1	LZE20T	Human	Esophagus	ESCC	3.60e-05	-8.03e-02	0.0662
6574	SLC20A1	LZE22T	Human	Esophagus	ESCC	1.85e-02	-4.42e-02	0.068
6574	SLC20A1	LZE24T	Human	Esophagus	ESCC	6.32e-08	8.28e-02	0.0596
6574	SLC20A1	LZE21T	Human	Esophagus	ESCC	1.78e-03	1.53e-01	0.0655
6574	SLC20A1	P1T-E	Human	Esophagus	ESCC	2.77e-02	4.37e-01	0.0875
6574	SLC20A1	P2T-E	Human	Esophagus	ESCC	1.05e-31	-3.33e-01	0.1177
6574	SLC20A1	P4T-E	Human	Esophagus	ESCC	7.18e-15	5.71e-01	0.1323
6574	SLC20A1	P5T-E	Human	Esophagus	ESCC	9.57e-09	7.69e-02	0.1327
6574	SLC20A1	P8T-E	Human	Esophagus	ESCC	1.71e-06	-1.33e-01	0.0889
6574	SLC20A1	P9T-E	Human	Esophagus	ESCC	1.20e-11	4.09e-01	0.1131

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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
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:0043123	Colorectum	AD	positive regulation of I-kappaB kinase/NF-kappaB signaling	60/3918	186/18723	1.91e-04	2.56e-03	60
GO:0043122	Colorectum	AD	regulation of I-kappaB kinase/NF-kappaB signaling	76/3918	249/18723	2.17e-04	2.85e-03	76
GO:0007249	Colorectum	AD	I-kappaB kinase/NF-kappaB signaling	82/3918	281/18723	6.09e-04	6.40e-03	82
GO:0015698	Colorectum	AD	inorganic anion transport	52/3918	180/18723	6.83e-03	4.22e-02	52
GO:0035725	Colorectum	FAP	sodium ion transmembrane transport	44/2622	178/18723	9.31e-05	1.60e-03	44
GO:00431222	Colorectum	FAP	regulation of I-kappaB kinase/NF-kappaB signaling	56/2622	249/18723	1.82e-04	2.69e-03	56
GO:0006814	Colorectum	FAP	sodium ion transport	54/2622	245/18723	3.98e-04	4.85e-03	54
GO:00431232	Colorectum	FAP	positive regulation of I-kappaB kinase/NF-kappaB signaling	42/2622	186/18723	1.01e-03	9.89e-03	42
GO:00072492	Colorectum	FAP	I-kappaB kinase/NF-kappaB signaling	58/2622	281/18723	1.37e-03	1.24e-02	58
GO:00156981	Colorectum	FAP	inorganic anion transport	38/2622	180/18723	5.73e-03	3.67e-02	38
GO:004312318	Esophagus	ESCC	positive regulation of I-kappaB kinase/NF-kappaB signaling	132/8552	186/18723	2.07e-12	8.58e-11	132
GO:0043122110	Esophagus	ESCC	regulation of I-kappaB kinase/NF-kappaB signaling	167/8552	249/18723	6.11e-12	2.32e-10	167
GO:000724919	Esophagus	ESCC	I-kappaB kinase/NF-kappaB signaling	183/8552	281/18723	3.02e-11	1.01e-09	183
GO:00072494	Liver	Cirrhotic	I-kappaB kinase/NF-kappaB signaling	108/4634	281/18723	2.21e-07	5.64e-06	108
GO:00431225	Liver	Cirrhotic	regulation of I-kappaB kinase/NF-kappaB signaling	95/4634	249/18723	1.68e-06	3.22e-05	95
GO:00431234	Liver	Cirrhotic	positive regulation of I-kappaB kinase/NF-kappaB signaling	71/4634	186/18723	3.20e-05	3.97e-04	71
GO:000724912	Liver	HCC	I-kappaB kinase/NF-kappaB signaling	156/7958	281/18723	6.66e-06	8.00e-05	156
GO:004312312	Liver	HCC	positive regulation of I-kappaB kinase/NF-kappaB signaling	108/7958	186/18723	1.28e-05	1.43e-04	108
GO:004312212	Liver	HCC	regulation of I-kappaB kinase/NF-kappaB signaling	138/7958	249/18723	2.47e-05	2.58e-04	138
GO:00072495	Lung	IAC	I-kappaB kinase/NF-kappaB signaling	56/2061	281/18723	7.39e-06	2.62e-04	56

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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

SLC20A1

SNV

Missense_Mutation

rs142437239

c.1603N>A

p.Val535Ile

p.V535I

Q8WUM9

protein_coding

deleterious(0)

probably_damaging(0.984)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SLC20A1

SNV

Missense_Mutation

c.1333A>C

p.Met445Leu

p.M445L

Q8WUM9

protein_coding

tolerated(0.32)

benign(0.021)

TCGA-AO-A03P-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

letrozole

SLC20A1

SNV

Missense_Mutation

c.340G>T

p.Ala114Ser

p.A114S

Q8WUM9

protein_coding

tolerated(0.12)

benign(0.192)

TCGA-D8-A140-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin+cyclophosphamid

SLC20A1

insertion

Frame_Shift_Ins

novel

c.1837_1838insGTGCAGTGCAGTTGCCTAATGGGAACCTTGTC

p.Ala613GlyfsTer82

p.A613Gfs*82

Q8WUM9

protein_coding

TCGA-AN-A0FN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SLC20A1

SNV

Missense_Mutation

novel

c.1676C>T

p.Ala559Val

p.A559V

Q8WUM9

protein_coding

tolerated(0.25)

benign(0.02)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SLC20A1

SNV

Missense_Mutation

c.779N>A

p.Arg260Gln

p.R260Q

Q8WUM9

protein_coding

tolerated(0.58)

benign(0.066)

TCGA-DR-A0ZM-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unspecific

Cisplatin

SLC20A1

insertion

Nonsense_Mutation

novel

c.171_172insGTTGTTTAGT

p.Thr58ValfsTer3

p.T58Vfs*3

Q8WUM9

protein_coding

TCGA-DS-A1OD-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SLC20A1

SNV

Missense_Mutation

rs751466959

c.1301G>A

p.Arg434His

p.R434H

Q8WUM9

protein_coding

tolerated(0.17)

possibly_damaging(0.75)

TCGA-AA-3864-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

SLC20A1

SNV

Missense_Mutation

c.1409N>T

p.Ala470Val

p.A470V

Q8WUM9

protein_coding

deleterious(0.02)

probably_damaging(0.98)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

SLC20A1

SNV

Missense_Mutation

c.280A>G

p.Met94Val

p.M94V

Q8WUM9

protein_coding

tolerated(0.24)

benign(0.003)

TCGA-AM-5821-01

Colorectum

colon adenocarcinoma

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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