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: NCOA3

Gene summary for NCOA3

Gene summary.

Gene information	Species	Human
	Gene symbol	NCOA3
	Gene ID	8202
	Gene name	nuclear receptor coactivator 3
	Gene Alias	ACTR
	Cytomap	20q13.12
	Gene Type	protein-coding
	GO ID	GO:0006139
	UniProtAcc	Q59EE8

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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
8202	NCOA3	CCI_1	Human	Cervix	CC	1.58e-09	1.02e+00	0.528
8202	NCOA3	CCI_2	Human	Cervix	CC	8.80e-06	1.06e+00	0.5249
8202	NCOA3	CCI_3	Human	Cervix	CC	3.77e-24	1.48e+00	0.516
8202	NCOA3	Tumor	Human	Cervix	CC	1.66e-03	2.72e-01	0.1241
8202	NCOA3	sample3	Human	Cervix	CC	3.29e-10	3.62e-01	0.1387
8202	NCOA3	T3	Human	Cervix	CC	2.49e-10	3.63e-01	0.1389
8202	NCOA3	HTA11_3410_2000001011	Human	Colorectum	AD	7.34e-05	-3.41e-01	0.0155
8202	NCOA3	HTA11_99999970781_79442	Human	Colorectum	MSS	3.33e-06	-3.01e-01	0.294
8202	NCOA3	A002-C-010	Human	Colorectum	FAP	3.08e-02	-1.62e-01	0.242
8202	NCOA3	A001-C-207	Human	Colorectum	FAP	3.01e-04	-2.56e-01	0.1278
8202	NCOA3	A015-C-203	Human	Colorectum	FAP	2.23e-21	-3.49e-01	-0.1294
8202	NCOA3	A015-C-204	Human	Colorectum	FAP	4.91e-07	-3.52e-01	-0.0228
8202	NCOA3	A014-C-040	Human	Colorectum	FAP	1.37e-03	-3.34e-01	-0.1184
8202	NCOA3	A002-C-201	Human	Colorectum	FAP	8.39e-13	-3.47e-01	0.0324
8202	NCOA3	A001-C-119	Human	Colorectum	FAP	1.82e-04	-2.52e-01	-0.1557
8202	NCOA3	A001-C-108	Human	Colorectum	FAP	6.07e-14	-3.17e-01	-0.0272
8202	NCOA3	A002-C-205	Human	Colorectum	FAP	3.16e-21	-3.67e-01	-0.1236
8202	NCOA3	A015-C-005	Human	Colorectum	FAP	1.14e-02	-2.11e-01	-0.0336
8202	NCOA3	A015-C-006	Human	Colorectum	FAP	3.50e-15	-5.04e-01	-0.0994
8202	NCOA3	A015-C-106	Human	Colorectum	FAP	2.34e-06	-1.98e-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
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
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:00085446	Cervix	CC	epidermis development	83/2311	324/18723	3.91e-11	8.54e-09	83
GO:00435884	Cervix	CC	skin development	71/2311	263/18723	8.04e-11	1.46e-08	71
GO:00302164	Cervix	CC	keratinocyte differentiation	42/2311	139/18723	1.74e-08	1.28e-06	42
GO:00099137	Cervix	CC	epidermal cell differentiation	53/2311	202/18723	5.48e-08	3.25e-06	53
GO:00456822	Cervix	CC	regulation of epidermis development	22/2311	65/18723	5.56e-06	1.38e-04	22
GO:00456042	Cervix	CC	regulation of epidermal cell differentiation	20/2311	58/18723	1.07e-05	2.33e-04	20
GO:00456163	Cervix	CC	regulation of keratinocyte differentiation	14/2311	37/18723	6.97e-05	9.81e-04	14
GO:00323556	Cervix	CC	response to estradiol	34/2311	141/18723	8.19e-05	1.11e-03	34
GO:00308563	Cervix	CC	regulation of epithelial cell differentiation	36/2311	154/18723	1.02e-04	1.31e-03	36
GO:00165705	Cervix	CC	histone modification	84/2311	463/18723	1.70e-04	2.01e-03	84
GO:00513021	Cervix	CC	regulation of cell division	39/2311	177/18723	2.05e-04	2.33e-03	39
GO:00987275	Cervix	CC	maintenance of cell number	30/2311	134/18723	7.98e-04	7.00e-03	30
GO:00198274	Cervix	CC	stem cell population maintenance	29/2311	131/18723	1.17e-03	9.47e-03	29
GO:0017145	Cervix	CC	stem cell division	9/2311	30/18723	8.28e-03	4.28e-02	9
GO:00182054	Cervix	CC	peptidyl-lysine modification	62/2311	376/18723	1.04e-02	4.97e-02	62
GO:0009913	Colorectum	AD	epidermal cell differentiation	58/3918	202/18723	5.16e-03	3.42e-02	58
GO:0008544	Colorectum	AD	epidermis development	87/3918	324/18723	5.99e-03	3.76e-02	87
GO:0016570	Colorectum	MSS	histone modification	113/3467	463/18723	8.37e-04	8.68e-03	113
GO:00099131	Colorectum	MSS	epidermal cell differentiation	52/3467	202/18723	6.59e-03	4.38e-02	52
GO:00165701	Colorectum	FAP	histone modification	94/2622	463/18723	1.06e-04	1.76e-03	94

