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: SLC29A1

Gene summary for SLC29A1

Gene summary.

Gene information	Species	Human
	Gene symbol	SLC29A1
	Gene ID	2030
	Gene name	solute carrier family 29 member 1 (Augustine blood group)
	Gene Alias	ENT1
	Cytomap	6p21.1
	Gene Type	protein-coding
	GO ID	GO:0001504
	UniProtAcc	Q99808

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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
2030	SLC29A1	P48T-E	Human	Esophagus	ESCC	4.07e-07	1.15e-01	0.0959
2030	SLC29A1	P49T-E	Human	Esophagus	ESCC	4.40e-09	1.30e+00	0.1768
2030	SLC29A1	P52T-E	Human	Esophagus	ESCC	1.09e-23	6.30e-01	0.1555
2030	SLC29A1	P57T-E	Human	Esophagus	ESCC	3.04e-11	1.56e-01	0.0926
2030	SLC29A1	P61T-E	Human	Esophagus	ESCC	1.61e-06	1.45e-01	0.099
2030	SLC29A1	P65T-E	Human	Esophagus	ESCC	4.20e-11	3.33e-01	0.0978
2030	SLC29A1	P74T-E	Human	Esophagus	ESCC	2.93e-12	5.48e-01	0.1479
2030	SLC29A1	P75T-E	Human	Esophagus	ESCC	5.45e-05	1.90e-01	0.1125
2030	SLC29A1	P76T-E	Human	Esophagus	ESCC	1.27e-20	5.12e-01	0.1207
2030	SLC29A1	P79T-E	Human	Esophagus	ESCC	2.76e-39	8.11e-01	0.1154
2030	SLC29A1	P80T-E	Human	Esophagus	ESCC	1.58e-11	6.68e-01	0.155
2030	SLC29A1	P82T-E	Human	Esophagus	ESCC	1.82e-07	5.48e-01	0.1072
2030	SLC29A1	P83T-E	Human	Esophagus	ESCC	3.16e-24	1.26e+00	0.1738
2030	SLC29A1	P89T-E	Human	Esophagus	ESCC	1.03e-10	8.30e-01	0.1752
2030	SLC29A1	P91T-E	Human	Esophagus	ESCC	2.13e-09	1.13e+00	0.1828
2030	SLC29A1	P104T-E	Human	Esophagus	ESCC	8.14e-10	7.79e-01	0.0931
2030	SLC29A1	P107T-E	Human	Esophagus	ESCC	5.79e-37	1.12e+00	0.171
2030	SLC29A1	P128T-E	Human	Esophagus	ESCC	3.46e-17	5.66e-01	0.1241
2030	SLC29A1	P130T-E	Human	Esophagus	ESCC	2.27e-72	1.73e+00	0.1676
2030	SLC29A1	HCC1_Meng	Human	Liver	HCC	3.98e-24	2.94e-02	0.0246

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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
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
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:0048732	Colorectum	AD	gland development	149/3918	436/18723	6.07e-11	6.33e-09	149
GO:0009743	Colorectum	AD	response to carbohydrate	86/3918	253/18723	8.43e-07	2.90e-05	86
GO:0030879	Colorectum	AD	mammary gland development	53/3918	137/18723	1.46e-06	4.58e-05	53
GO:0034284	Colorectum	AD	response to monosaccharide	76/3918	225/18723	4.64e-06	1.23e-04	76
GO:0033500	Colorectum	AD	carbohydrate homeostasis	84/3918	259/18723	9.10e-06	2.15e-04	84
GO:0009746	Colorectum	AD	response to hexose	73/3918	219/18723	1.20e-05	2.65e-04	73
GO:0009749	Colorectum	AD	response to glucose	71/3918	212/18723	1.31e-05	2.85e-04	71
GO:0042593	Colorectum	AD	glucose homeostasis	83/3918	258/18723	1.44e-05	3.11e-04	83
GO:0001678	Colorectum	AD	cellular glucose homeostasis	60/3918	172/18723	1.49e-05	3.18e-04	60
GO:0015931	Colorectum	AD	nucleobase-containing compound transport	73/3918	222/18723	2.02e-05	4.10e-04	73
GO:0071322	Colorectum	AD	cellular response to carbohydrate stimulus	56/3918	163/18723	4.61e-05	7.97e-04	56
GO:0071333	Colorectum	AD	cellular response to glucose stimulus	52/3918	151/18723	7.88e-05	1.25e-03	52
GO:0071331	Colorectum	AD	cellular response to hexose stimulus	52/3918	153/18723	1.16e-04	1.71e-03	52
GO:0071326	Colorectum	AD	cellular response to monosaccharide stimulus	52/3918	154/18723	1.40e-04	1.98e-03	52
GO:0050878	Colorectum	AD	regulation of body fluid levels	108/3918	379/18723	2.54e-04	3.20e-03	108
GO:0070482	Colorectum	AD	response to oxygen levels	99/3918	347/18723	4.29e-04	4.82e-03	99
GO:0007589	Colorectum	AD	body fluid secretion	33/3918	93/18723	8.26e-04	8.13e-03	33
GO:0071453	Colorectum	AD	cellular response to oxygen levels	55/3918	177/18723	9.48e-04	8.96e-03	55
GO:0001666	Colorectum	AD	response to hypoxia	86/3918	307/18723	1.77e-03	1.46e-02	86
GO:0036293	Colorectum	AD	response to decreased oxygen levels	88/3918	322/18723	3.42e-03	2.49e-02	88

