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: AZIN1

Gene summary for AZIN1

Gene summary.

Gene information	Species	Human
	Gene symbol	AZIN1
	Gene ID	51582
	Gene name	antizyme inhibitor 1
	Gene Alias	AZI
	Cytomap	8q22.3
	Gene Type	protein-coding
	GO ID	GO:0006082
	UniProtAcc	B3KTF6

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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
51582	AZIN1	LZE2D	Human	Esophagus	HGIN	1.42e-02	-1.80e-02	0.0642
51582	AZIN1	LZE4T	Human	Esophagus	ESCC	1.62e-27	1.18e+00	0.0811
51582	AZIN1	LZE5T	Human	Esophagus	ESCC	2.03e-02	2.77e-01	0.0514
51582	AZIN1	LZE7T	Human	Esophagus	ESCC	6.25e-07	3.78e-01	0.0667
51582	AZIN1	LZE8T	Human	Esophagus	ESCC	8.61e-11	4.85e-01	0.067
51582	AZIN1	LZE20T	Human	Esophagus	ESCC	2.23e-10	7.28e-01	0.0662
51582	AZIN1	LZE22D1	Human	Esophagus	HGIN	2.93e-03	-3.64e-02	0.0595
51582	AZIN1	LZE22T	Human	Esophagus	ESCC	5.45e-07	5.51e-01	0.068
51582	AZIN1	LZE24T	Human	Esophagus	ESCC	6.51e-32	1.26e+00	0.0596
51582	AZIN1	LZE21T	Human	Esophagus	ESCC	4.17e-03	7.36e-01	0.0655
51582	AZIN1	P1T-E	Human	Esophagus	ESCC	9.28e-06	6.25e-01	0.0875
51582	AZIN1	P2T-E	Human	Esophagus	ESCC	5.31e-52	9.78e-01	0.1177
51582	AZIN1	P4T-E	Human	Esophagus	ESCC	2.09e-38	9.73e-01	0.1323
51582	AZIN1	P5T-E	Human	Esophagus	ESCC	5.29e-42	9.89e-01	0.1327
51582	AZIN1	P8T-E	Human	Esophagus	ESCC	7.30e-27	6.80e-01	0.0889
51582	AZIN1	P9T-E	Human	Esophagus	ESCC	4.07e-14	4.08e-01	0.1131
51582	AZIN1	P10T-E	Human	Esophagus	ESCC	1.72e-15	4.99e-01	0.116
51582	AZIN1	P11T-E	Human	Esophagus	ESCC	5.30e-17	1.11e+00	0.1426
51582	AZIN1	P12T-E	Human	Esophagus	ESCC	3.44e-50	1.35e+00	0.1122
51582	AZIN1	P15T-E	Human	Esophagus	ESCC	4.70e-36	9.75e-01	0.1149

