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: CYP2A6

Gene summary for CYP2A6

Gene summary.

Gene information	Species	Human
	Gene symbol	CYP2A6
	Gene ID	1548
	Gene name	cytochrome P450 family 2 subfamily A member 6
	Gene Alias	CPA6
	Cytomap	19q13.2
	Gene Type	protein-coding
	GO ID	GO:0001676
	UniProtAcc	P11509

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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
1548	CYP2A6	NAFLD1	Human	Liver	NAFLD	4.41e-13	1.07e+00	-0.04
1548	CYP2A6	S41	Human	Liver	Cirrhotic	2.51e-03	6.19e-01	-0.0343
1548	CYP2A6	S43	Human	Liver	Cirrhotic	8.90e-06	-2.39e-01	-0.0187
1548	CYP2A6	HCC1_Meng	Human	Liver	HCC	7.47e-09	-2.68e-01	0.0246
1548	CYP2A6	HCC2_Meng	Human	Liver	HCC	1.05e-09	-2.77e-01	0.0107
1548	CYP2A6	cirrhotic1	Human	Liver	Cirrhotic	2.32e-08	-2.73e-01	0.0202
1548	CYP2A6	cirrhotic2	Human	Liver	Cirrhotic	1.08e-03	-2.51e-01	0.0201
1548	CYP2A6	cirrhotic3	Human	Liver	Cirrhotic	1.33e-03	-2.77e-01	0.0215
1548	CYP2A6	Pt13.a	Human	Liver	HCC	7.13e-03	-2.19e-01	0.021
1548	CYP2A6	Pt13.b	Human	Liver	HCC	2.31e-09	-6.57e-02	0.0251
1548	CYP2A6	Pt14.d	Human	Liver	HCC	2.02e-04	-2.42e-01	0.0143

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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:00066316	Liver	NAFLD	fatty acid metabolic process	92/1882	390/18723	3.38e-15	3.29e-12	92
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:00467006	Liver	NAFLD	heterocycle catabolic process	92/1882	445/18723	1.16e-11	4.52e-09	92
GO:00082023	Liver	NAFLD	steroid metabolic process	69/1882	319/18723	5.90e-10	1.28e-07	69
GO:00094107	Liver	NAFLD	response to xenobiotic stimulus	88/1882	462/18723	2.53e-09	4.11e-07	88
GO:00714663	Liver	NAFLD	cellular response to xenobiotic stimulus	33/1882	177/18723	3.54e-04	5.36e-03	33
GO:00335596	Liver	NAFLD	unsaturated fatty acid metabolic process	24/1882	116/18723	4.64e-04	6.74e-03	24
GO:00016763	Liver	NAFLD	long-chain fatty acid metabolic process	23/1882	112/18723	6.73e-04	8.66e-03	23
GO:01202545	Liver	NAFLD	olefinic compound metabolic process	28/1882	153/18723	1.28e-03	1.45e-02	28
GO:00068054	Liver	NAFLD	xenobiotic metabolic process	22/1882	111/18723	1.42e-03	1.58e-02	22
GO:00066906	Liver	NAFLD	icosanoid metabolic process	22/1882	123/18723	5.33e-03	4.11e-02	22
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:004670011	Liver	Cirrhotic	heterocycle catabolic process	192/4634	445/18723	7.17e-18	1.12e-15	192
GO:000820211	Liver	Cirrhotic	steroid metabolic process	143/4634	319/18723	2.79e-15	3.18e-13	143
GO:000663112	Liver	Cirrhotic	fatty acid metabolic process	165/4634	390/18723	1.29e-14	1.26e-12	165
GO:000941012	Liver	Cirrhotic	response to xenobiotic stimulus	165/4634	462/18723	6.82e-08	2.09e-06	165
GO:00714661	Liver	Cirrhotic	cellular response to xenobiotic stimulus	66/4634	177/18723	1.34e-04	1.31e-03	66
GO:000680511	Liver	Cirrhotic	xenobiotic metabolic process	43/4634	111/18723	7.51e-04	5.54e-03	43

