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: DUOXA1

Gene summary for DUOXA1

Gene summary.

Gene information	Species	Human
	Gene symbol	DUOXA1
	Gene ID	90527
	Gene name	dual oxidase maturation factor 1
	Gene Alias	NIP
	Cytomap	15q21.1
	Gene Type	protein-coding
	GO ID	GO:0006575
	UniProtAcc	A8K9Q6

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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
90527	DUOXA1	LZE4T	Human	Esophagus	ESCC	3.37e-04	1.60e-01	0.0811
90527	DUOXA1	LZE8T	Human	Esophagus	ESCC	3.81e-08	2.34e-01	0.067
90527	DUOXA1	LZE20T	Human	Esophagus	ESCC	2.00e-04	1.02e-01	0.0662
90527	DUOXA1	LZE24T	Human	Esophagus	ESCC	1.17e-20	2.30e-01	0.0596
90527	DUOXA1	P1T-E	Human	Esophagus	ESCC	3.46e-07	4.79e-01	0.0875
90527	DUOXA1	P2T-E	Human	Esophagus	ESCC	8.48e-11	1.17e-01	0.1177
90527	DUOXA1	P4T-E	Human	Esophagus	ESCC	4.40e-10	1.73e-01	0.1323
90527	DUOXA1	P5T-E	Human	Esophagus	ESCC	1.10e-12	3.14e-01	0.1327
90527	DUOXA1	P8T-E	Human	Esophagus	ESCC	1.23e-07	3.27e-02	0.0889
90527	DUOXA1	P9T-E	Human	Esophagus	ESCC	4.51e-09	2.28e-01	0.1131
90527	DUOXA1	P10T-E	Human	Esophagus	ESCC	7.73e-17	3.68e-01	0.116
90527	DUOXA1	P11T-E	Human	Esophagus	ESCC	1.01e-02	6.93e-02	0.1426
90527	DUOXA1	P12T-E	Human	Esophagus	ESCC	3.39e-11	2.41e-01	0.1122
90527	DUOXA1	P16T-E	Human	Esophagus	ESCC	4.07e-18	1.25e-01	0.1153
90527	DUOXA1	P20T-E	Human	Esophagus	ESCC	1.90e-12	2.46e-01	0.1124
90527	DUOXA1	P21T-E	Human	Esophagus	ESCC	5.15e-16	3.63e-01	0.1617
90527	DUOXA1	P22T-E	Human	Esophagus	ESCC	4.50e-15	1.20e-01	0.1236
90527	DUOXA1	P23T-E	Human	Esophagus	ESCC	1.24e-08	3.13e-01	0.108
90527	DUOXA1	P24T-E	Human	Esophagus	ESCC	9.39e-12	8.09e-02	0.1287
90527	DUOXA1	P26T-E	Human	Esophagus	ESCC	6.12e-17	1.54e-01	0.1276

