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: ABCC1

Gene summary for ABCC1

Gene summary.

Gene information	Species	Human
	Gene symbol	ABCC1
	Gene ID	4363
	Gene name	ATP binding cassette subfamily C member 1
	Gene Alias	ABC29
	Cytomap	16p13.11
	Gene Type	protein-coding
	GO ID	GO:0003008
	UniProtAcc	P33527

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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
4363	ABCC1	CCI_1	Human	Cervix	CC	4.31e-13	8.82e-01	0.528
4363	ABCC1	CCI_2	Human	Cervix	CC	5.77e-07	6.57e-01	0.5249
4363	ABCC1	CCI_3	Human	Cervix	CC	7.40e-14	8.29e-01	0.516
4363	ABCC1	HTA11_3410_2000001011	Human	Colorectum	AD	6.85e-03	5.79e-02	0.0155
4363	ABCC1	HTA11_1391_2000001011	Human	Colorectum	AD	8.75e-10	1.08e+00	-0.059
4363	ABCC1	HTA11_866_3004761011	Human	Colorectum	AD	2.01e-02	4.61e-01	0.096
4363	ABCC1	HTA11_7696_3000711011	Human	Colorectum	AD	8.52e-03	5.09e-01	0.0674
4363	ABCC1	HTA11_99999965104_69814	Human	Colorectum	MSS	7.52e-06	8.68e-01	0.281
4363	ABCC1	HTA11_99999971662_82457	Human	Colorectum	MSS	1.18e-06	7.01e-01	0.3859
4363	ABCC1	HTA11_99999973899_84307	Human	Colorectum	MSS	1.64e-05	1.02e+00	0.2585
4363	ABCC1	HTA11_99999974143_84620	Human	Colorectum	MSS	4.10e-05	4.88e-01	0.3005
4363	ABCC1	A015-C-203	Human	Colorectum	FAP	4.57e-10	7.91e-02	-0.1294
4363	ABCC1	A002-C-201	Human	Colorectum	FAP	3.76e-04	3.17e-01	0.0324
4363	ABCC1	A001-C-108	Human	Colorectum	FAP	6.13e-04	1.44e-01	-0.0272
4363	ABCC1	A002-C-021	Human	Colorectum	FAP	6.97e-06	4.48e-01	0.1171
4363	ABCC1	A002-C-205	Human	Colorectum	FAP	7.87e-11	2.92e-01	-0.1236
4363	ABCC1	A015-C-006	Human	Colorectum	FAP	1.22e-04	9.83e-04	-0.0994
4363	ABCC1	A015-C-106	Human	Colorectum	FAP	3.56e-02	2.32e-01	-0.0511
4363	ABCC1	A002-C-114	Human	Colorectum	FAP	1.89e-05	8.51e-02	-0.1561
4363	ABCC1	A015-C-104	Human	Colorectum	FAP	3.71e-12	1.01e-01	-0.1899

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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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
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:000697910	Cervix	CC	response to oxidative stress	102/2311	446/18723	2.99e-10	4.36e-08	102
GO:00321035	Cervix	CC	positive regulation of response to external stimulus	95/2311	427/18723	5.44e-09	5.03e-07	95
GO:00603267	Cervix	CC	cell chemotaxis	73/2311	310/18723	2.82e-08	1.96e-06	73
GO:006219710	Cervix	CC	cellular response to chemical stress	76/2311	337/18723	1.01e-07	5.25e-06	76
GO:003459910	Cervix	CC	cellular response to oxidative stress	63/2311	288/18723	3.58e-06	9.50e-05	63
GO:00313494	Cervix	CC	positive regulation of defense response	60/2311	278/18723	9.38e-06	2.11e-04	60
GO:19016538	Cervix	CC	cellular response to peptide	72/2311	359/18723	1.89e-05	3.48e-04	72
GO:00507273	Cervix	CC	regulation of inflammatory response	75/2311	386/18723	3.95e-05	6.18e-04	75
GO:00507294	Cervix	CC	positive regulation of inflammatory response	34/2311	142/18723	9.51e-05	1.25e-03	34
GO:00467008	Cervix	CC	heterocycle catabolic process	80/2311	445/18723	3.23e-04	3.42e-03	80
GO:00442709	Cervix	CC	cellular nitrogen compound catabolic process	79/2311	451/18723	7.80e-04	6.91e-03	79
GO:00194398	Cervix	CC	aromatic compound catabolic process	79/2311	467/18723	2.14e-03	1.54e-02	79
GO:00094109	Cervix	CC	response to xenobiotic stimulus	78/2311	462/18723	2.39e-03	1.70e-02	78
GO:19013618	Cervix	CC	organic cyclic compound catabolic process	80/2311	495/18723	6.77e-03	3.72e-02	80
GO:00158337	Cervix	CC	peptide transport	46/2311	264/18723	9.69e-03	4.78e-02	46
GO:0044270	Colorectum	AD	cellular nitrogen compound catabolic process	147/3918	451/18723	3.35e-09	2.23e-07	147
GO:0046700	Colorectum	AD	heterocycle catabolic process	145/3918	445/18723	4.37e-09	2.84e-07	145
GO:0006979	Colorectum	AD	response to oxidative stress	145/3918	446/18723	5.16e-09	3.23e-07	145
GO:0019439	Colorectum	AD	aromatic compound catabolic process	146/3918	467/18723	7.48e-08	3.84e-06	146
GO:1901361	Colorectum	AD	organic cyclic compound catabolic process	153/3918	495/18723	8.23e-08	4.18e-06	153

