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: SLCO3A1

Gene summary for SLCO3A1

Gene summary.

Gene information	Species	Human
	Gene symbol	SLCO3A1
	Gene ID	28232
	Gene name	solute carrier organic anion transporter family member 3A1
	Gene Alias	OATP-D
	Cytomap	15q26.1
	Gene Type	protein-coding
	GO ID	GO:0001932
	UniProtAcc	Q9UIG8

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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
28232	SLCO3A1	CA_HPV_2	Human	Cervix	CC	5.30e-03	2.93e-01	0.0391
28232	SLCO3A1	CCI_1	Human	Cervix	CC	8.20e-03	1.84e+00	0.528
28232	SLCO3A1	CCI_2	Human	Cervix	CC	3.54e-07	1.53e+00	0.5249
28232	SLCO3A1	CCI_3	Human	Cervix	CC	1.86e-07	1.14e+00	0.516
28232	SLCO3A1	H2	Human	Cervix	HSIL_HPV	4.34e-02	-2.04e-01	0.0632
28232	SLCO3A1	HTA11_3410_2000001011	Human	Colorectum	AD	3.21e-13	-4.76e-01	0.0155
28232	SLCO3A1	HTA11_2487_2000001011	Human	Colorectum	SER	2.13e-09	-6.21e-01	-0.1808
28232	SLCO3A1	HTA11_1938_2000001011	Human	Colorectum	AD	1.18e-07	-6.09e-01	-0.0811
28232	SLCO3A1	HTA11_78_2000001011	Human	Colorectum	AD	4.22e-13	-6.73e-01	-0.1088
28232	SLCO3A1	HTA11_3361_2000001011	Human	Colorectum	AD	1.12e-04	-5.62e-01	-0.1207
28232	SLCO3A1	HTA11_83_2000001011	Human	Colorectum	SER	1.36e-06	-6.70e-01	-0.1526
28232	SLCO3A1	HTA11_866_2000001011	Human	Colorectum	AD	3.94e-03	-3.30e-01	-0.1001
28232	SLCO3A1	HTA11_1391_2000001011	Human	Colorectum	AD	4.31e-06	-4.86e-01	-0.059
28232	SLCO3A1	HTA11_6818_2000001021	Human	Colorectum	AD	1.22e-02	-3.90e-01	0.0588
28232	SLCO3A1	HTA11_99999971662_82457	Human	Colorectum	MSS	4.44e-19	-5.44e-01	0.3859
28232	SLCO3A1	HTA11_99999974143_84620	Human	Colorectum	MSS	1.15e-08	-4.54e-01	0.3005
28232	SLCO3A1	A015-C-203	Human	Colorectum	FAP	1.51e-18	1.58e-01	-0.1294
28232	SLCO3A1	A015-C-204	Human	Colorectum	FAP	4.70e-06	-3.61e-01	-0.0228
28232	SLCO3A1	A002-C-201	Human	Colorectum	FAP	3.81e-09	-2.50e-01	0.0324
28232	SLCO3A1	A002-C-203	Human	Colorectum	FAP	3.18e-13	-4.28e-01	0.2786

