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: SLC16A1

Gene summary for SLC16A1

Gene summary.

Gene information	Species	Human
	Gene symbol	SLC16A1
	Gene ID	6566
	Gene name	solute carrier family 16 member 1
	Gene Alias	HHF7
	Cytomap	1p13.2
	Gene Type	protein-coding
	GO ID	GO:0000226
	UniProtAcc	A0A024R0H1

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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
6566	SLC16A1	HTA11_1938_2000001011	Human	Colorectum	AD	4.43e-03	4.08e-01	-0.0811
6566	SLC16A1	HTA11_83_2000001011	Human	Colorectum	SER	1.38e-05	5.91e-01	-0.1526
6566	SLC16A1	HTA11_99999970781_79442	Human	Colorectum	MSS	3.00e-03	3.07e-01	0.294
6566	SLC16A1	HTA11_99999971662_82457	Human	Colorectum	MSS	4.32e-10	5.18e-01	0.3859
6566	SLC16A1	A015-C-203	Human	Colorectum	FAP	4.90e-03	-1.63e-01	-0.1294
6566	SLC16A1	A002-C-205	Human	Colorectum	FAP	5.97e-05	-1.90e-01	-0.1236
6566	SLC16A1	A015-C-005	Human	Colorectum	FAP	5.99e-04	-2.04e-01	-0.0336
6566	SLC16A1	A002-C-114	Human	Colorectum	FAP	2.07e-04	-1.97e-01	-0.1561
6566	SLC16A1	A015-C-104	Human	Colorectum	FAP	1.01e-03	-1.85e-01	-0.1899
6566	SLC16A1	A002-C-016	Human	Colorectum	FAP	3.90e-04	-1.43e-01	0.0521
6566	SLC16A1	A015-C-002	Human	Colorectum	FAP	1.17e-03	-2.16e-01	-0.0763
6566	SLC16A1	A002-C-116	Human	Colorectum	FAP	3.57e-03	-1.48e-01	-0.0452
6566	SLC16A1	A014-C-008	Human	Colorectum	FAP	2.33e-04	-2.16e-01	-0.191
6566	SLC16A1	A018-E-020	Human	Colorectum	FAP	5.75e-05	-2.00e-01	-0.2034
6566	SLC16A1	LZE4T	Human	Esophagus	ESCC	3.98e-10	2.00e-01	0.0811
6566	SLC16A1	LZE5T	Human	Esophagus	ESCC	2.86e-02	-4.75e-01	0.0514
6566	SLC16A1	LZE7T	Human	Esophagus	ESCC	7.73e-11	-2.85e-01	0.0667
6566	SLC16A1	LZE8T	Human	Esophagus	ESCC	3.64e-08	-5.70e-01	0.067
6566	SLC16A1	LZE21D1	Human	Esophagus	HGIN	9.97e-03	-5.12e-01	0.0632
6566	SLC16A1	LZE22D1	Human	Esophagus	HGIN	3.13e-04	-6.05e-01	0.0595

