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: ABCC3

Gene summary for ABCC3

Gene summary.

Gene information	Species	Human
	Gene symbol	ABCC3
	Gene ID	8714
	Gene name	ATP binding cassette subfamily C member 3
	Gene Alias	ABC31
	Cytomap	17q21.33
	Gene Type	protein-coding
	GO ID	GO:0003008
	UniProtAcc	O15438

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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
8714	ABCC3	HTA11_2487_2000001011	Human	Colorectum	SER	2.25e-19	1.36e+00	-0.1808
8714	ABCC3	HTA11_1938_2000001011	Human	Colorectum	AD	1.39e-41	1.55e+00	-0.0811
8714	ABCC3	HTA11_78_2000001011	Human	Colorectum	AD	5.63e-17	9.98e-01	-0.1088
8714	ABCC3	HTA11_347_2000001011	Human	Colorectum	AD	1.32e-53	1.58e+00	-0.1954
8714	ABCC3	HTA11_411_2000001011	Human	Colorectum	SER	3.88e-11	1.35e+00	-0.2602
8714	ABCC3	HTA11_2112_2000001011	Human	Colorectum	SER	4.17e-11	9.93e-01	-0.2196
8714	ABCC3	HTA11_3361_2000001011	Human	Colorectum	AD	1.24e-16	9.02e-01	-0.1207
8714	ABCC3	HTA11_83_2000001011	Human	Colorectum	SER	5.90e-38	1.52e+00	-0.1526
8714	ABCC3	HTA11_696_2000001011	Human	Colorectum	AD	9.95e-16	1.15e+00	-0.1464
8714	ABCC3	HTA11_866_2000001011	Human	Colorectum	AD	2.47e-27	1.15e+00	-0.1001
8714	ABCC3	HTA11_1391_2000001011	Human	Colorectum	AD	4.48e-15	1.44e+00	-0.059
8714	ABCC3	HTA11_2992_2000001011	Human	Colorectum	SER	6.35e-15	9.63e-01	-0.1706
8714	ABCC3	HTA11_5212_2000001011	Human	Colorectum	AD	1.51e-02	3.74e-01	-0.2061
8714	ABCC3	HTA11_5216_2000001011	Human	Colorectum	SER	4.77e-05	6.33e-01	-0.1462
8714	ABCC3	HTA11_546_2000001011	Human	Colorectum	AD	1.17e-10	9.17e-01	-0.0842
8714	ABCC3	HTA11_4255_2000001011	Human	Colorectum	SER	3.31e-03	5.01e-01	0.0446
8714	ABCC3	HTA11_8622_2000001021	Human	Colorectum	SER	7.48e-05	6.17e-01	0.0528
8714	ABCC3	HTA11_10623_2000001011	Human	Colorectum	AD	1.00e-08	8.12e-01	-0.0177
8714	ABCC3	HTA11_10711_2000001011	Human	Colorectum	AD	8.85e-03	4.75e-01	0.0338
8714	ABCC3	HTA11_7696_3000711011	Human	Colorectum	AD	1.33e-02	4.05e-01	0.0674

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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
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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
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: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:0015698	Colorectum	AD	inorganic anion transport	52/3918	180/18723	6.83e-03	4.22e-02	52
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: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:00102321	Colorectum	FAP	vascular transport	25/2622	88/18723	3.19e-04	4.12e-03	25
GO:0003018	Colorectum	FAP	vascular process in circulatory system	56/2622	263/18723	7.67e-04	8.12e-03	56
GO:00108762	Colorectum	FAP	lipid localization	85/2622	448/18723	1.92e-03	1.63e-02	85
GO:00156981	Colorectum	FAP	inorganic anion transport	38/2622	180/18723	5.73e-03	3.67e-02	38
GO:00030181	Colorectum	CRC	vascular process in circulatory system	45/2078	263/18723	2.10e-03	2.08e-02	45
GO:00068692	Colorectum	CRC	lipid transport	63/2078	398/18723	2.36e-03	2.26e-02	63
GO:00108763	Colorectum	CRC	lipid localization	68/2078	448/18723	4.60e-03	3.58e-02	68
GO:01501042	Colorectum	CRC	transport across blood-brain barrier	18/2078	87/18723	6.50e-03	4.69e-02	18
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

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa04976	Colorectum	FAP	Bile secretion	24/1404	89/8465	8.76e-03	3.21e-02	1.96e-02	24
hsa049761	Colorectum	FAP	Bile secretion	24/1404	89/8465	8.76e-03	3.21e-02	1.96e-02	24
hsa015232	Esophagus	ESCC	Antifolate resistance	22/4205	30/8465	7.23e-03	1.76e-02	8.99e-03	22
hsa0152311	Esophagus	ESCC	Antifolate resistance	22/4205	30/8465	7.23e-03	1.76e-02	8.99e-03	22
hsa02010	Liver	NAFLD	ABC transporters	16/1043	45/8465	4.97e-05	1.16e-03	9.37e-04	16
hsa049762	Liver	NAFLD	Bile secretion	20/1043	89/8465	5.08e-03	4.43e-02	3.57e-02	20
hsa020101	Liver	NAFLD	ABC transporters	16/1043	45/8465	4.97e-05	1.16e-03	9.37e-04	16
hsa0497611	Liver	NAFLD	Bile secretion	20/1043	89/8465	5.08e-03	4.43e-02	3.57e-02	20
hsa01523	Liver	HCC	Antifolate resistance	21/4020	30/8465	1.06e-02	2.71e-02	1.51e-02	21
hsa020102	Liver	HCC	ABC transporters	29/4020	45/8465	1.62e-02	3.88e-02	2.16e-02	29
hsa015231	Liver	HCC	Antifolate resistance	21/4020	30/8465	1.06e-02	2.71e-02	1.51e-02	21
hsa020103	Liver	HCC	ABC transporters	29/4020	45/8465	1.62e-02	3.88e-02	2.16e-02	29

