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: SLCO2B1

Gene summary for SLCO2B1

Gene summary.

Gene information	Species	Human
	Gene symbol	SLCO2B1
	Gene ID	11309
	Gene name	solute carrier organic anion transporter family member 2B1
	Gene Alias	OATP-B
	Cytomap	11q13.4
	Gene Type	protein-coding
	GO ID	GO:0003008
	UniProtAcc	O94956

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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
11309	SLCO2B1	NAFLD1	Human	Liver	NAFLD	6.48e-12	1.02e+00	-0.04
11309	SLCO2B1	HCC1_Meng	Human	Liver	HCC	2.40e-48	8.74e-02	0.0246
11309	SLCO2B1	HCC2_Meng	Human	Liver	HCC	4.17e-02	-1.03e-01	0.0107
11309	SLCO2B1	cirrhotic1	Human	Liver	Cirrhotic	3.58e-02	-1.26e-01	0.0202
11309	SLCO2B1	HCC2	Human	Liver	HCC	4.51e-08	1.08e+00	0.5341
11309	SLCO2B1	S028	Human	Liver	HCC	1.69e-05	5.47e-01	0.2503
11309	SLCO2B1	S029	Human	Liver	HCC	1.46e-10	6.91e-01	0.2581

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Liver		HCC: Hepatocellular carcinoma
Liver		NAFLD: Non-alcoholic fatty liver disease

∗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:00194396	Liver	NAFLD	aromatic compound catabolic process	102/1882	467/18723	2.29e-14	1.91e-11	102
GO:19013616	Liver	NAFLD	organic cyclic compound catabolic process	105/1882	495/18723	7.04e-14	5.15e-11	105
GO:00442707	Liver	NAFLD	cellular nitrogen compound catabolic process	93/1882	451/18723	1.04e-11	4.34e-09	93
GO:00467006	Liver	NAFLD	heterocycle catabolic process	92/1882	445/18723	1.16e-11	4.52e-09	92
GO:00108765	Liver	NAFLD	lipid localization	79/1882	448/18723	4.75e-07	2.92e-05	79
GO:00068694	Liver	NAFLD	lipid transport	71/1882	398/18723	1.16e-06	5.59e-05	71
GO:0015850	Liver	NAFLD	organic hydroxy compound transport	50/1882	284/18723	6.01e-05	1.32e-03	50
GO:00030182	Liver	NAFLD	vascular process in circulatory system	46/1882	263/18723	1.36e-04	2.58e-03	46
GO:0015721	Liver	NAFLD	bile acid and bile salt transport	10/1882	30/18723	4.67e-04	6.74e-03	10
GO:01501043	Liver	NAFLD	transport across blood-brain barrier	17/1882	87/18723	5.46e-03	4.20e-02	17
GO:00102322	Liver	NAFLD	vascular transport	17/1882	88/18723	6.15e-03	4.61e-02	17
GO:190136111	Liver	Cirrhotic	organic cyclic compound catabolic process	213/4634	495/18723	1.58e-19	3.67e-17	213
GO:001943911	Liver	Cirrhotic	aromatic compound catabolic process	202/4634	467/18723	6.93e-19	1.28e-16	202
GO:004427011	Liver	Cirrhotic	cellular nitrogen compound catabolic process	195/4634	451/18723	2.99e-18	4.94e-16	195
GO:004670011	Liver	Cirrhotic	heterocycle catabolic process	192/4634	445/18723	7.17e-18	1.12e-15	192
GO:001087611	Liver	Cirrhotic	lipid localization	147/4634	448/18723	6.24e-05	7.12e-04	147
GO:000686911	Liver	Cirrhotic	lipid transport	128/4634	398/18723	4.54e-04	3.69e-03	128
GO:0006787	Liver	Cirrhotic	porphyrin-containing compound catabolic process	8/4634	12/18723	2.59e-03	1.53e-02	8
GO:0033015	Liver	Cirrhotic	tetrapyrrole catabolic process	8/4634	12/18723	2.59e-03	1.53e-02	8
GO:0033013	Liver	Cirrhotic	tetrapyrrole metabolic process	24/4634	59/18723	5.06e-03	2.62e-02	24

