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: NOX1

Gene summary for NOX1

Gene summary.

Gene information	Species	Human
	Gene symbol	NOX1
	Gene ID	27035
	Gene name	NADPH oxidase 1
	Gene Alias	GP91-2
	Cytomap	Xq22.1
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	A6NGA6

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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
27035	NOX1	HTA11_3410_2000001011	Human	Colorectum	AD	1.78e-02	-2.88e-01	0.0155
27035	NOX1	HTA11_2487_2000001011	Human	Colorectum	SER	1.51e-08	-6.47e-01	-0.1808
27035	NOX1	HTA11_3361_2000001011	Human	Colorectum	AD	1.71e-05	-5.71e-01	-0.1207
27035	NOX1	HTA11_7862_2000001011	Human	Colorectum	AD	5.81e-04	5.61e-01	-0.0179
27035	NOX1	HTA11_7663_2000001011	Human	Colorectum	SER	3.80e-03	-7.66e-01	0.0131
27035	NOX1	HTA11_10711_2000001011	Human	Colorectum	AD	1.39e-05	-5.97e-01	0.0338
27035	NOX1	HTA11_99999970781_79442	Human	Colorectum	MSS	4.99e-02	-3.28e-01	0.294
27035	NOX1	HTA11_99999965104_69814	Human	Colorectum	MSS	8.45e-11	8.84e-01	0.281
27035	NOX1	HTA11_99999973899_84307	Human	Colorectum	MSS	3.71e-03	-5.32e-01	0.2585
27035	NOX1	HTA11_99999974143_84620	Human	Colorectum	MSS	1.19e-02	-3.65e-01	0.3005
27035	NOX1	A002-C-010	Human	Colorectum	FAP	1.78e-07	4.90e-01	0.242
27035	NOX1	A001-C-207	Human	Colorectum	FAP	5.83e-03	-2.70e-01	0.1278
27035	NOX1	A015-C-203	Human	Colorectum	FAP	8.23e-22	2.27e-01	-0.1294
27035	NOX1	A015-C-204	Human	Colorectum	FAP	3.86e-02	8.75e-02	-0.0228
27035	NOX1	A014-C-040	Human	Colorectum	FAP	8.00e-15	8.24e-01	-0.1184
27035	NOX1	A002-C-201	Human	Colorectum	FAP	1.48e-13	3.82e-01	0.0324
27035	NOX1	A002-C-203	Human	Colorectum	FAP	4.33e-05	4.20e-01	0.2786
27035	NOX1	A001-C-119	Human	Colorectum	FAP	4.22e-04	-7.64e-02	-0.1557
27035	NOX1	A001-C-108	Human	Colorectum	FAP	5.01e-11	7.48e-02	-0.0272
27035	NOX1	A002-C-021	Human	Colorectum	FAP	3.57e-10	5.18e-01	0.1171

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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