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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
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:0033500	Colorectum	AD	carbohydrate homeostasis	84/3918	259/18723	9.10e-06	2.15e-04	84
GO:0031667	Colorectum	AD	response to nutrient levels	138/3918	474/18723	1.22e-05	2.68e-04	138
GO:0042593	Colorectum	AD	glucose homeostasis	83/3918	258/18723	1.44e-05	3.11e-04	83
GO:0050708	Colorectum	AD	regulation of protein secretion	83/3918	268/18723	6.59e-05	1.07e-03	83
GO:0009306	Colorectum	AD	protein secretion	105/3918	359/18723	1.05e-04	1.57e-03	105
GO:0035592	Colorectum	AD	establishment of protein localization to extracellular region	105/3918	360/18723	1.18e-04	1.73e-03	105
GO:0071692	Colorectum	AD	protein localization to extracellular region	106/3918	368/18723	1.86e-04	2.49e-03	106
GO:0050796	Colorectum	AD	regulation of insulin secretion	54/3918	165/18723	2.60e-04	3.25e-03	54
GO:0030073	Colorectum	AD	insulin secretion	61/3918	195/18723	4.28e-04	4.81e-03	61
GO:0015833	Colorectum	AD	peptide transport	77/3918	264/18723	8.90e-04	8.60e-03	77
GO:0090087	Colorectum	AD	regulation of peptide transport	60/3918	202/18723	1.94e-03	1.58e-02	60
GO:0030072	Colorectum	AD	peptide hormone secretion	68/3918	236/18723	2.39e-03	1.85e-02	68
GO:0002791	Colorectum	AD	regulation of peptide secretion	59/3918	200/18723	2.50e-03	1.92e-02	59
GO:0090276	Colorectum	AD	regulation of peptide hormone secretion	58/3918	196/18723	2.51e-03	1.92e-02	58
GO:0002790	Colorectum	AD	peptide secretion	69/3918	242/18723	2.97e-03	2.22e-02	69
GO:0042886	Colorectum	AD	amide transport	83/3918	301/18723	3.37e-03	2.46e-02	83
GO:00316671	Colorectum	SER	response to nutrient levels	106/2897	474/18723	3.94e-05	1.00e-03	106
GO:00507081	Colorectum	SER	regulation of protein secretion	63/2897	268/18723	3.42e-04	5.39e-03	63
GO:00093061	Colorectum	SER	protein secretion	79/2897	359/18723	5.99e-04	8.19e-03	79
GO:00355921	Colorectum	SER	establishment of protein localization to extracellular region	79/2897	360/18723	6.54e-04	8.77e-03	79

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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

SLC16A1

SNV

Missense_Mutation

rs151166713

c.1285G>A

p.Val429Ile

p.V429I

P53985

protein_coding

tolerated(1)

benign(0.012)

TCGA-A2-A25E-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

SLC16A1

SNV

Missense_Mutation

novel

c.1007C>T

p.Ser336Phe

p.S336F

P53985

protein_coding

deleterious(0)

probably_damaging(0.981)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SLC16A1

SNV

Missense_Mutation

c.402G>T

p.Met134Ile

p.M134I

P53985

protein_coding

tolerated(0.56)

benign(0.013)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SLC16A1

SNV

Missense_Mutation

rs759149434

c.256C>T

p.Arg86Cys

p.R86C

P53985

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SLC16A1

SNV

Missense_Mutation

novel

c.992N>G

p.Tyr331Cys

p.Y331C

P53985

protein_coding

deleterious(0.01)

probably_damaging(0.999)

TCGA-D8-A13Z-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine

SLC16A1

SNV

Missense_Mutation

c.867N>C

p.Lys289Asn

p.K289N

P53985

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-D8-A27G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SLC16A1

SNV

Missense_Mutation

rs746931470

c.1250N>A

p.Gly417Glu

p.G417E

P53985

protein_coding

deleterious(0.02)

possibly_damaging(0.597)

TCGA-E2-A15K-06

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

SLC16A1

SNV

Missense_Mutation

c.81C>G

p.Phe27Leu

p.F27L

P53985

protein_coding

deleterious(0.01)

probably_damaging(0.995)

TCGA-E2-A1IH-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

aromasin

SLC16A1

insertion

Frame_Shift_Ins

rs606231309

c.41dupC

p.Asp15ArgfsTer34

p.D15Rfs*34

P53985

protein_coding

TCGA-AN-A0FV-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SLC16A1

SNV

Missense_Mutation

novel

c.1499N>G

p.Val500Gly

p.V500G

P53985

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.637)

TCGA-EA-A3HS-01

Cervix

cervical & endocervical cancer

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
6566	SLC16A1	TRANSPORTER, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUGGABLE GENOME		BUTYRATE		11882670
6566	SLC16A1	TRANSPORTER, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUGGABLE GENOME		SODIUM BUTYRATE		11882670
6566	SLC16A1	TRANSPORTER, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUGGABLE GENOME	inhibitor	404859052
6566	SLC16A1	TRANSPORTER, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUGGABLE GENOME	inhibitor	252827471
6566	SLC16A1	TRANSPORTER, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUGGABLE GENOME		PMA		14525727
6566	SLC16A1	TRANSPORTER, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUGGABLE GENOME	inhibitor	384403683

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