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0491520	Cervix	CC	Estrogen signaling pathway	44/1267	138/8465	3.55e-07	3.97e-06	2.35e-06	44
hsa0491918	Cervix	CC	Thyroid hormone signaling pathway	33/1267	121/8465	3.11e-04	1.65e-03	9.78e-04	33
hsa015223	Cervix	CC	Endocrine resistance	28/1267	98/8465	3.82e-04	1.87e-03	1.11e-03	28
hsa05224	Cervix	CC	Breast cancer	32/1267	147/8465	1.66e-02	4.88e-02	2.88e-02	32
hsa04915110	Cervix	CC	Estrogen signaling pathway	44/1267	138/8465	3.55e-07	3.97e-06	2.35e-06	44
hsa0491919	Cervix	CC	Thyroid hormone signaling pathway	33/1267	121/8465	3.11e-04	1.65e-03	9.78e-04	33
hsa0152212	Cervix	CC	Endocrine resistance	28/1267	98/8465	3.82e-04	1.87e-03	1.11e-03	28
hsa052241	Cervix	CC	Breast cancer	32/1267	147/8465	1.66e-02	4.88e-02	2.88e-02	32
hsa04919	Colorectum	AD	Thyroid hormone signaling pathway	51/2092	121/8465	1.71e-05	1.73e-04	1.10e-04	51
hsa049191	Colorectum	AD	Thyroid hormone signaling pathway	51/2092	121/8465	1.71e-05	1.73e-04	1.10e-04	51
hsa049194	Colorectum	MSS	Thyroid hormone signaling pathway	46/1875	121/8465	5.04e-05	4.97e-04	3.05e-04	46
hsa049152	Colorectum	MSS	Estrogen signaling pathway	48/1875	138/8465	4.23e-04	3.08e-03	1.89e-03	48
hsa049195	Colorectum	MSS	Thyroid hormone signaling pathway	46/1875	121/8465	5.04e-05	4.97e-04	3.05e-04	46
hsa049153	Colorectum	MSS	Estrogen signaling pathway	48/1875	138/8465	4.23e-04	3.08e-03	1.89e-03	48
hsa049198	Colorectum	FAP	Thyroid hormone signaling pathway	41/1404	121/8465	2.28e-06	4.28e-05	2.60e-05	41
hsa049199	Colorectum	FAP	Thyroid hormone signaling pathway	41/1404	121/8465	2.28e-06	4.28e-05	2.60e-05	41
hsa0491910	Colorectum	CRC	Thyroid hormone signaling pathway	35/1091	121/8465	2.05e-06	6.85e-05	4.64e-05	35
hsa049154	Colorectum	CRC	Estrogen signaling pathway	29/1091	138/8465	4.83e-03	2.66e-02	1.80e-02	29
hsa0491911	Colorectum	CRC	Thyroid hormone signaling pathway	35/1091	121/8465	2.05e-06	6.85e-05	4.64e-05	35
hsa049155	Colorectum	CRC	Estrogen signaling pathway	29/1091	138/8465	4.83e-03	2.66e-02	1.80e-02	29