∗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:00328723	Colorectum	CRC	regulation of stress-activated MAPK cascade	40/2078	192/18723	6.11e-05	1.35e-03	40
GO:00463281	Colorectum	CRC	regulation of JNK cascade	30/2078	133/18723	1.11e-04	2.20e-03	30
GO:00345995	Colorectum	CRC	cellular response to oxidative stress	53/2078	288/18723	1.47e-04	2.68e-03	53
GO:00069795	Colorectum	CRC	response to oxidative stress	73/2078	446/18723	4.31e-04	6.34e-03	73
GO:20012425	Colorectum	CRC	regulation of intrinsic apoptotic signaling pathway	33/2078	164/18723	5.00e-04	7.11e-03	33
GO:19004075	Colorectum	CRC	regulation of cellular response to oxidative stress	21/2078	89/18723	6.03e-04	8.06e-03	21
GO:00086315	Colorectum	CRC	intrinsic apoptotic signaling pathway in response to oxidative stress	13/2078	45/18723	8.91e-04	1.10e-02	13
GO:19028825	Colorectum	CRC	regulation of response to oxidative stress	22/2078	98/18723	9.29e-04	1.14e-02	22
GO:20012335	Colorectum	CRC	regulation of apoptotic signaling pathway	59/2078	356/18723	1.07e-03	1.25e-02	59
GO:00364735	Colorectum	CRC	cell death in response to oxidative stress	21/2078	95/18723	1.48e-03	1.58e-02	21
GO:00704824	Colorectum	CRC	response to oxygen levels	56/2078	347/18723	2.60e-03	2.40e-02	56
GO:19032015	Colorectum	CRC	regulation of oxidative stress-induced cell death	17/2078	74/18723	2.61e-03	2.40e-02	17
GO:00514533	Colorectum	CRC	regulation of intracellular pH	17/2078	75/18723	3.04e-03	2.71e-02	17
GO:19021755	Colorectum	CRC	regulation of oxidative stress-induced intrinsic apoptotic signaling pathway	9/2078	29/18723	3.18e-03	2.78e-02	9
GO:00703041	Colorectum	CRC	positive regulation of stress-activated protein kinase signaling cascade	25/2078	128/18723	3.44e-03	2.92e-02	25
GO:00714534	Colorectum	CRC	cellular response to oxygen levels	32/2078	177/18723	3.69e-03	3.12e-02	32
GO:00300044	Colorectum	CRC	cellular monovalent inorganic cation homeostasis	21/2078	103/18723	4.15e-03	3.40e-02	21
GO:0043410	Colorectum	CRC	positive regulation of MAPK cascade	72/2078	480/18723	4.85e-03	3.74e-02	72
GO:00328741	Colorectum	CRC	positive regulation of stress-activated MAPK cascade	24/2078	126/18723	5.68e-03	4.26e-02	24
GO:00306414	Colorectum	CRC	regulation of cellular pH	17/2078	81/18723	6.93e-03	4.85e-02	17

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05208	Colorectum	AD	Chemical carcinogenesis - reactive oxygen species	126/2092	223/8465	1.01e-24	1.68e-22	1.07e-22	126
hsa05010	Colorectum	AD	Alzheimer disease	174/2092	384/8465	1.82e-19	9.26e-18	5.91e-18	174
hsa05022	Colorectum	AD	Pathways of neurodegeneration - multiple diseases	201/2092	476/8465	4.54e-18	1.27e-16	8.09e-17	201
hsa05418	Colorectum	AD	Fluid shear stress and atherosclerosis	54/2092	139/8465	1.41e-04	1.16e-03	7.37e-04	54
hsa05417	Colorectum	AD	Lipid and atherosclerosis	73/2092	215/8465	1.31e-03	8.27e-03	5.27e-03	73
hsa052081	Colorectum	AD	Chemical carcinogenesis - reactive oxygen species	126/2092	223/8465	1.01e-24	1.68e-22	1.07e-22	126
hsa050101	Colorectum	AD	Alzheimer disease	174/2092	384/8465	1.82e-19	9.26e-18	5.91e-18	174
hsa050221	Colorectum	AD	Pathways of neurodegeneration - multiple diseases	201/2092	476/8465	4.54e-18	1.27e-16	8.09e-17	201
hsa054181	Colorectum	AD	Fluid shear stress and atherosclerosis	54/2092	139/8465	1.41e-04	1.16e-03	7.37e-04	54
hsa054171	Colorectum	AD	Lipid and atherosclerosis	73/2092	215/8465	1.31e-03	8.27e-03	5.27e-03	73
hsa052082	Colorectum	SER	Chemical carcinogenesis - reactive oxygen species	103/1580	223/8465	1.60e-21	7.57e-20	5.50e-20	103
hsa050102	Colorectum	SER	Alzheimer disease	146/1580	384/8465	6.52e-20	2.40e-18	1.75e-18	146
hsa050222	Colorectum	SER	Pathways of neurodegeneration - multiple diseases	168/1580	476/8465	6.23e-19	2.07e-17	1.50e-17	168
hsa054182	Colorectum	SER	Fluid shear stress and atherosclerosis	40/1580	139/8465	2.28e-03	1.75e-02	1.27e-02	40
hsa054172	Colorectum	SER	Lipid and atherosclerosis	55/1580	215/8465	6.83e-03	3.77e-02	2.74e-02	55
hsa052083	Colorectum	SER	Chemical carcinogenesis - reactive oxygen species	103/1580	223/8465	1.60e-21	7.57e-20	5.50e-20	103
hsa050103	Colorectum	SER	Alzheimer disease	146/1580	384/8465	6.52e-20	2.40e-18	1.75e-18	146
hsa050223	Colorectum	SER	Pathways of neurodegeneration - multiple diseases	168/1580	476/8465	6.23e-19	2.07e-17	1.50e-17	168
hsa054183	Colorectum	SER	Fluid shear stress and atherosclerosis	40/1580	139/8465	2.28e-03	1.75e-02	1.27e-02	40
hsa054173	Colorectum	SER	Lipid and atherosclerosis	55/1580	215/8465	6.83e-03	3.77e-02	2.74e-02	55

