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: SLC5A3

Gene summary for SLC5A3

Gene summary.

Gene information	Species	Human
	Gene symbol	SLC5A3
	Gene ID	6526
	Gene name	solute carrier family 5 member 3
	Gene Alias	BCW2
	Cytomap	21q22.11
	Gene Type	protein-coding
	GO ID	GO:0003008
	UniProtAcc	NA

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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
6526	SLC5A3	LZE4T	Human	Esophagus	ESCC	8.64e-08	4.29e-01	0.0811
6526	SLC5A3	LZE7T	Human	Esophagus	ESCC	1.77e-10	9.10e-01	0.0667
6526	SLC5A3	LZE8T	Human	Esophagus	ESCC	1.55e-05	1.66e-01	0.067
6526	SLC5A3	LZE20T	Human	Esophagus	ESCC	3.99e-03	2.37e-01	0.0662
6526	SLC5A3	LZE22T	Human	Esophagus	ESCC	2.92e-04	2.44e-01	0.068
6526	SLC5A3	LZE24T	Human	Esophagus	ESCC	2.47e-06	-2.18e-02	0.0596
6526	SLC5A3	LZE6T	Human	Esophagus	ESCC	1.05e-07	3.45e-01	0.0845
6526	SLC5A3	P1T-E	Human	Esophagus	ESCC	4.06e-03	1.59e-01	0.0875
6526	SLC5A3	P2T-E	Human	Esophagus	ESCC	4.57e-07	9.35e-02	0.1177
6526	SLC5A3	P4T-E	Human	Esophagus	ESCC	6.43e-08	3.63e-01	0.1323
6526	SLC5A3	P5T-E	Human	Esophagus	ESCC	6.06e-11	2.43e-01	0.1327
6526	SLC5A3	P8T-E	Human	Esophagus	ESCC	1.88e-14	3.56e-02	0.0889
6526	SLC5A3	P9T-E	Human	Esophagus	ESCC	1.68e-09	4.35e-02	0.1131
6526	SLC5A3	P10T-E	Human	Esophagus	ESCC	5.64e-14	3.18e-01	0.116
6526	SLC5A3	P12T-E	Human	Esophagus	ESCC	9.20e-22	5.00e-01	0.1122
6526	SLC5A3	P15T-E	Human	Esophagus	ESCC	7.11e-09	8.09e-02	0.1149
6526	SLC5A3	P16T-E	Human	Esophagus	ESCC	1.64e-08	8.39e-02	0.1153
6526	SLC5A3	P20T-E	Human	Esophagus	ESCC	2.03e-05	3.09e-02	0.1124
6526	SLC5A3	P21T-E	Human	Esophagus	ESCC	1.24e-14	1.67e-01	0.1617
6526	SLC5A3	P22T-E	Human	Esophagus	ESCC	2.18e-17	2.70e-01	0.1236