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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

SLCO2B1

SNV

Missense_Mutation

novel

c.532N>A

p.Ser178Thr

p.S178T

protein_coding

tolerated(0.43)

possibly_damaging(0.69)

TCGA-A2-A3XV-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

SLCO2B1

SNV

Missense_Mutation

rs769193802

c.1245N>G

p.Cys415Trp

p.C415W

protein_coding

deleterious(0)

possibly_damaging(0.882)

TCGA-AN-A0XR-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

SLCO2B1

SNV

Missense_Mutation

c.556N>A

p.Leu186Met

p.L186M

protein_coding

tolerated(0.24)

benign(0.248)

TCGA-AO-A0J3-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cyclophosphamide

SLCO2B1

SNV

Missense_Mutation

rs750167927

c.497N>T

p.Ser166Leu

p.S166L

protein_coding

tolerated(0.36)

benign(0.007)

TCGA-D8-A1XS-01

Breast

breast invasive carcinoma

Male

<65

III/IV

Chemotherapy

adriamycin+cyclophosphamide

SLCO2B1

SNV

Missense_Mutation

c.1834N>T

p.Met612Leu

p.M612L

protein_coding

tolerated(0.77)

benign(0.275)

TCGA-E2-A15O-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

SLCO2B1

insertion

In_Frame_Ins

novel

c.1257_1258insGAACAAGGGCCAGGCATAGTGGCTCACGTC

p.Pro419_Ser420insGluGlnGlyProGlyIleValAlaHisVal

p.P419_S420insEQGPGIVAHV

protein_coding

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

SLCO2B1

deletion

In_Frame_Del

c.1080_1109delNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN

p.Arg362_Pro371del

p.R362_P371del

protein_coding

TCGA-C8-A12L-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SLCO2B1

SNV

Missense_Mutation

rs551118953

c.154G>A

p.Val52Ile

p.V52I

protein_coding

deleterious(0.04)

benign(0.078)

TCGA-A6-2686-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

SLCO2B1

SNV

Missense_Mutation

novel

c.1516C>T

p.Pro506Ser

p.P506S

protein_coding

tolerated(0.49)

benign(0.012)

TCGA-A6-6781-01

Colorectum

colon adenocarcinoma

Male

<65

III/IV

Chemotherapy

oxaliplatin

SLCO2B1

SNV

Missense_Mutation

c.538N>C

p.Tyr180His

p.Y180H

protein_coding

tolerated(0.58)

benign(0.003)

TCGA-AA-3492-01

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
11309	SLCO2B1	TRANSPORTER, DRUGGABLE GENOME	inhibitor	178101619	ERLOTINIB
11309	SLCO2B1	TRANSPORTER, DRUGGABLE GENOME		rosuvastatin	ROSUVASTATIN
11309	SLCO2B1	TRANSPORTER, DRUGGABLE GENOME	inhibitor	135650306	GLYBURIDE
11309	SLCO2B1	TRANSPORTER, DRUGGABLE GENOME		hmg coa reductase inhibitors
11309	SLCO2B1	TRANSPORTER, DRUGGABLE GENOME	inhibitor	178102814	VERLUKAST
11309	SLCO2B1	TRANSPORTER, DRUGGABLE GENOME		ISOSILYBIN B	ISOSILYBIN B	23401473
11309	SLCO2B1	TRANSPORTER, DRUGGABLE GENOME		ELTROMBOPAG	ELTROMBOPAG	21422191
11309	SLCO2B1	TRANSPORTER, DRUGGABLE GENOME		SILIBININ	SILIBININ	23401473
11309	SLCO2B1	TRANSPORTER, DRUGGABLE GENOME		fluvastatin	FLUVASTATIN
11309	SLCO2B1	TRANSPORTER, DRUGGABLE GENOME		SULFOBROMOPHTHALEIN	SULFOBROMOPHTHALEIN	21422191

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