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: OAZ2

Gene summary for OAZ2

Gene summary.

Gene information	Species	Human
	Gene symbol	OAZ2
	Gene ID	4947
	Gene name	ornithine decarboxylase antizyme 2
	Gene Alias	AZ2
	Cytomap	15q22.31
	Gene Type	protein-coding
	GO ID	GO:0006576
	UniProtAcc	O95190

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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
4947	OAZ2	P48T-E	Human	Esophagus	ESCC	4.84e-10	2.55e-01	0.0959
4947	OAZ2	P49T-E	Human	Esophagus	ESCC	4.58e-15	1.19e+00	0.1768
4947	OAZ2	P52T-E	Human	Esophagus	ESCC	7.91e-18	4.89e-01	0.1555
4947	OAZ2	P54T-E	Human	Esophagus	ESCC	4.94e-09	1.23e-01	0.0975
4947	OAZ2	P56T-E	Human	Esophagus	ESCC	4.04e-12	1.12e+00	0.1613
4947	OAZ2	P57T-E	Human	Esophagus	ESCC	3.27e-20	3.66e-01	0.0926
4947	OAZ2	P61T-E	Human	Esophagus	ESCC	1.14e-16	3.94e-01	0.099
4947	OAZ2	P62T-E	Human	Esophagus	ESCC	3.33e-23	1.97e-01	0.1302
4947	OAZ2	P65T-E	Human	Esophagus	ESCC	1.79e-19	2.65e-01	0.0978
4947	OAZ2	P74T-E	Human	Esophagus	ESCC	6.78e-24	6.88e-01	0.1479
4947	OAZ2	P75T-E	Human	Esophagus	ESCC	5.12e-14	4.02e-01	0.1125
4947	OAZ2	P76T-E	Human	Esophagus	ESCC	4.90e-22	4.84e-01	0.1207
4947	OAZ2	P79T-E	Human	Esophagus	ESCC	1.01e-19	4.73e-01	0.1154
4947	OAZ2	P80T-E	Human	Esophagus	ESCC	2.00e-19	3.73e-01	0.155
4947	OAZ2	P82T-E	Human	Esophagus	ESCC	4.85e-08	3.16e-01	0.1072
4947	OAZ2	P83T-E	Human	Esophagus	ESCC	3.30e-24	4.97e-01	0.1738
4947	OAZ2	P84T-E	Human	Esophagus	ESCC	7.74e-04	9.76e-02	0.0933
4947	OAZ2	P89T-E	Human	Esophagus	ESCC	6.75e-12	6.37e-01	0.1752
4947	OAZ2	P91T-E	Human	Esophagus	ESCC	1.07e-11	1.09e+00	0.1828
4947	OAZ2	P107T-E	Human	Esophagus	ESCC	1.68e-22	6.03e-01	0.171

