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:000697913	Lung	AIS	response to oxidative stress	75/1849	446/18723	2.97e-06	1.60e-04	75
GO:006219713	Lung	AIS	cellular response to chemical stress	58/1849	337/18723	1.91e-05	6.62e-04	58
GO:003459913	Lung	AIS	cellular response to oxidative stress	49/1849	288/18723	1.10e-04	2.57e-03	49
GO:007099713	Lung	AIS	neuron death	58/1849	361/18723	1.39e-04	3.05e-03	58
GO:190288213	Lung	AIS	regulation of response to oxidative stress	22/1849	98/18723	1.84e-04	3.83e-03	22
GO:190320113	Lung	AIS	regulation of oxidative stress-induced cell death	18/1849	74/18723	2.42e-04	4.78e-03	18
GO:190040713	Lung	AIS	regulation of cellular response to oxidative stress	20/1849	89/18723	3.50e-04	6.28e-03	20
GO:003647512	Lung	AIS	neuron death in response to oxidative stress	10/1849	31/18723	5.46e-04	8.65e-03	10
GO:190121413	Lung	AIS	regulation of neuron death	50/1849	319/18723	6.90e-04	1.02e-02	50
GO:190320312	Lung	AIS	regulation of oxidative stress-induced neuron death	9/1849	27/18723	7.88e-04	1.11e-02	9
GO:003647313	Lung	AIS	cell death in response to oxidative stress	20/1849	95/18723	8.52e-04	1.17e-02	20
GO:0007626	Lung	AIS	locomotory behavior	31/1849	179/18723	1.39e-03	1.70e-02	31
GO:20001691	Lung	AIS	regulation of peptidyl-cysteine S-nitrosylation	5/1849	10/18723	1.54e-03	1.82e-02	5
GO:190320411	Lung	AIS	negative regulation of oxidative stress-induced neuron death	7/1849	19/18723	1.57e-03	1.83e-02	7
GO:190320212	Lung	AIS	negative regulation of oxidative stress-induced cell death	13/1849	53/18723	1.57e-03	1.83e-02	13
GO:001701411	Lung	AIS	protein nitrosylation	6/1849	16/18723	3.08e-03	2.98e-02	6
GO:001811911	Lung	AIS	peptidyl-cysteine S-nitrosylation	6/1849	16/18723	3.08e-03	2.98e-02	6
GO:19028831	Lung	AIS	negative regulation of response to oxidative stress	8/1849	27/18723	3.56e-03	3.35e-02	8
GO:000697923	Lung	MIAC	response to oxidative stress	43/967	446/18723	6.39e-05	3.12e-03	43
GO:006219723	Lung	MIAC	cellular response to chemical stress	34/967	337/18723	1.54e-04	6.04e-03	34

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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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