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
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:00510904	Cervix	CC	regulation of DNA-binding transcription factor activity	87/2311	440/18723	4.85e-06	1.22e-04	87
GO:00510915	Cervix	CC	positive regulation of DNA-binding transcription factor activity	51/2311	260/18723	5.05e-04	4.92e-03	51
GO:00510923	Cervix	CC	positive regulation of NF-kappaB transcription factor activity	32/2311	152/18723	1.62e-03	1.25e-02	32
GO:005109211	Cervix	HSIL_HPV	positive regulation of NF-kappaB transcription factor activity	20/737	152/18723	2.25e-06	9.41e-05	20
GO:005109012	Cervix	HSIL_HPV	regulation of DNA-binding transcription factor activity	35/737	440/18723	6.77e-05	1.58e-03	35
GO:005109112	Cervix	HSIL_HPV	positive regulation of DNA-binding transcription factor activity	24/737	260/18723	1.01e-04	2.16e-03	24
GO:0015732	Colorectum	AD	prostaglandin transport	10/3918	18/18723	1.31e-03	1.15e-02	10
GO:0010876	Colorectum	AD	lipid localization	120/3918	448/18723	1.59e-03	1.33e-02	120
GO:0006869	Colorectum	AD	lipid transport	108/3918	398/18723	1.67e-03	1.39e-02	108
GO:0051091	Colorectum	AD	positive regulation of DNA-binding transcription factor activity	73/3918	260/18723	3.52e-03	2.54e-02	73
GO:00510911	Colorectum	SER	positive regulation of DNA-binding transcription factor activity	56/2897	260/18723	5.55e-03	4.09e-02	56
GO:00510912	Colorectum	MSS	positive regulation of DNA-binding transcription factor activity	69/3467	260/18723	8.44e-04	8.71e-03	69
GO:0150104	Colorectum	MSS	transport across blood-brain barrier	28/3467	87/18723	1.54e-03	1.41e-02	28
GO:0010232	Colorectum	MSS	vascular transport	28/3467	88/18723	1.87e-03	1.64e-02	28
GO:0051090	Colorectum	MSS	regulation of DNA-binding transcription factor activity	106/3467	440/18723	1.88e-03	1.65e-02	106
GO:00108761	Colorectum	MSS	lipid localization	104/3467	448/18723	6.76e-03	4.38e-02	104
GO:01501041	Colorectum	FAP	transport across blood-brain barrier	25/2622	87/18723	2.63e-04	3.59e-03	25
GO:00068691	Colorectum	FAP	lipid transport	81/2622	398/18723	2.84e-04	3.76e-03	81
GO:00157321	Colorectum	FAP	prostaglandin transport	9/2622	18/18723	3.00e-04	3.90e-03	9
GO:00102321	Colorectum	FAP	vascular transport	25/2622	88/18723	3.19e-04	4.12e-03	25

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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

SLCO3A1

SNV

Missense_Mutation

rs775241468

c.1184C>T

p.Ala395Val

p.A395V

Q9UIG8

protein_coding

deleterious(0)

benign(0.33)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SLCO3A1

SNV

Missense_Mutation

c.1408N>T

p.Pro470Ser

p.P470S

Q9UIG8

protein_coding

tolerated(0.73)

benign(0.006)

TCGA-AN-A0FZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

SLCO3A1

SNV

Missense_Mutation

c.1073N>T

p.Ala358Val

p.A358V

Q9UIG8

protein_coding

deleterious(0.02)

possibly_damaging(0.81)

TCGA-AO-A0J9-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

SLCO3A1

SNV

Missense_Mutation

rs767466440

c.1558N>A

p.Ala520Thr

p.A520T

Q9UIG8

protein_coding

tolerated(0.1)

benign(0.106)

TCGA-E2-A1LE-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

herceptin

SLCO3A1

SNV

Missense_Mutation

novel

c.949N>C

p.Gly317Arg

p.G317R

Q9UIG8

protein_coding

tolerated(0.11)

possibly_damaging(0.764)

TCGA-S3-AA17-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

anastrozole

SLCO3A1

SNV

Missense_Mutation

novel

c.950N>A

p.Gly317Glu

p.G317E

Q9UIG8

protein_coding

tolerated(0.25)

benign(0.098)

TCGA-S3-AA17-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

anastrozole

SLCO3A1

insertion

Nonsense_Mutation

novel

c.282_283insGGCCTCATGCATACTTAGTCTGTCTTCTCAAAATTGTGTT

p.Phe95GlyfsTer6

p.F95Gfs*6

Q9UIG8

protein_coding

TCGA-AN-A049-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SLCO3A1

SNV

Missense_Mutation

novel

c.451N>A

p.Ala151Thr

p.A151T

Q9UIG8

protein_coding

tolerated(0.42)

benign(0.046)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SLCO3A1

SNV

Missense_Mutation

novel

c.1909G>A

p.Ala637Thr

p.A637T

Q9UIG8

protein_coding

tolerated(0.08)

benign(0.339)

TCGA-EA-A410-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SLCO3A1

SNV

Missense_Mutation

rs747216199

c.939N>T

p.Lys313Asn

p.K313N

Q9UIG8

protein_coding

tolerated(0.19)

benign(0.026)

TCGA-A6-3809-01

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
28232	SLCO3A1	TRANSPORTER, DRUGGABLE GENOME		178101458
28232	SLCO3A1	TRANSPORTER, DRUGGABLE GENOME		135651569

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