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: DAZAP1

Gene summary for DAZAP1

Gene summary.

Gene information	Species	Human
	Gene symbol	DAZAP1
	Gene ID	26528
	Gene name	DAZ associated protein 1
	Gene Alias	DAZAP1
	Cytomap	19p13.3
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	A0A0S2Z569

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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
26528	DAZAP1	HTA11_3410_2000001011	Human	Colorectum	AD	2.83e-02	6.47e-02	0.0155
26528	DAZAP1	HTA11_347_2000001011	Human	Colorectum	AD	2.06e-06	3.00e-01	-0.1954
26528	DAZAP1	HTA11_1391_2000001011	Human	Colorectum	AD	2.60e-05	4.79e-01	-0.059
26528	DAZAP1	HTA11_7862_2000001011	Human	Colorectum	AD	2.65e-02	3.91e-01	-0.0179
26528	DAZAP1	HTA11_99999970781_79442	Human	Colorectum	MSS	1.75e-05	4.30e-01	0.294
26528	DAZAP1	HTA11_99999971662_82457	Human	Colorectum	MSS	2.75e-12	6.77e-01	0.3859
26528	DAZAP1	A015-C-203	Human	Colorectum	FAP	6.94e-06	2.58e-02	-0.1294
26528	DAZAP1	A002-C-205	Human	Colorectum	FAP	8.56e-04	-2.23e-01	-0.1236
26528	DAZAP1	A015-C-106	Human	Colorectum	FAP	2.60e-02	2.11e-02	-0.0511
26528	DAZAP1	A015-C-104	Human	Colorectum	FAP	9.06e-07	-2.73e-02	-0.1899
26528	DAZAP1	A002-C-016	Human	Colorectum	FAP	2.32e-04	-8.14e-02	0.0521
26528	DAZAP1	A002-C-116	Human	Colorectum	FAP	1.34e-09	-2.11e-01	-0.0452
26528	DAZAP1	F034	Human	Colorectum	FAP	1.93e-04	-1.03e-01	-0.0665
26528	DAZAP1	LZE2T	Human	Esophagus	ESCC	3.40e-05	4.46e-01	0.082
26528	DAZAP1	LZE4T	Human	Esophagus	ESCC	4.47e-04	-9.87e-03	0.0811
26528	DAZAP1	LZE5T	Human	Esophagus	ESCC	1.79e-03	1.46e-01	0.0514
26528	DAZAP1	LZE7T	Human	Esophagus	ESCC	1.70e-06	3.44e-01	0.0667
26528	DAZAP1	LZE20T	Human	Esophagus	ESCC	1.92e-08	6.76e-02	0.0662
26528	DAZAP1	LZE22D1	Human	Esophagus	HGIN	1.15e-04	5.74e-02	0.0595
26528	DAZAP1	LZE22T	Human	Esophagus	ESCC	5.10e-07	2.79e-01	0.068

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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:0008380	Colorectum	AD	RNA splicing	169/3918	434/18723	3.59e-18	2.04e-15	169
GO:0000377	Colorectum	AD	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	130/3918	320/18723	5.88e-16	2.16e-13	130
GO:0000398	Colorectum	AD	mRNA splicing, via spliceosome	130/3918	320/18723	5.88e-16	2.16e-13	130
GO:0000375	Colorectum	AD	RNA splicing, via transesterification reactions	131/3918	324/18723	7.11e-16	2.22e-13	131
GO:1903311	Colorectum	AD	regulation of mRNA metabolic process	117/3918	288/18723	1.69e-14	4.23e-12	117
GO:0043484	Colorectum	AD	regulation of RNA splicing	70/3918	148/18723	6.47e-13	1.16e-10	70
GO:0048024	Colorectum	AD	regulation of mRNA splicing, via spliceosome	50/3918	101/18723	1.62e-10	1.56e-08	50
GO:0050684	Colorectum	AD	regulation of mRNA processing	61/3918	137/18723	4.23e-10	3.58e-08	61
GO:1903313	Colorectum	AD	positive regulation of mRNA metabolic process	44/3918	118/18723	3.20e-05	5.87e-04	44
GO:0001890	Colorectum	AD	placenta development	51/3918	144/18723	3.99e-05	7.16e-04	51
GO:0033120	Colorectum	AD	positive regulation of RNA splicing	19/3918	37/18723	4.08e-05	7.26e-04	19
GO:0048026	Colorectum	AD	positive regulation of mRNA splicing, via spliceosome	12/3918	22/18723	5.38e-04	5.74e-03	12
GO:0061458	Colorectum	AD	reproductive system development	116/3918	427/18723	1.11e-03	1.01e-02	116
GO:0048608	Colorectum	AD	reproductive structure development	114/3918	424/18723	1.78e-03	1.47e-02	114
GO:00083802	Colorectum	MSS	RNA splicing	159/3467	434/18723	1.75e-19	1.22e-16	159
GO:19033112	Colorectum	MSS	regulation of mRNA metabolic process	115/3467	288/18723	1.23e-17	6.41e-15	115
GO:00003772	Colorectum	MSS	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	121/3467	320/18723	2.52e-16	8.27e-14	121
GO:00003982	Colorectum	MSS	mRNA splicing, via spliceosome	121/3467	320/18723	2.52e-16	8.27e-14	121
GO:00003752	Colorectum	MSS	RNA splicing, via transesterification reactions	122/3467	324/18723	2.75e-16	8.58e-14	122
GO:00434842	Colorectum	MSS	regulation of RNA splicing	66/3467	148/18723	2.44e-13	5.25e-11	66