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
Prostate		BPH: Benign Prostatic Hyperplasia
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:1903829111	Esophagus	ESCC	positive regulation of cellular protein localization	199/8552	276/18723	2.99e-19	3.45e-17	199
GO:190547519	Esophagus	ESCC	regulation of protein localization to membrane	117/8552	175/18723	1.14e-08	2.26e-07	117
GO:190547719	Esophagus	ESCC	positive regulation of protein localization to membrane	73/8552	106/18723	1.13e-06	1.40e-05	73
GO:200037718	Esophagus	ESCC	regulation of reactive oxygen species metabolic process	100/8552	157/18723	3.87e-06	4.17e-05	100
GO:00060668	Esophagus	ESCC	alcohol metabolic process	202/8552	353/18723	7.32e-06	7.26e-05	202
GO:00442626	Esophagus	ESCC	cellular carbohydrate metabolic process	160/8552	283/18723	1.43e-04	9.66e-04	160
GO:007259318	Esophagus	ESCC	reactive oxygen species metabolic process	137/8552	239/18723	1.82e-04	1.16e-03	137
GO:200037918	Esophagus	ESCC	positive regulation of reactive oxygen species metabolic process	45/8552	76/18723	1.21e-02	4.04e-02	45
GO:190382922	Liver	HCC	positive regulation of cellular protein localization	199/7958	276/18723	1.15e-23	2.62e-21	199
GO:000606621	Liver	HCC	alcohol metabolic process	208/7958	353/18723	2.80e-10	9.50e-09	208
GO:190547511	Liver	HCC	regulation of protein localization to membrane	113/7958	175/18723	2.90e-09	7.78e-08	113
GO:190547711	Liver	HCC	positive regulation of protein localization to membrane	68/7958	106/18723	5.50e-06	6.82e-05	68
GO:200037722	Liver	HCC	regulation of reactive oxygen species metabolic process	92/7958	157/18723	3.34e-05	3.35e-04	92
GO:004426221	Liver	HCC	cellular carbohydrate metabolic process	153/7958	283/18723	5.27e-05	5.00e-04	153
GO:200037912	Liver	HCC	positive regulation of reactive oxygen species metabolic process	47/7958	76/18723	5.19e-04	3.38e-03	47
GO:007259312	Liver	HCC	reactive oxygen species metabolic process	124/7958	239/18723	2.05e-03	1.04e-02	124
GO:015010411	Liver	HCC	transport across blood-brain barrier	50/7958	87/18723	3.42e-03	1.55e-02	50
GO:001023211	Liver	HCC	vascular transport	50/7958	88/18723	4.69e-03	2.02e-02	50
GO:0008643	Liver	HCC	carbohydrate transport	80/7958	152/18723	7.34e-03	2.92e-02	80
GO:190382920	Oral cavity	OSCC	positive regulation of cellular protein localization	179/7305	276/18723	2.20e-18	2.41e-16	179

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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

SLC5A3

SNV

Missense_Mutation

novel

c.163N>G

p.Leu55Val

p.L55V

P53794

protein_coding

deleterious(0.01)

probably_damaging(0.999)

TCGA-AR-A2LE-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

SLC5A3

SNV

Missense_Mutation

c.145G>T

p.Val49Leu

p.V49L

P53794

protein_coding

tolerated(0.12)

benign(0.003)

TCGA-BH-A0H5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

SLC5A3

SNV

Missense_Mutation

novel

c.34A>G

p.Ile12Val

p.I12V

P53794

protein_coding

tolerated(1)

benign(0.003)

TCGA-D8-A1JJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine

SLC5A3

SNV

Missense_Mutation

c.880C>T

p.His294Tyr

p.H294Y

P53794

protein_coding

deleterious(0)

possibly_damaging(0.855)

TCGA-EW-A1OV-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

epirubicin

SLC5A3

SNV

Missense_Mutation

novel

c.1702N>A

p.Gln568Lys

p.Q568K

P53794

protein_coding

tolerated(0.72)

benign(0.135)

TCGA-GM-A3XL-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

fluorouracil

SLC5A3

insertion

Nonsense_Mutation

novel

c.1470_1471insGGATGACTTGGA

p.Ala490_Tyr491insGlyTerLeuGly

p.A490_Y491insG*LG

P53794

protein_coding

TCGA-AN-A04A-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

SLC5A3

insertion

Frame_Shift_Ins

novel

c.209_210insTTTTTTTTCTTTTT

p.Ser71PhefsTer66

p.S71Ffs*66

P53794

protein_coding

TCGA-AO-A0JB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

SLC5A3

insertion

Nonsense_Mutation

novel

c.211_212insAAAGAATGTCTTGTTGCGCCGTGTTTGCTAGA

p.Ser71Ter

p.S71*

P53794

protein_coding

TCGA-AO-A0JB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

SLC5A3

insertion

Nonsense_Mutation

novel

c.412_413insTATGACAACTATATCCATTTACTGGAGTTTAAGAAGCTTTATAAC

p.Lys138delinsIleTerGlnLeuTyrProPheThrGlyValTerGluAlaLeuTerGln

p.K138delinsI*QLYPFTGV*EAL*Q

P53794

protein_coding

TCGA-AO-A0JD-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

SLC5A3

deletion

Frame_Shift_Del

c.72delN

p.Phe26LeufsTer11

p.F26Lfs*11

P53794

protein_coding

TCGA-BH-A0HA-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
6526	SLC5A3	EXTERNAL SIDE OF PLASMA MEMBRANE, DRUGGABLE GENOME, TRANSPORTER	inhibitor	178101467	PHLORIZIN

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