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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

NOX1

SNV

Missense_Mutation

novel

c.802N>C

p.Glu268Gln

p.E268Q

Q9Y5S8

protein_coding

tolerated(0.58)

benign(0.001)

TCGA-A2-A4RW-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

NOX1

SNV

Missense_Mutation

rs769691003

c.776N>A

p.Arg259His

p.R259H

Q9Y5S8

protein_coding

tolerated(0.28)

benign(0)

TCGA-AR-A1AJ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NOX1

SNV

Missense_Mutation

c.1487T>G

p.Val496Gly

p.V496G

Q9Y5S8

protein_coding

deleterious(0)

possibly_damaging(0.892)

TCGA-BH-A0BT-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

NOX1

insertion

Nonsense_Mutation

rs761560592

c.155_156insATTCTGAA

p.Cys52Ter

p.C52*

Q9Y5S8

protein_coding

TCGA-A2-A0D4-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

NOX1

insertion

Nonsense_Mutation

novel

c.155_156insAA

p.Cys52Ter

p.C52*

Q9Y5S8

protein_coding

TCGA-A8-A08L-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

NOX1

insertion

Nonsense_Mutation

rs761560592

c.155_156insATTCTGAA

p.Cys52Ter

p.C52*

Q9Y5S8

protein_coding

TCGA-BH-A0C0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

NOX1

SNV

Missense_Mutation

rs772834730

c.869N>A

p.Arg290His

p.R290H

Q9Y5S8

protein_coding

deleterious(0)

probably_damaging(0.978)

TCGA-C5-A901-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

NOX1

SNV

Missense_Mutation

rs192653247

c.263N>A

p.Arg88His

p.R88H

Q9Y5S8

protein_coding

tolerated(0.34)

benign(0.112)

TCGA-EK-A3GN-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

NOX1

SNV

Missense_Mutation

rs373860304

c.218G>A

p.Arg73His

p.R73H

Q9Y5S8

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-FU-A23L-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

NOX1

SNV

Missense_Mutation

c.1012C>T

p.His338Tyr

p.H338Y

Q9Y5S8

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-FU-A3HZ-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
27035	NOX1	ION CHANNEL, ENZYME, TRANSPORTER, DRUGGABLE GENOME	inhibitor	363894229
27035	NOX1	ION CHANNEL, ENZYME, TRANSPORTER, DRUGGABLE GENOME		PHENOTHIAZINE	PHENOTHIAZINE
27035	NOX1	ION CHANNEL, ENZYME, TRANSPORTER, DRUGGABLE GENOME		TCMDC-125505	CHEMBL587104
27035	NOX1	ION CHANNEL, ENZYME, TRANSPORTER, DRUGGABLE GENOME	inhibitor	363894225
27035	NOX1	ION CHANNEL, ENZYME, TRANSPORTER, DRUGGABLE GENOME	inhibitor	363894227
27035	NOX1	ION CHANNEL, ENZYME, TRANSPORTER, DRUGGABLE GENOME	inhibitor	363894226

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