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: DAZAP2

Gene summary for DAZAP2

Gene summary.

Gene information	Species	Human
	Gene symbol	DAZAP2
	Gene ID	9802
	Gene name	DAZ associated protein 2
	Gene Alias	PRTB
	Cytomap	12q13.13
	Gene Type	protein-coding
	GO ID	GO:0001932
	UniProtAcc	Q15038

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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
9802	DAZAP2	Pt13.a	Human	Liver	HCC	3.41e-04	2.55e-03	0.021
9802	DAZAP2	Pt13.b	Human	Liver	HCC	1.26e-32	2.52e-02	0.0251
9802	DAZAP2	Pt14.a	Human	Liver	HCC	2.83e-08	8.30e-02	0.0169
9802	DAZAP2	Pt14.b	Human	Liver	HCC	1.32e-11	2.25e-01	0.018
9802	DAZAP2	S014	Human	Liver	HCC	1.14e-26	1.69e+00	0.2254
9802	DAZAP2	S015	Human	Liver	HCC	5.85e-23	1.74e+00	0.2375
9802	DAZAP2	S016	Human	Liver	HCC	8.00e-31	1.63e+00	0.2243
9802	DAZAP2	S027	Human	Liver	HCC	4.41e-08	1.36e+00	0.2446
9802	DAZAP2	S028	Human	Liver	HCC	6.07e-19	1.43e+00	0.2503
9802	DAZAP2	S029	Human	Liver	HCC	3.31e-22	1.84e+00	0.2581
9802	DAZAP2	C04	Human	Oral cavity	OSCC	9.20e-39	2.12e+00	0.2633
9802	DAZAP2	C21	Human	Oral cavity	OSCC	2.50e-70	2.30e+00	0.2678
9802	DAZAP2	C30	Human	Oral cavity	OSCC	9.11e-58	3.08e+00	0.3055
9802	DAZAP2	C38	Human	Oral cavity	OSCC	7.58e-23	2.19e+00	0.172
9802	DAZAP2	C43	Human	Oral cavity	OSCC	6.33e-44	9.05e-01	0.1704
9802	DAZAP2	C46	Human	Oral cavity	OSCC	2.85e-70	1.46e+00	0.1673
9802	DAZAP2	C51	Human	Oral cavity	OSCC	1.26e-30	1.52e+00	0.2674
9802	DAZAP2	C57	Human	Oral cavity	OSCC	9.18e-62	1.56e+00	0.1679
9802	DAZAP2	C06	Human	Oral cavity	OSCC	6.36e-14	2.02e+00	0.2699
9802	DAZAP2	C07	Human	Oral cavity	OSCC	1.60e-09	1.66e+00	0.2491

