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: OXR1

Gene summary for OXR1

Gene summary.

Gene information	Species	Human
	Gene symbol	OXR1
	Gene ID	55074
	Gene name	oxidation resistance 1
	Gene Alias	CHEGDD
	Cytomap	8q23.1
	Gene Type	protein-coding
	GO ID	GO:0006464
	UniProtAcc	Q8N573

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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
55074	OXR1	CA_HPV_3	Human	Cervix	CC	1.09e-03	9.66e-02	0.0414
55074	OXR1	CCI_1	Human	Cervix	CC	5.66e-04	7.60e-01	0.528
55074	OXR1	CCI_2	Human	Cervix	CC	9.61e-05	1.36e+00	0.5249
55074	OXR1	CCI_3	Human	Cervix	CC	2.05e-04	5.72e-01	0.516
55074	OXR1	HTA11_3410_2000001011	Human	Colorectum	AD	2.68e-20	-6.50e-01	0.0155
55074	OXR1	HTA11_2951_2000001011	Human	Colorectum	AD	8.57e-03	-7.23e-01	0.0216
55074	OXR1	HTA11_866_2000001011	Human	Colorectum	AD	8.96e-07	-2.91e-01	-0.1001
55074	OXR1	HTA11_866_3004761011	Human	Colorectum	AD	4.61e-06	-4.77e-01	0.096
55074	OXR1	HTA11_8622_2000001021	Human	Colorectum	SER	1.09e-03	-6.10e-01	0.0528
55074	OXR1	HTA11_7696_3000711011	Human	Colorectum	AD	8.00e-08	-3.59e-01	0.0674
55074	OXR1	HTA11_6818_2000001011	Human	Colorectum	AD	8.25e-04	-3.97e-01	0.0112
55074	OXR1	HTA11_6818_2000001021	Human	Colorectum	AD	3.27e-08	-5.92e-01	0.0588
55074	OXR1	HTA11_99999973899_84307	Human	Colorectum	MSS	1.99e-03	-4.91e-01	0.2585
55074	OXR1	HTA11_99999974143_84620	Human	Colorectum	MSS	8.73e-22	-6.05e-01	0.3005
55074	OXR1	F007	Human	Colorectum	FAP	1.04e-05	-3.59e-01	0.1176
55074	OXR1	A002-C-010	Human	Colorectum	FAP	3.11e-04	-2.28e-01	0.242
55074	OXR1	A001-C-207	Human	Colorectum	FAP	1.01e-06	-3.23e-01	0.1278
55074	OXR1	A015-C-203	Human	Colorectum	FAP	1.91e-40	-5.46e-01	-0.1294
55074	OXR1	A015-C-204	Human	Colorectum	FAP	7.77e-12	-4.53e-01	-0.0228
55074	OXR1	A014-C-040	Human	Colorectum	FAP	1.31e-08	-6.05e-01	-0.1184