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0541714	Liver	NAFLD	Lipid and atherosclerosis	42/1043	215/8465	1.46e-03	1.71e-02	1.38e-02	42
hsa0541715	Liver	NAFLD	Lipid and atherosclerosis	42/1043	215/8465	1.46e-03	1.71e-02	1.38e-02	42
hsa00983	Liver	Cirrhotic	Drug metabolism - other enzymes	34/2530	80/8465	1.08e-02	3.57e-02	2.20e-02	34
hsa0541722	Liver	Cirrhotic	Lipid and atherosclerosis	80/2530	215/8465	1.18e-02	3.81e-02	2.35e-02	80
hsa009831	Liver	Cirrhotic	Drug metabolism - other enzymes	34/2530	80/8465	1.08e-02	3.57e-02	2.20e-02	34
hsa0541732	Liver	Cirrhotic	Lipid and atherosclerosis	80/2530	215/8465	1.18e-02	3.81e-02	2.35e-02	80
hsa009832	Liver	HCC	Drug metabolism - other enzymes	54/4020	80/8465	2.25e-04	1.09e-03	6.08e-04	54
hsa0541742	Liver	HCC	Lipid and atherosclerosis	118/4020	215/8465	1.66e-02	3.92e-02	2.18e-02	118
hsa009833	Liver	HCC	Drug metabolism - other enzymes	54/4020	80/8465	2.25e-04	1.09e-03	6.08e-04	54
hsa0541752	Liver	HCC	Lipid and atherosclerosis	118/4020	215/8465	1.66e-02	3.92e-02	2.18e-02	118

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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

CYP2A6

SNV

Missense_Mutation

c.1091N>C

p.Asp364Ala

p.D364A

P11509

protein_coding

deleterious(0.04)

probably_damaging(0.993)

TCGA-AN-A0AM-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CYP2A6

SNV

Missense_Mutation

c.1082G>C

p.Arg361Thr

p.R361T

P11509

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AO-A0J9-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

CYP2A6

SNV

Missense_Mutation

novel

c.475N>A

p.Ala159Thr

p.A159T

P11509

protein_coding

tolerated(0.08)

benign(0.009)

TCGA-BH-A0HA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CYP2A6

SNV

Missense_Mutation

novel

c.840N>T

p.Lys280Asn

p.K280N

P11509

protein_coding

tolerated(0.57)

benign(0.003)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CYP2A6

SNV

Missense_Mutation

c.778G>A

p.Asp260Asn

p.D260N

P11509

protein_coding

deleterious(0.02)

probably_damaging(0.923)

TCGA-C5-A7UH-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

CYP2A6

SNV

Missense_Mutation

novel

c.674N>T

p.Ser225Leu

p.S225L

P11509

protein_coding

tolerated(0.2)

possibly_damaging(0.572)

TCGA-EK-A2RA-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

CYP2A6

SNV

Missense_Mutation

rs748123859

c.1467N>T

p.Met489Ile

p.M489I

P11509

protein_coding

tolerated(0.36)

benign(0.006)

TCGA-JX-A3Q0-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

CYP2A6

SNV

Missense_Mutation

rs757892208

c.1217C>G

p.Ser406Cys

p.S406C

P11509

protein_coding

tolerated(0.1)

benign(0.029)

TCGA-Q1-A5R2-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CYP2A6

SNV

Missense_Mutation

c.307N>A

p.Glu103Lys

p.E103K

P11509

protein_coding

tolerated(0.64)

benign(0.003)

TCGA-VS-A9V1-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CYP2A6

insertion

Frame_Shift_Ins

novel

c.726_727insA

p.Gly243ArgfsTer27

p.G243Rfs*27

P11509

protein_coding

TCGA-VS-A94Z-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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
1548	CYP2A6	ENZYME, DRUGGABLE GENOME, CYTOCHROME P450		artesunate	ARTESUNATE	18064444,18979093,19926036,19851082,18350255,12920490,12844133
1548	CYP2A6	ENZYME, DRUGGABLE GENOME, CYTOCHROME P450		BENZO[B]THIOPHEN-2-YLMETHANAMINE	CHEMBL1770735	25458499
1548	CYP2A6	ENZYME, DRUGGABLE GENOME, CYTOCHROME P450		halothane	HALOTHANE	12386121,19702528,19442086,11038165,14704462,8886611
1548	CYP2A6	ENZYME, DRUGGABLE GENOME, CYTOCHROME P450		zidovudine	ZIDOVUDINE	22960662
1548	CYP2A6	ENZYME, DRUGGABLE GENOME, CYTOCHROME P450	inhibitor	252827412
1548	CYP2A6	ENZYME, DRUGGABLE GENOME, CYTOCHROME P450		acetaminophen	ACETAMINOPHEN	26049587,11866476,9548799
1548	CYP2A6	ENZYME, DRUGGABLE GENOME, CYTOCHROME P450		bupropion	BUPROPION	26132489
1548	CYP2A6	ENZYME, DRUGGABLE GENOME, CYTOCHROME P450		coumarin	COUMARIN	11394901,16679388,10544257,14583682,10923861,9827545,27339126,16041240,15900015,12325023,12844137,9409631,21521021,15993850,11779172,2322567,11278503,11038160
1548	CYP2A6	ENZYME, DRUGGABLE GENOME, CYTOCHROME P450		3-FORMYLINDOLE	3-FORMYLINDOLE	25458499
1548	CYP2A6	ENZYME, DRUGGABLE GENOME, CYTOCHROME P450		arteether		18064444,18979093,19926036,19851082,18350255,12920490,12844133

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