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: ADNP

Gene summary for ADNP

Gene summary.

Gene information	Species	Human
	Gene symbol	ADNP
	Gene ID	23394
	Gene name	activity dependent neuroprotector homeobox
	Gene Alias	ADNP1
	Cytomap	20q13.13
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	Q9H2P0

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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
23394	ADNP	CA_HPV_3	Human	Cervix	CC	4.59e-02	1.04e-01	0.0414
23394	ADNP	CCI_1	Human	Cervix	CC	3.01e-04	6.21e-01	0.528
23394	ADNP	CCI_2	Human	Cervix	CC	9.58e-11	8.44e-01	0.5249
23394	ADNP	CCI_3	Human	Cervix	CC	1.70e-16	9.09e-01	0.516
23394	ADNP	T3	Human	Cervix	CC	2.96e-04	1.44e-01	0.1389
23394	ADNP	HTA11_3410_2000001011	Human	Colorectum	AD	9.66e-08	-5.06e-01	0.0155
23394	ADNP	HTA11_5212_2000001011	Human	Colorectum	AD	1.01e-02	-5.70e-01	-0.2061
23394	ADNP	F007	Human	Colorectum	FAP	8.30e-03	8.30e-02	0.1176
23394	ADNP	A001-C-207	Human	Colorectum	FAP	2.66e-03	-9.62e-02	0.1278
23394	ADNP	A015-C-203	Human	Colorectum	FAP	5.30e-29	-3.39e-01	-0.1294
23394	ADNP	A015-C-204	Human	Colorectum	FAP	3.73e-05	-2.21e-01	-0.0228
23394	ADNP	A014-C-040	Human	Colorectum	FAP	1.37e-04	-1.58e-01	-0.1184
23394	ADNP	A002-C-201	Human	Colorectum	FAP	3.08e-16	-3.08e-01	0.0324
23394	ADNP	A001-C-119	Human	Colorectum	FAP	7.37e-08	-2.86e-01	-0.1557
23394	ADNP	A001-C-108	Human	Colorectum	FAP	6.00e-11	-1.44e-01	-0.0272
23394	ADNP	A002-C-205	Human	Colorectum	FAP	1.02e-24	-3.15e-01	-0.1236
23394	ADNP	A001-C-104	Human	Colorectum	FAP	2.73e-02	-7.39e-02	0.0184
23394	ADNP	A015-C-005	Human	Colorectum	FAP	1.03e-03	-1.57e-01	-0.0336
23394	ADNP	A015-C-006	Human	Colorectum	FAP	8.29e-17	-2.62e-01	-0.0994
23394	ADNP	A015-C-106	Human	Colorectum	FAP	3.51e-10	-2.48e-01	-0.0511