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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

ABCC3

SNV

Missense_Mutation

novel

c.2348N>G

p.Ser783Cys

p.S783C

O15438

protein_coding

deleterious(0)

possibly_damaging(0.778)

TCGA-3C-AALI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Poly E

Complete Response

ABCC3

SNV

Missense_Mutation

c.2531C>G

p.Ser844Cys

p.S844C

O15438

protein_coding

deleterious(0.01)

possibly_damaging(0.625)

TCGA-A8-A0A7-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ABCC3

SNV

Missense_Mutation

novel

c.2877N>A

p.Phe959Leu

p.F959L

O15438

protein_coding

deleterious(0.01)

benign(0.188)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ABCC3

SNV

Missense_Mutation

c.2521N>A

p.Arg841Ser

p.R841S

O15438

protein_coding

tolerated(0.17)

benign(0.057)

TCGA-AR-A255-01

Breast

breast invasive carcinoma

Female

<65

I/II

Targeted Molecular therapy

trastuzumab

ABCC3

SNV

Missense_Mutation

c.2213N>T

p.Gly738Val

p.G738V

O15438

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-BH-A0BZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

ABCC3

SNV

Missense_Mutation

novel

c.2383N>T

p.Gly795Trp

p.G795W

O15438

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-E9-A1NC-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

ABCC3

SNV

Missense_Mutation

c.3560C>G

p.Pro1187Arg

p.P1187R

O15438

protein_coding

deleterious(0)

possibly_damaging(0.845)

TCGA-E9-A247-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

ABCC3

SNV

Missense_Mutation

rs755779050

c.2273G>A

p.Arg758Gln

p.R758Q

O15438

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-GM-A3NY-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

ABCC3

SNV

Missense_Mutation

novel

c.4207C>T

p.His1403Tyr

p.H1403Y

O15438

protein_coding

deleterious(0)

probably_damaging(0.915)

TCGA-PL-A8LX-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

ABCC3

deletion

Frame_Shift_Del

novel

c.3421delN

p.Ser1141GlnfsTer15

p.S1141Qfs*15

O15438

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

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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
8714	ABCC3	DRUG RESISTANCE, DRUGGABLE GENOME, TRANSPORTER, ABC TRANSPORTER, CLINICALLY ACTIONABLE		EMTRICITABINE	EMTRICITABINE	17172311
8714	ABCC3	DRUG RESISTANCE, DRUGGABLE GENOME, TRANSPORTER, ABC TRANSPORTER, CLINICALLY ACTIONABLE		MONOMETHYL AURISTATIN E		18593940
8714	ABCC3	DRUG RESISTANCE, DRUGGABLE GENOME, TRANSPORTER, ABC TRANSPORTER, CLINICALLY ACTIONABLE		methotrexate	METHOTREXATE	22016816,21317831,21606946
8714	ABCC3	DRUG RESISTANCE, DRUGGABLE GENOME, TRANSPORTER, ABC TRANSPORTER, CLINICALLY ACTIONABLE		CEFOPERAZONE	CEFOPERAZONE	22166395
8714	ABCC3	DRUG RESISTANCE, DRUGGABLE GENOME, TRANSPORTER, ABC TRANSPORTER, CLINICALLY ACTIONABLE		DOXORUBICIN	DOXORUBICIN
8714	ABCC3	DRUG RESISTANCE, DRUGGABLE GENOME, TRANSPORTER, ABC TRANSPORTER, CLINICALLY ACTIONABLE		ABACAVIR	ABACAVIR	17172311
8714	ABCC3	DRUG RESISTANCE, DRUGGABLE GENOME, TRANSPORTER, ABC TRANSPORTER, CLINICALLY ACTIONABLE		CEFACLOR	CEFACLOR	22166395
8714	ABCC3	DRUG RESISTANCE, DRUGGABLE GENOME, TRANSPORTER, ABC TRANSPORTER, CLINICALLY ACTIONABLE		TENOFOVIR	TENOFOVIR	17172311
8714	ABCC3	DRUG RESISTANCE, DRUGGABLE GENOME, TRANSPORTER, ABC TRANSPORTER, CLINICALLY ACTIONABLE		DELAVIRDINE	DELAVIRDINE	17172311
8714	ABCC3	DRUG RESISTANCE, DRUGGABLE GENOME, TRANSPORTER, ABC TRANSPORTER, CLINICALLY ACTIONABLE		cisplatin	CISPLATIN	25141953,22016816,31666714,27457817

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