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0407110	Cervix	CC	Sphingolipid signaling pathway	35/1267	121/8465	5.70e-05	3.93e-04	2.32e-04	35
hsa0407113	Cervix	CC	Sphingolipid signaling pathway	35/1267	121/8465	5.70e-05	3.93e-04	2.32e-04	35
hsa040712	Colorectum	MSS	Sphingolipid signaling pathway	40/1875	121/8465	3.56e-03	1.64e-02	1.01e-02	40
hsa040713	Colorectum	MSS	Sphingolipid signaling pathway	40/1875	121/8465	3.56e-03	1.64e-02	1.01e-02	40
hsa040714	Colorectum	FAP	Sphingolipid signaling pathway	34/1404	121/8465	9.53e-04	5.22e-03	3.17e-03	34
hsa040715	Colorectum	FAP	Sphingolipid signaling pathway	34/1404	121/8465	9.53e-04	5.22e-03	3.17e-03	34
hsa040716	Colorectum	CRC	Sphingolipid signaling pathway	30/1091	121/8465	2.49e-04	3.09e-03	2.09e-03	30
hsa040717	Colorectum	CRC	Sphingolipid signaling pathway	30/1091	121/8465	2.49e-04	3.09e-03	2.09e-03	30

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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

ABCC1

SNV

Missense_Mutation

c.1390N>G

p.Pro464Ala

p.P464A

P33527

protein_coding

deleterious(0.04)

benign(0.4)

TCGA-AN-A0AR-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ABCC1

SNV

Missense_Mutation

rs377634982

c.870N>C

p.Lys290Asn

p.K290N

P33527

protein_coding

tolerated(0.25)

benign(0)

TCGA-AN-A0XU-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ABCC1

SNV

Missense_Mutation

c.3622N>G

p.Asn1208Asp

p.N1208D

P33527

protein_coding

deleterious(0.01)

probably_damaging(0.999)

TCGA-BH-A0HA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ABCC1

SNV

Missense_Mutation

c.4085G>A

p.Gly1362Asp

p.G1362D

P33527

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ABCC1

SNV

Missense_Mutation

rs756405833

c.3781G>A

p.Val1261Met

p.V1261M

P33527

protein_coding

deleterious(0)

possibly_damaging(0.777)

TCGA-D8-A13Z-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine

ABCC1

SNV

Missense_Mutation

novel

c.1664N>T

p.Cys555Phe

p.C555F

P33527

protein_coding

deleterious(0.03)

probably_damaging(0.926)

TCGA-E9-A244-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

ABCC1

SNV

Missense_Mutation

c.1207N>T

p.Val403Phe

p.V403F

P33527

protein_coding

deleterious(0)

possibly_damaging(0.905)

TCGA-GM-A2DM-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxol

ABCC1

insertion

In_Frame_Ins

novel

c.631_632insACCCAGGCTGGAGTGCGATGGCACAATCTCAGCTTGCTGCAA

p.Ser211delinsTyrProGlyTrpSerAlaMetAlaGlnSerGlnLeuAlaAlaThr

p.S211delinsYPGWSAMAQSQLAAT

P33527

protein_coding

TCGA-A2-A04Y-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

ABCC1

insertion

Frame_Shift_Ins

novel

c.946_947insGTCATCATCACAGTCAATTTTATTTATT

p.Val316GlyfsTer49

p.V316Gfs*49

P33527

protein_coding

TCGA-AO-A03T-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

ABCC1

insertion

Frame_Shift_Ins

novel

c.3318_3319insACCATGCCTGGTTCATCATTATTATTATTATT

p.Val1107ThrfsTer45

p.V1107Tfs*45

P33527

protein_coding

TCGA-BH-A0AW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

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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
4363	ABCC1	DRUGGABLE GENOME, TRANSPORTER, ABC TRANSPORTER		NEVIRAPINE	NEVIRAPINE	17172311
4363	ABCC1	DRUGGABLE GENOME, TRANSPORTER, ABC TRANSPORTER	inhibitor	384403652
4363	ABCC1	DRUGGABLE GENOME, TRANSPORTER, ABC TRANSPORTER		TRAIL		10811986
4363	ABCC1	DRUGGABLE GENOME, TRANSPORTER, ABC TRANSPORTER		(S)-VERAPAMIL	(S)-VERAPAMIL	17646169
4363	ABCC1	DRUGGABLE GENOME, TRANSPORTER, ABC TRANSPORTER		Benzbromarone	BENZBROMARONE
4363	ABCC1	DRUGGABLE GENOME, TRANSPORTER, ABC TRANSPORTER		ERYTHROMYCIN	ERYTHROMYCIN	10817732
4363	ABCC1	DRUGGABLE GENOME, TRANSPORTER, ABC TRANSPORTER		EPIPODOPHYLLOTOXINS		9719484
4363	ABCC1	DRUGGABLE GENOME, TRANSPORTER, ABC TRANSPORTER		NOVOBIOCIN	NOVOBIOCIN	10901300
4363	ABCC1	DRUGGABLE GENOME, TRANSPORTER, ABC TRANSPORTER		TENOFOVIR	TENOFOVIR	17172311
4363	ABCC1	DRUGGABLE GENOME, TRANSPORTER, ABC TRANSPORTER		CYCLOSPORINE	CYCLOSPORINE	23017888

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