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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
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
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:0033674	Colorectum	AD	positive regulation of kinase activity	131/3918	467/18723	1.28e-04	1.85e-03	131
GO:0045860	Colorectum	AD	positive regulation of protein kinase activity	107/3918	386/18723	8.01e-04	7.92e-03	107
GO:0071900	Colorectum	AD	regulation of protein serine/threonine kinase activity	98/3918	359/18723	2.18e-03	1.73e-02	98
GO:0071902	Colorectum	AD	positive regulation of protein serine/threonine kinase activity	58/3918	200/18723	4.09e-03	2.84e-02	58
GO:00336741	Colorectum	SER	positive regulation of kinase activity	95/2897	467/18723	2.62e-03	2.41e-02	95
GO:00458601	Colorectum	SER	positive regulation of protein kinase activity	79/2897	386/18723	4.85e-03	3.79e-02	79
GO:00719001	Colorectum	SER	regulation of protein serine/threonine kinase activity	74/2897	359/18723	5.22e-03	3.96e-02	74
GO:00336742	Colorectum	MSS	positive regulation of kinase activity	122/3467	467/18723	2.50e-05	5.21e-04	122
GO:00458602	Colorectum	MSS	positive regulation of protein kinase activity	102/3467	386/18723	6.93e-05	1.20e-03	102
GO:00719002	Colorectum	MSS	regulation of protein serine/threonine kinase activity	93/3467	359/18723	2.98e-04	3.91e-03	93
GO:00719021	Colorectum	MSS	positive regulation of protein serine/threonine kinase activity	55/3467	200/18723	1.12e-03	1.11e-02	55
GO:00336743	Colorectum	MSI-H	positive regulation of kinase activity	53/1319	467/18723	3.99e-04	8.98e-03	53
GO:00458603	Colorectum	MSI-H	positive regulation of protein kinase activity	45/1319	386/18723	6.03e-04	1.19e-02	45
GO:00719003	Colorectum	FAP	regulation of protein serine/threonine kinase activity	78/2622	359/18723	3.99e-05	8.48e-04	78
GO:00458604	Colorectum	FAP	positive regulation of protein kinase activity	77/2622	386/18723	7.31e-04	7.81e-03	77
GO:00719022	Colorectum	FAP	positive regulation of protein serine/threonine kinase activity	45/2622	200/18723	7.36e-04	7.83e-03	45
GO:00336744	Colorectum	FAP	positive regulation of kinase activity	89/2622	467/18723	1.33e-03	1.22e-02	89
GO:003367414	Endometrium	AEH	positive regulation of kinase activity	78/2100	467/18723	2.03e-04	2.54e-03	78
GO:00458609	Endometrium	AEH	positive regulation of protein kinase activity	66/2100	386/18723	3.14e-04	3.53e-03	66
GO:00719008	Endometrium	AEH	regulation of protein serine/threonine kinase activity	61/2100	359/18723	6.11e-04	5.98e-03	61

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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

DAZAP2

SNV

Missense_Mutation

novel

c.614N>G

p.Val205Gly

p.V205G

Q15038

protein_coding

deleterious_low_confidence(0)

benign(0.031)

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DAZAP2

insertion

In_Frame_Ins

novel

c.613_614insGCCAGAACCCCA

p.Val205delinsGlyGlnAsnProIle

p.V205delinsGQNPI

Q15038

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DAZAP2

insertion

Nonsense_Mutation

novel

c.602_603insGTAATCCCAGCTACTTGGGAGGCTAAGACAGGAGAATC

p.Met202Ter

p.M202*

Q15038

protein_coding

TCGA-A8-A0A4-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

DAZAP2

SNV

Missense_Mutation

novel

c.483N>G

p.Phe161Leu

p.F161L

Q15038

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.627)

TCGA-EA-A97N-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

DAZAP2

SNV

Missense_Mutation

novel

c.299C>T

p.Pro100Leu

p.P100L

Q15038

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.998)

TCGA-VS-A957-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

DAZAP2

SNV

Missense_Mutation

novel

c.233N>C

p.Val78Ala

p.V78A

Q15038

protein_coding

deleterious_low_confidence(0.01)

benign(0.031)

TCGA-AX-A0J1-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

DAZAP2

SNV

Missense_Mutation

novel

c.299C>T

p.Pro100Leu

p.P100L

Q15038

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.998)

TCGA-B5-A1MX-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Hormone Therapy

megace

DAZAP2

SNV

Missense_Mutation

novel

c.307A>G

p.Thr103Ala

p.T103A

Q15038

protein_coding

deleterious_low_confidence(0.03)

benign(0)

TCGA-B5-A1MX-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Hormone Therapy

megace

DAZAP2

SNV

Missense_Mutation

novel

c.190N>A

p.Ala64Thr

p.A64T

Q15038

protein_coding

tolerated_low_confidence(0.06)

possibly_damaging(0.792)

TCGA-B5-A3FC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

DAZAP2

SNV

Missense_Mutation

novel

c.223G>A

p.Ala75Thr

p.A75T

Q15038

protein_coding

tolerated_low_confidence(0.07)

possibly_damaging(0.87)

TCGA-D1-A175-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

paclitaxel

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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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