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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

SLC29A1

insertion

In_Frame_Ins

novel

c.1052_1053insGTTTCCAGCCGTGACTGTTGAGGTCAAGTCCAGCATCGCAGGCAGCAG

p.Phe351delinsLeuPheProAlaValThrValGluValLysSerSerIleAlaGlySerSer

p.F351delinsLFPAVTVEVKSSIAGSS

Q99808

protein_coding

TCGA-A2-A0CP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

SLC29A1

insertion

In_Frame_Ins

novel

c.683_684insTGCCTCCACCACCTGCAGAACCCTCTTGCCTTCAGC

p.Arg228_Leu229insAlaSerThrThrCysArgThrLeuLeuProSerAla

p.R228_L229insASTTCRTLLPSA

Q99808

protein_coding

TCGA-A8-A09D-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

SLC29A1

insertion

Frame_Shift_Ins

novel

c.126_127insTGGGAGTTTTTCCTTCTGCT

p.Leu43TrpfsTer21

p.L43Wfs*21

Q99808

protein_coding

TCGA-AN-A0FS-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SLC29A1

deletion

Frame_Shift_Del

c.134_173delTGTCCCAGAATGTGTCCTTGGTCACTGCTGAACTGAGCAA

p.Met45ArgfsTer27

p.M45Rfs*27

Q99808

protein_coding

TCGA-AO-A0J6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

SLC29A1

SNV

Missense_Mutation

c.214G>C

p.Glu72Gln

p.E72Q

Q99808

protein_coding

tolerated(0.31)

benign(0.009)

TCGA-Q1-A73O-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SLC29A1

SNV

Missense_Mutation

c.112T>C

p.Tyr38His

p.Y38H

Q99808

protein_coding

deleterious(0.02)

probably_damaging(0.999)

TCGA-AA-A00N-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

SLC29A1

SNV

Missense_Mutation

c.520N>C

p.Ala174Pro

p.A174P

Q99808

protein_coding

deleterious(0.01)

probably_damaging(0.98)

TCGA-CM-6162-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Chemotherapy

oxaliplatin

SLC29A1

SNV

Missense_Mutation

novel

c.641N>A

p.Ala214Asp

p.A214D

Q99808

protein_coding

deleterious(0)

benign(0.202)

TCGA-AJ-A3BH-01

Endometrium

uterine corpus endometrioid carcinoma

Female

Unknown

I/II

Unknown

SLC29A1

SNV

Missense_Mutation

novel

c.533N>A

p.Ser178Asn

p.S178N

Q99808

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AP-A051-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

SLC29A1

SNV

Missense_Mutation

c.793N>A

p.Glu265Lys

p.E265K

Q99808

protein_coding

tolerated(0.54)

benign(0.007)

TCGA-AP-A0LM-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

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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
2030	SLC29A1	TRANSPORTER, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUGGABLE GENOME		gemcitabine	GEMCITABINE	25162786,20665488,22705007,24475233,24361227
2030	SLC29A1	TRANSPORTER, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUGGABLE GENOME		paclitaxel	PACLITAXEL	24361227
2030	SLC29A1	TRANSPORTER, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUGGABLE GENOME	inhibitor	178101311	DRAFLAZINE
2030	SLC29A1	TRANSPORTER, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUGGABLE GENOME	inhibitor	178101445
2030	SLC29A1	TRANSPORTER, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUGGABLE GENOME		ETHANOL	ALCOHOL	15258586
2030	SLC29A1	TRANSPORTER, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUGGABLE GENOME	inhibitor	178101238
2030	SLC29A1	TRANSPORTER, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUGGABLE GENOME		LIDOFLAZINE	LIDOFLAZINE
2030	SLC29A1	TRANSPORTER, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUGGABLE GENOME		TECADENOSON	TECADENOSON	23388705
2030	SLC29A1	TRANSPORTER, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUGGABLE GENOME		ribavirin	RIBAVIRIN	20812847
2030	SLC29A1	TRANSPORTER, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUGGABLE GENOME	inhibitor	CHEMBL932	DIPYRIDAMOLE

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