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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

NCOA3

SNV

Missense_Mutation

c.3178N>T

p.Leu1060Phe

p.L1060F

Q9Y6Q9

protein_coding

tolerated(0.05)

benign(0.25)

TCGA-A7-A26H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

NCOA3

SNV

Missense_Mutation

c.1643T>G

p.Leu548Trp

p.L548W

Q9Y6Q9

protein_coding

deleterious(0.01)

possibly_damaging(0.874)

TCGA-A8-A08T-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

NCOA3

SNV

Missense_Mutation

c.241C>A

p.Gln81Lys

p.Q81K

Q9Y6Q9

protein_coding

deleterious(0)

possibly_damaging(0.709)

TCGA-A8-A0A7-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

NCOA3

SNV

Missense_Mutation

c.3410C>G

p.Ser1137Cys

p.S1137C

Q9Y6Q9

protein_coding

deleterious(0.01)

possibly_damaging(0.827)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NCOA3

SNV

Missense_Mutation

rs374724210

c.1715N>T

p.Gly572Val

p.G572V

Q9Y6Q9

protein_coding

deleterious(0)

possibly_damaging(0.581)

TCGA-AC-A2QI-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

cytoxan

NCOA3

SNV

Missense_Mutation

c.1625N>T

p.Ser542Leu

p.S542L

Q9Y6Q9

protein_coding

deleterious(0.01)

benign(0.119)

TCGA-AR-A0TQ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

NCOA3

SNV

Missense_Mutation

c.1234N>G

p.Pro412Ala

p.P412A

Q9Y6Q9

protein_coding

tolerated(0.81)

benign(0)

TCGA-BH-A0WA-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NCOA3

SNV

Missense_Mutation

c.526T>C

p.Ser176Pro

p.S176P

Q9Y6Q9

protein_coding

deleterious(0.04)

benign(0.279)

TCGA-C8-A274-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

NCOA3

SNV

Missense_Mutation

rs148634537

c.4010N>T

p.Ser1337Leu

p.S1337L

Q9Y6Q9

protein_coding

deleterious(0.02)

possibly_damaging(0.621)

TCGA-D8-A140-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin+cyclophosphamid

NCOA3

SNV

Missense_Mutation

c.3934C>A

p.Gln1312Lys

p.Q1312K

Q9Y6Q9

protein_coding

deleterious(0.02)

benign(0.038)

TCGA-D8-A1J8-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

nolvadex

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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
8202	NCOA3	NUCLEAR HORMONE RECEPTOR, DRUGGABLE GENOME, ENZYME		TAMOXIFEN	TAMOXIFEN	12618500
8202	NCOA3	NUCLEAR HORMONE RECEPTOR, DRUGGABLE GENOME, ENZYME		TCMDC-123764	CHEMBL533226
8202	NCOA3	NUCLEAR HORMONE RECEPTOR, DRUGGABLE GENOME, ENZYME		METHYLTHIONINIUM CHLORIDE	METHYLTHIONINIUM CHLORIDE
8202	NCOA3	NUCLEAR HORMONE RECEPTOR, DRUGGABLE GENOME, ENZYME		CYTARABINE	CYTARABINE
8202	NCOA3	NUCLEAR HORMONE RECEPTOR, DRUGGABLE GENOME, ENZYME		TCMDC-137788	CHEMBL587564
8202	NCOA3	NUCLEAR HORMONE RECEPTOR, DRUGGABLE GENOME, ENZYME		METHOTREXATE	METHOTREXATE
8202	NCOA3	NUCLEAR HORMONE RECEPTOR, DRUGGABLE GENOME, ENZYME		ETOPOSIDE	ETOPOSIDE
8202	NCOA3	NUCLEAR HORMONE RECEPTOR, DRUGGABLE GENOME, ENZYME		IRINOTECAN HYDROCHLORIDE HYDRATE	IRINOTECAN HYDROCHLORIDE HYDRATE
8202	NCOA3	NUCLEAR HORMONE RECEPTOR, DRUGGABLE GENOME, ENZYME		DNDI1417478	CHEMBL1972216

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