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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
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:19032017	Liver	Cirrhotic	regulation of oxidative stress-induced cell death	33/4634	74/18723	1.51e-04	1.45e-03	33
GO:00364755	Liver	Cirrhotic	neuron death in response to oxidative stress	17/4634	31/18723	3.19e-04	2.77e-03	17
GO:19004077	Liver	Cirrhotic	regulation of cellular response to oxidative stress	36/4634	89/18723	7.79e-04	5.73e-03	36
GO:00435242	Liver	Cirrhotic	negative regulation of neuron apoptotic process	51/4634	145/18723	3.15e-03	1.78e-02	51
GO:19032027	Liver	Cirrhotic	negative regulation of oxidative stress-induced cell death	22/4634	53/18723	5.36e-03	2.73e-02	22
GO:19028827	Liver	Cirrhotic	regulation of response to oxidative stress	36/4634	98/18723	5.44e-03	2.77e-02	36
GO:19032035	Liver	Cirrhotic	regulation of oxidative stress-induced neuron death	13/4634	27/18723	7.07e-03	3.41e-02	13
GO:19032046	Liver	Cirrhotic	negative regulation of oxidative stress-induced neuron death	10/4634	19/18723	8.23e-03	3.83e-02	10
GO:000697922	Liver	HCC	response to oxidative stress	281/7958	446/18723	9.75e-19	1.24e-16	281
GO:006219722	Liver	HCC	cellular response to chemical stress	216/7958	337/18723	6.86e-16	5.44e-14	216
GO:003459922	Liver	HCC	cellular response to oxidative stress	183/7958	288/18723	3.65e-13	1.93e-11	183
GO:007099722	Liver	HCC	neuron death	202/7958	361/18723	1.44e-07	2.70e-06	202
GO:190121412	Liver	HCC	regulation of neuron death	179/7958	319/18723	5.65e-07	9.01e-06	179
GO:005140212	Liver	HCC	neuron apoptotic process	135/7958	246/18723	5.64e-05	5.26e-04	135
GO:004352312	Liver	HCC	regulation of neuron apoptotic process	117/7958	212/18723	1.25e-04	1.03e-03	117
GO:190121512	Liver	HCC	negative regulation of neuron death	113/7958	208/18723	3.68e-04	2.54e-03	113
GO:003647511	Liver	HCC	neuron death in response to oxidative stress	22/7958	31/18723	1.27e-03	6.92e-03	22
GO:003647312	Liver	HCC	cell death in response to oxidative stress	55/7958	95/18723	1.76e-03	9.12e-03	55
GO:190288212	Liver	HCC	regulation of response to oxidative stress	55/7958	98/18723	4.46e-03	1.93e-02	55
GO:190040712	Liver	HCC	regulation of cellular response to oxidative stress	50/7958	89/18723	6.33e-03	2.58e-02	50

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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

OXR1

SNV

Missense_Mutation

novel

c.819N>A

p.Met273Ile

p.M273I

Q8N573

protein_coding

tolerated(0.12)

benign(0.068)

TCGA-A2-A4S3-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

OXR1

SNV

Missense_Mutation

rs528049194

c.1985G>A

p.Arg662His

p.R662H

Q8N573

protein_coding

deleterious(0.01)

benign(0.07)

TCGA-AC-A62V-01

Breast

breast invasive carcinoma

Male

<65

III/IV

Targeted Molecular therapy

denosumab

OXR1

SNV

Missense_Mutation

rs140427774

c.364N>A

p.Glu122Lys

p.E122K

Q8N573

protein_coding

tolerated(0.74)

possibly_damaging(0.904)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

OXR1

SNV

Missense_Mutation

c.1368N>T

p.Glu456Asp

p.E456D

Q8N573

protein_coding

tolerated(0.42)

benign(0.003)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

OXR1

SNV

Missense_Mutation

novel

c.1859N>A

p.Gly620Asp

p.G620D

Q8N573

protein_coding

deleterious(0.04)

probably_damaging(0.965)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

OXR1

SNV

Missense_Mutation

novel

c.2063N>G

p.Asn688Ser

p.N688S

Q8N573

protein_coding

tolerated(0.13)

benign(0.043)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

OXR1

SNV

Missense_Mutation

c.1958N>T

p.Glu653Val

p.E653V

Q8N573

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AO-A0J5-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Other, specify in notesBisphosphonate

zoledronic

OXR1

SNV

Missense_Mutation

rs149485264

c.584N>A

p.Arg195Gln

p.R195Q

Q8N573

protein_coding

tolerated(0.11)

possibly_damaging(0.856)

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

OXR1

SNV

Missense_Mutation

c.479T>G

p.Val160Gly

p.V160G

Q8N573

protein_coding

tolerated(0.27)

benign(0.063)

TCGA-AQ-A04H-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

taxotere

OXR1

SNV

Missense_Mutation

c.913A>C

p.Thr305Pro

p.T305P

Q8N573

protein_coding

tolerated(0.34)

benign(0.001)

TCGA-AQ-A04J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

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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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