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa030152	Colorectum	FAP	mRNA surveillance pathway	26/1404	97/8465	7.11e-03	2.64e-02	1.60e-02	26
hsa030153	Colorectum	FAP	mRNA surveillance pathway	26/1404	97/8465	7.11e-03	2.64e-02	1.60e-02	26
hsa030159	Esophagus	HGIN	mRNA surveillance pathway	30/1383	97/8465	2.48e-04	2.69e-03	2.14e-03	30
hsa0301514	Esophagus	HGIN	mRNA surveillance pathway	30/1383	97/8465	2.48e-04	2.69e-03	2.14e-03	30
hsa0301524	Esophagus	ESCC	mRNA surveillance pathway	72/4205	97/8465	6.12e-07	4.10e-06	2.10e-06	72
hsa0301534	Esophagus	ESCC	mRNA surveillance pathway	72/4205	97/8465	6.12e-07	4.10e-06	2.10e-06	72
hsa030154	Liver	Cirrhotic	mRNA surveillance pathway	46/2530	97/8465	1.92e-04	1.30e-03	8.03e-04	46
hsa0301511	Liver	Cirrhotic	mRNA surveillance pathway	46/2530	97/8465	1.92e-04	1.30e-03	8.03e-04	46
hsa0301521	Liver	HCC	mRNA surveillance pathway	66/4020	97/8465	3.16e-05	1.88e-04	1.04e-04	66
hsa0301531	Liver	HCC	mRNA surveillance pathway	66/4020	97/8465	3.16e-05	1.88e-04	1.04e-04	66
hsa030158	Oral cavity	OSCC	mRNA surveillance pathway	75/3704	97/8465	1.30e-11	2.01e-10	1.02e-10	75
hsa0301513	Oral cavity	OSCC	mRNA surveillance pathway	75/3704	97/8465	1.30e-11	2.01e-10	1.02e-10	75
hsa0301523	Oral cavity	LP	mRNA surveillance pathway	50/2418	97/8465	1.39e-06	1.50e-05	9.66e-06	50
hsa0301533	Oral cavity	LP	mRNA surveillance pathway	50/2418	97/8465	1.39e-06	1.50e-05	9.66e-06	50

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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

DAZAP1

SNV

Missense_Mutation

rs770991534

c.320N>A

p.Ser107Asn

p.S107N

Q96EP5

protein_coding

tolerated(0.28)

benign(0.009)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DAZAP1

insertion

Frame_Shift_Ins

novel

c.801_802insACAGCTGGTGGACACGGCGCCAACC

p.Ser268ThrfsTer167

p.S268Tfs*167

Q96EP5

protein_coding

TCGA-A8-A097-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

DAZAP1

insertion

Nonsense_Mutation

novel

c.208_209insTCTAAGGCGAGCGCTGTCTTGATCCTGAATGTTTTCTCATTGAATC

p.Ser70IlefsTer2

p.S70Ifs*2

Q96EP5

protein_coding

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

DAZAP1

deletion

Frame_Shift_Del

c.764delN

p.Pro257ArgfsTer78

p.P257Rfs*78

Q96EP5

protein_coding

TCGA-BH-A0HA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

DAZAP1

deletion

Frame_Shift_Del

c.764delN

p.Pro257ArgfsTer78

p.P257Rfs*78

Q96EP5

protein_coding

TCGA-E2-A154-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

DAZAP1

SNV

Missense_Mutation

rs771366198

c.853N>A

p.Gly285Ser

p.G285S

Q96EP5

protein_coding

tolerated(0.24)

benign(0.001)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

DAZAP1

SNV

Missense_Mutation

novel

c.352N>A

p.Gly118Ser

p.G118S

Q96EP5

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-C5-A8XK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

DAZAP1

SNV

Missense_Mutation

rs771366198

c.853N>A

p.Gly285Ser

p.G285S

Q96EP5

protein_coding

tolerated(0.24)

benign(0.001)

TCGA-EK-A2RJ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

DAZAP1

SNV

Missense_Mutation

novel

c.57N>T

p.Trp19Cys

p.W19C

Q96EP5

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-VS-A9UY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

DAZAP1

SNV

Missense_Mutation

c.920C>T

p.Pro307Leu

p.P307L

Q96EP5

protein_coding

deleterious(0.03)

benign(0.06)

TCGA-DM-A0X9-01

Colorectum

colon adenocarcinoma

Female

>=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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