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ
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:200037718	Esophagus	ESCC	regulation of reactive oxygen species metabolic process	100/8552	157/18723	3.87e-06	4.17e-05	100
GO:00065757	Esophagus	ESCC	cellular modified amino acid metabolic process	112/8552	188/18723	8.31e-05	6.06e-04	112
GO:007259318	Esophagus	ESCC	reactive oxygen species metabolic process	137/8552	239/18723	1.82e-04	1.16e-03	137
GO:00103101	Esophagus	ESCC	regulation of hydrogen peroxide metabolic process	16/8552	22/18723	9.46e-03	3.28e-02	16
GO:200037918	Esophagus	ESCC	positive regulation of reactive oxygen species metabolic process	45/8552	76/18723	1.21e-02	4.04e-02	45
GO:200037716	Oral cavity	OSCC	regulation of reactive oxygen species metabolic process	92/7305	157/18723	4.96e-07	7.27e-06	92
GO:007259316	Oral cavity	OSCC	reactive oxygen species metabolic process	122/7305	239/18723	9.73e-05	7.34e-04	122
GO:200037916	Oral cavity	OSCC	positive regulation of reactive oxygen species metabolic process	43/7305	76/18723	1.41e-03	6.84e-03	43
GO:00065756	Oral cavity	OSCC	cellular modified amino acid metabolic process	91/7305	188/18723	5.33e-03	2.07e-02	91
GO:200037717	Oral cavity	LP	regulation of reactive oxygen species metabolic process	67/4623	157/18723	5.54e-07	1.51e-05	67
GO:200037917	Oral cavity	LP	positive regulation of reactive oxygen species metabolic process	35/4623	76/18723	4.04e-05	5.90e-04	35
GO:007259317	Oral cavity	LP	reactive oxygen species metabolic process	85/4623	239/18723	1.04e-04	1.26e-03	85
GO:000657512	Oral cavity	LP	cellular modified amino acid metabolic process	64/4623	188/18723	2.43e-03	1.73e-02	64
GO:00065758	Skin	cSCC	cellular modified amino acid metabolic process	73/4864	188/18723	7.11e-05	6.85e-04	73
GO:200037719	Skin	cSCC	regulation of reactive oxygen species metabolic process	58/4864	157/18723	1.55e-03	9.60e-03	58
GO:007259319	Skin	cSCC	reactive oxygen species metabolic process	81/4864	239/18723	3.80e-03	2.03e-02	81
GO:00323502	Skin	cSCC	regulation of hormone metabolic process	16/4864	35/18723	9.09e-03	4.16e-02	16
GO:0072593110	Thyroid	PTC	reactive oxygen species metabolic process	108/5968	239/18723	1.02e-05	1.13e-04	108
GO:000657513	Thyroid	PTC	cellular modified amino acid metabolic process	85/5968	188/18723	8.29e-05	7.01e-04	85
GO:2000377110	Thyroid	PTC	regulation of reactive oxygen species metabolic process	71/5968	157/18723	3.03e-04	2.12e-03	71

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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

DUOXA1

SNV

Missense_Mutation

c.1222C>T

p.Arg408Trp

p.R408W

Q1HG43

protein_coding

deleterious_low_confidence(0.01)

benign(0.249)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

DUOXA1

deletion

Frame_Shift_Del

novel

c.140delN

p.Gly47GlufsTer12

p.G47Efs*12

Q1HG43

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

DUOXA1

SNV

Missense_Mutation

novel

c.1220C>A

p.Pro407Gln

p.P407Q

Q1HG43

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.694)

TCGA-FU-A2QG-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

DUOXA1

SNV

Missense_Mutation

c.128N>G

p.Pro43Arg

p.P43R

Q1HG43

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-JW-A5VG-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

DUOXA1

deletion

In_Frame_Del

novel

c.1014_1037delNNNNNNNNNNNNNNNNNNNNNNNN

p.Val339_Leu346del

p.V339_L346del

Q1HG43

protein_coding

TCGA-VS-A8EJ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

DUOXA1

SNV

Missense_Mutation

c.680C>T

p.Ala227Val

p.A227V

Q1HG43

protein_coding

tolerated(0.17)

benign(0.03)

TCGA-AA-3864-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

DUOXA1

SNV

Missense_Mutation

c.1379N>A

p.Arg460His

p.R460H

Q1HG43

protein_coding

deleterious_low_confidence(0)

benign(0.046)

TCGA-AA-3947-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

DUOXA1

SNV

Missense_Mutation

c.1379N>A

p.Arg460His

p.R460H

Q1HG43

protein_coding

deleterious_low_confidence(0)

benign(0.046)

TCGA-AD-6895-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Unknown

DUOXA1

SNV

Missense_Mutation

rs777729115

c.169N>A

p.Val57Met

p.V57M

Q1HG43

protein_coding

deleterious(0.01)

probably_damaging(0.992)

TCGA-AZ-6599-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

DUOXA1

SNV

Missense_Mutation

rs755140602

c.1328G>A

p.Gly443Asp

p.G443D

Q1HG43

protein_coding

deleterious_low_confidence(0)

benign(0)

TCGA-G4-6628-01

Colorectum

colon adenocarcinoma

Male

>=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

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