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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
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:0099177	Colorectum	CRC	regulation of trans-synaptic signaling	70/2078	440/18723	1.23e-03	1.38e-02	70
GO:00083613	Colorectum	CRC	regulation of cell size	34/2078	181/18723	1.47e-03	1.57e-02	34
GO:00435234	Colorectum	CRC	regulation of neuron apoptotic process	38/2078	212/18723	1.95e-03	1.96e-02	38
GO:00435241	Colorectum	CRC	negative regulation of neuron apoptotic process	28/2078	145/18723	2.43e-03	2.30e-02	28
GO:19018883	Colorectum	CRC	regulation of cell junction assembly	36/2078	204/18723	3.30e-03	2.84e-02	36
GO:00511003	Colorectum	CRC	negative regulation of binding	30/2078	162/18723	3.36e-03	2.87e-02	30
GO:00519621	Colorectum	CRC	positive regulation of nervous system development	44/2078	272/18723	6.71e-03	4.77e-02	44
GO:0051098111	Esophagus	ESCC	regulation of binding	251/8552	363/18723	6.73e-20	8.46e-18	251
GO:0071496111	Esophagus	ESCC	cellular response to external stimulus	215/8552	320/18723	4.29e-15	2.43e-13	215
GO:0031668111	Esophagus	ESCC	cellular response to extracellular stimulus	168/8552	246/18723	4.93e-13	2.23e-11	168
GO:004339320	Esophagus	ESCC	regulation of protein binding	135/8552	196/18723	3.69e-11	1.22e-09	135
GO:0016049110	Esophagus	ESCC	cell growth	289/8552	482/18723	1.29e-10	3.77e-09	289
GO:000155819	Esophagus	ESCC	regulation of cell growth	248/8552	414/18723	2.97e-09	6.45e-08	248
GO:0051100111	Esophagus	ESCC	negative regulation of binding	109/8552	162/18723	2.10e-08	4.03e-07	109
GO:0070997111	Esophagus	ESCC	neuron death	216/8552	361/18723	3.49e-08	6.45e-07	216
GO:003253520	Esophagus	ESCC	regulation of cellular component size	227/8552	383/18723	4.77e-08	8.60e-07	227
GO:0051402110	Esophagus	ESCC	neuron apoptotic process	148/8552	246/18723	3.08e-06	3.47e-05	148
GO:1901214111	Esophagus	ESCC	regulation of neuron death	186/8552	319/18723	3.35e-06	3.73e-05	186
GO:003209116	Esophagus	ESCC	negative regulation of protein binding	65/8552	94/18723	3.46e-06	3.82e-05	65
GO:004586018	Esophagus	ESCC	positive regulation of protein kinase activity	219/8552	386/18723	6.91e-06	6.97e-05	219

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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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
ADNP	CD8TEX	Oral cavity	NEOLP	CDC42,HNRNPH1,C1orf56, etc.	1.10e-02

∗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

ADNP

SNV

Missense_Mutation

novel

c.1603N>T

p.His535Tyr

p.H535Y

Q9H2P0

protein_coding

deleterious(0)

probably_damaging(0.932)

TCGA-3C-AALI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Poly E

Complete Response

ADNP

SNV

Missense_Mutation

c.2618N>G

p.Asp873Gly

p.D873G

Q9H2P0

protein_coding

tolerated_low_confidence(0.22)

benign(0.175)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ADNP

SNV

Missense_Mutation

c.2200G>A

p.Asp734Asn

p.D734N

Q9H2P0

protein_coding

tolerated(0.36)

benign(0)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ADNP

SNV

Missense_Mutation

novel

c.1363N>A

p.Leu455Ile

p.L455I

Q9H2P0

protein_coding

deleterious(0)

probably_damaging(0.993)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ADNP

SNV

Missense_Mutation

novel

c.976N>A

p.His326Asn

p.H326N

Q9H2P0

protein_coding

tolerated(0.17)

probably_damaging(0.956)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ADNP

SNV

Missense_Mutation

novel

c.2521N>C

p.Asp841His

p.D841H

Q9H2P0

protein_coding

deleterious(0.01)

possibly_damaging(0.536)

TCGA-AN-A0AJ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ADNP

SNV

Missense_Mutation

novel

c.1364T>C

p.Leu455Pro

p.L455P

Q9H2P0

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-AR-A0U0-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ADNP

SNV

Missense_Mutation

c.1041N>A

p.Met347Ile

p.M347I

Q9H2P0

protein_coding

tolerated(0.49)

benign(0)

TCGA-B6-A0IK-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

ADNP

SNV

Missense_Mutation

c.3244N>A

p.Asp1082Asn

p.D1082N

Q9H2P0

protein_coding

deleterious_low_confidence(0.01)

benign(0.173)

TCGA-BH-A0HP-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

doxorubicin

ADNP

SNV

Missense_Mutation

c.3087N>C

p.Lys1029Asn

p.K1029N

Q9H2P0

protein_coding

tolerated_low_confidence(0.43)

probably_damaging(0.981)

TCGA-BH-A0HP-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

doxorubicin

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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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