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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
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
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:004217627	Esophagus	HGIN	regulation of protein catabolic process	119/2587	391/18723	8.09e-18	2.43e-15	119
GO:000989520	Esophagus	HGIN	negative regulation of catabolic process	87/2587	320/18723	1.74e-10	1.68e-08	87
GO:004217720	Esophagus	HGIN	negative regulation of protein catabolic process	37/2587	121/18723	1.47e-06	5.56e-05	37
GO:0042176111	Esophagus	ESCC	regulation of protein catabolic process	280/8552	391/18723	8.65e-26	2.39e-23	280
GO:0009895111	Esophagus	ESCC	negative regulation of catabolic process	201/8552	320/18723	3.88e-10	1.05e-08	201
GO:0042177111	Esophagus	ESCC	negative regulation of protein catabolic process	84/8552	121/18723	1.03e-07	1.69e-06	84
GO:004217612	Liver	Cirrhotic	regulation of protein catabolic process	181/4634	391/18723	7.94e-21	2.77e-18	181
GO:19016051	Liver	Cirrhotic	alpha-amino acid metabolic process	82/4634	195/18723	7.72e-08	2.30e-06	82
GO:000989512	Liver	Cirrhotic	negative regulation of catabolic process	121/4634	320/18723	1.21e-07	3.39e-06	121
GO:000652011	Liver	Cirrhotic	cellular amino acid metabolic process	103/4634	284/18723	8.88e-06	1.30e-04	103
GO:004217712	Liver	Cirrhotic	negative regulation of protein catabolic process	51/4634	121/18723	1.93e-05	2.57e-04	51
GO:0006595	Liver	Cirrhotic	polyamine metabolic process	12/4634	18/18723	2.07e-04	1.90e-03	12
GO:00065962	Liver	Cirrhotic	polyamine biosynthetic process	10/4634	14/18723	3.11e-04	2.72e-03	10
GO:0044106	Liver	Cirrhotic	cellular amine metabolic process	43/4634	113/18723	1.15e-03	7.83e-03	43
GO:0006576	Liver	Cirrhotic	cellular biogenic amine metabolic process	38/4634	101/18723	2.72e-03	1.59e-02	38
GO:0009308	Liver	Cirrhotic	amine metabolic process	43/4634	118/18723	3.03e-03	1.72e-02	43
GO:004217622	Liver	HCC	regulation of protein catabolic process	267/7958	391/18723	2.45e-25	7.38e-23	267
GO:000989522	Liver	HCC	negative regulation of catabolic process	196/7958	320/18723	7.98e-12	3.35e-10	196
GO:19016052	Liver	HCC	alpha-amino acid metabolic process	124/7958	195/18723	2.07e-09	5.79e-08	124
GO:00065202	Liver	HCC	cellular amino acid metabolic process	167/7958	284/18723	1.91e-08	4.56e-07	167

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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

AZIN1

SNV

Missense_Mutation

rs779160903

c.916N>A

p.Gly306Arg

p.G306R

O14977

protein_coding

tolerated(0.21)

benign(0.007)

TCGA-A2-A0ER-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

AZIN1

SNV

Missense_Mutation

c.827N>G

p.Tyr276Cys

p.Y276C

O14977

protein_coding

deleterious(0)

probably_damaging(0.987)

TCGA-A8-A06O-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

letrozole

AZIN1

SNV

Missense_Mutation

c.371C>T

p.Ala124Val

p.A124V

O14977

protein_coding

deleterious(0)

probably_damaging(0.993)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

AZIN1

SNV

Missense_Mutation

c.1189N>A

p.Asp397Asn

p.D397N

O14977

protein_coding

tolerated(0.05)

possibly_damaging(0.698)

TCGA-D8-A140-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin+cyclophosphamid

AZIN1

SNV

Missense_Mutation

c.784N>A

p.Glu262Lys

p.E262K

O14977

protein_coding

tolerated(0.32)

benign(0.049)

TCGA-EK-A2H0-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

AZIN1

SNV

Missense_Mutation

c.461N>G

p.His154Arg

p.H154R

O14977

protein_coding

tolerated(0.68)

benign(0.007)

TCGA-MY-A5BD-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

AZIN1

SNV

Missense_Mutation

c.589C>T

p.His197Tyr

p.H197Y

O14977

protein_coding

deleterious(0)

probably_damaging(0.988)

TCGA-Q1-A73O-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

AZIN1

SNV

Missense_Mutation

c.784N>A

p.Glu262Lys

p.E262K

O14977

protein_coding

tolerated(0.32)

benign(0.049)

TCGA-ZJ-A8QQ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

AZIN1

SNV

Missense_Mutation

c.937N>G

p.Met313Val

p.M313V

O14977

protein_coding

tolerated(0.92)

benign(0.003)

TCGA-AA-3663-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

AZIN1

SNV

Missense_Mutation

c.748N>A

p.His250Asn

p.H250N

O14977

protein_coding

tolerated(0.13)

benign(0)

TCGA-AA-3977-01

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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