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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
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
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:0042176	Colorectum	AD	regulation of protein catabolic process	160/3918	391/18723	1.06e-19	7.34e-17	160
GO:0009896	Colorectum	AD	positive regulation of catabolic process	180/3918	492/18723	4.33e-16	1.94e-13	180
GO:0045732	Colorectum	AD	positive regulation of protein catabolic process	92/3918	231/18723	3.85e-11	4.47e-09	92
GO:1904951	Colorectum	AD	positive regulation of establishment of protein localization	112/3918	319/18723	2.55e-09	1.80e-07	112
GO:0051222	Colorectum	AD	positive regulation of protein transport	106/3918	303/18723	8.45e-09	5.08e-07	106
GO:0090316	Colorectum	AD	positive regulation of intracellular protein transport	62/3918	160/18723	1.82e-07	7.79e-06	62
GO:0032388	Colorectum	AD	positive regulation of intracellular transport	74/3918	202/18723	1.83e-07	7.80e-06	74
GO:0032386	Colorectum	AD	regulation of intracellular transport	109/3918	337/18723	5.33e-07	1.95e-05	109
GO:0033157	Colorectum	AD	regulation of intracellular protein transport	80/3918	229/18723	5.81e-07	2.09e-05	80
GO:00421761	Colorectum	SER	regulation of protein catabolic process	126/2897	391/18723	5.33e-17	2.52e-14	126
GO:00457321	Colorectum	SER	positive regulation of protein catabolic process	77/2897	231/18723	9.91e-12	1.90e-09	77
GO:00098961	Colorectum	SER	positive regulation of catabolic process	132/2897	492/18723	4.16e-11	6.72e-09	132
GO:19049511	Colorectum	SER	positive regulation of establishment of protein localization	91/2897	319/18723	1.69e-09	1.68e-07	91
GO:00512221	Colorectum	SER	positive regulation of protein transport	85/2897	303/18723	1.36e-08	1.05e-06	85
GO:00331571	Colorectum	SER	regulation of intracellular protein transport	68/2897	229/18723	3.41e-08	2.30e-06	68
GO:00903161	Colorectum	SER	positive regulation of intracellular protein transport	52/2897	160/18723	5.64e-08	3.72e-06	52
GO:00323861	Colorectum	SER	regulation of intracellular transport	89/2897	337/18723	1.34e-07	7.96e-06	89
GO:00323881	Colorectum	SER	positive regulation of intracellular transport	59/2897	202/18723	4.98e-07	2.48e-05	59
GO:0051051	Colorectum	SER	negative regulation of transport	98/2897	470/18723	1.01e-03	1.19e-02	98
GO:00421762	Colorectum	MSS	regulation of protein catabolic process	145/3467	391/18723	2.03e-18	1.17e-15	145

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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

OAZ2

SNV

Missense_Mutation

c.18N>A

p.Asp6Glu

p.D6E

O95190

protein_coding

tolerated(1)

benign(0.417)

TCGA-A8-A07G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

5-fluorouracil

OAZ2

deletion

Frame_Shift_Del

novel

c.77delN

p.Pro26GlnfsTer31

p.P26Qfs*31

O95190

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

OAZ2

SNV

Missense_Mutation

c.521N>C

p.Val174Ala

p.V174A

O95190

protein_coding

tolerated(0.64)

benign(0.018)

TCGA-AY-6197-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

OAZ2

SNV

Missense_Mutation

rs369960638

c.181N>A

p.Glu61Lys

p.E61K

O95190

protein_coding

tolerated(0.48)

benign(0.163)

TCGA-AJ-A3BH-01

Endometrium

uterine corpus endometrioid carcinoma

Female

Unknown

I/II

Unknown

OAZ2

SNV

Missense_Mutation

novel

c.223N>C

p.Lys75Gln

p.K75Q

O95190

protein_coding

tolerated(0.07)

benign(0.037)

TCGA-AJ-A3EL-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

OAZ2

SNV

Missense_Mutation

novel

c.202G>T

p.Asp68Tyr

p.D68Y

O95190

protein_coding

deleterious(0.01)

possibly_damaging(0.907)

TCGA-AJ-A5DW-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

OAZ2

SNV

Missense_Mutation

novel

c.419N>A

p.Arg140Lys

p.R140K

O95190

protein_coding

tolerated(0.27)

benign(0.246)

TCGA-AP-A1DK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

OAZ2

SNV

Missense_Mutation

novel

c.549G>T

p.Gln183His

p.Q183H

O95190

protein_coding

deleterious(0)

benign(0.059)

TCGA-AX-A2HC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

OAZ2

SNV

Missense_Mutation

novel

c.27N>G

p.Ile9Met

p.I9M

O95190

protein_coding

tolerated(0.13)

benign(0.374)

TCGA-DF-A2KN-01

Endometrium

uterine corpus endometrioid carcinoma

Female

Unknown

I/II

Unknown

OAZ2

SNV

Missense_Mutation

novel

c.296G>T

p.Ser99Ile

p.S99I

O95190

protein_coding

deleterious(0.01)

benign(0.14)

TCGA-DF-A2KU-01

Endometrium

uterine corpus endometrioid carcinoma

Female

Unknown

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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