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: NCOA2

Gene summary for NCOA2

Gene summary.

Gene information	Species	Human
	Gene symbol	NCOA2
	Gene ID	10499
	Gene name	nuclear receptor coactivator 2
	Gene Alias	GRIP1
	Cytomap	8q13.3
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	Q15596

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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
10499	NCOA2	LZE7T	Human	Esophagus	ESCC	9.82e-03	7.49e-02	0.0667
10499	NCOA2	LZE8T	Human	Esophagus	ESCC	1.88e-05	7.25e-02	0.067
10499	NCOA2	LZE20T	Human	Esophagus	ESCC	3.34e-10	2.49e-01	0.0662
10499	NCOA2	LZE24T	Human	Esophagus	ESCC	4.37e-14	3.55e-01	0.0596
10499	NCOA2	LZE21T	Human	Esophagus	ESCC	1.35e-05	1.70e-01	0.0655
10499	NCOA2	LZE6T	Human	Esophagus	ESCC	3.35e-03	7.23e-02	0.0845
10499	NCOA2	P1T-E	Human	Esophagus	ESCC	2.63e-05	2.47e-01	0.0875
10499	NCOA2	P2T-E	Human	Esophagus	ESCC	1.84e-15	2.66e-01	0.1177
10499	NCOA2	P4T-E	Human	Esophagus	ESCC	1.97e-06	4.59e-02	0.1323
10499	NCOA2	P5T-E	Human	Esophagus	ESCC	2.50e-04	6.86e-03	0.1327
10499	NCOA2	P8T-E	Human	Esophagus	ESCC	2.03e-22	2.38e-01	0.0889
10499	NCOA2	P9T-E	Human	Esophagus	ESCC	1.25e-12	1.06e-01	0.1131
10499	NCOA2	P10T-E	Human	Esophagus	ESCC	1.37e-14	2.10e-01	0.116
10499	NCOA2	P12T-E	Human	Esophagus	ESCC	7.68e-14	2.91e-01	0.1122
10499	NCOA2	P15T-E	Human	Esophagus	ESCC	4.84e-24	2.78e-01	0.1149
10499	NCOA2	P16T-E	Human	Esophagus	ESCC	2.97e-21	4.11e-01	0.1153
10499	NCOA2	P17T-E	Human	Esophagus	ESCC	1.89e-04	1.23e-01	0.1278
10499	NCOA2	P20T-E	Human	Esophagus	ESCC	1.08e-19	2.07e-01	0.1124
10499	NCOA2	P21T-E	Human	Esophagus	ESCC	1.15e-13	1.14e-01	0.1617
10499	NCOA2	P22T-E	Human	Esophagus	ESCC	4.57e-06	7.37e-02	0.1236

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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:004854510	Cervix	CC	response to steroid hormone	74/2311	339/18723	5.71e-07	2.09e-05	74
GO:00485118	Cervix	CC	rhythmic process	65/2311	298/18723	2.79e-06	8.04e-05	65
GO:190165410	Cervix	CC	response to ketone	45/2311	194/18723	1.83e-05	3.44e-04	45
GO:00076238	Cervix	CC	circadian rhythm	46/2311	210/18723	6.76e-05	9.60e-04	46
GO:00325704	Cervix	CC	response to progesterone	13/2311	37/18723	2.99e-04	3.21e-03	13
GO:00329226	Cervix	CC	circadian regulation of gene expression	18/2311	68/18723	1.18e-03	9.56e-03	18
GO:0007623	Colorectum	AD	circadian rhythm	72/3918	210/18723	4.50e-06	1.21e-04	72
GO:0048511	Colorectum	AD	rhythmic process	94/3918	298/18723	1.00e-05	2.34e-04	94
GO:0048545	Colorectum	AD	response to steroid hormone	104/3918	339/18723	1.33e-05	2.90e-04	104
GO:0019318	Colorectum	AD	hexose metabolic process	77/3918	237/18723	1.96e-05	4.01e-04	77
GO:0044262	Colorectum	AD	cellular carbohydrate metabolic process	87/3918	283/18723	6.00e-05	1.01e-03	87
GO:0005996	Colorectum	AD	monosaccharide metabolic process	80/3918	257/18723	7.31e-05	1.17e-03	80
GO:0006006	Colorectum	AD	glucose metabolic process	62/3918	196/18723	2.76e-04	3.39e-03	62
GO:0006109	Colorectum	AD	regulation of carbohydrate metabolic process	55/3918	178/18723	1.10e-03	1.01e-02	55
GO:1901654	Colorectum	AD	response to ketone	59/3918	194/18723	1.14e-03	1.04e-02	59
GO:0062012	Colorectum	AD	regulation of small molecule metabolic process	93/3918	334/18723	1.46e-03	1.24e-02	93
GO:00485451	Colorectum	SER	response to steroid hormone	80/2897	339/18723	5.15e-05	1.25e-03	80
GO:00076231	Colorectum	SER	circadian rhythm	54/2897	210/18723	7.98e-05	1.77e-03	54
GO:00193181	Colorectum	SER	hexose metabolic process	56/2897	237/18723	6.19e-04	8.42e-03	56
GO:00059961	Colorectum	SER	monosaccharide metabolic process	59/2897	257/18723	9.65e-04	1.15e-02	59

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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
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
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
hsa049192	Colorectum	SER	Thyroid hormone signaling pathway	40/1580	121/8465	1.02e-04	1.06e-03	7.67e-04	40
hsa04915	Colorectum	SER	Estrogen signaling pathway	38/1580	138/8465	6.51e-03	3.68e-02	2.67e-02	38
hsa049193	Colorectum	SER	Thyroid hormone signaling pathway	40/1580	121/8465	1.02e-04	1.06e-03	7.67e-04	40
hsa049151	Colorectum	SER	Estrogen signaling pathway	38/1580	138/8465	6.51e-03	3.68e-02	2.67e-02	38
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

NCOA2

SNV

Missense_Mutation

c.2933N>A

p.Gly978Glu

p.G978E

Q15596

protein_coding

tolerated(0.11)

possibly_damaging(0.621)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NCOA2

SNV

Missense_Mutation

c.826N>T

p.Leu276Phe

p.L276F

Q15596

protein_coding

deleterious(0.01)

benign(0.086)

TCGA-BH-A0W7-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

NCOA2

SNV

Missense_Mutation

c.703N>A

p.Pro235Thr

p.P235T

Q15596

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-E9-A1N4-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

NCOA2

SNV

Missense_Mutation

c.254A>T

p.Glu85Val

p.E85V

Q15596

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-EW-A1IZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

taxotere

NCOA2

SNV

Missense_Mutation

novel

c.109N>T

p.Arg37Cys

p.R37C

Q15596

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-UL-AAZ6-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

herceptin

NCOA2

insertion

Frame_Shift_Ins

novel

c.2845_2846insGGTTTAGAAC

p.Met949ArgfsTer68

p.M949Rfs*68

Q15596

protein_coding

TCGA-E9-A1NI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

NCOA2

SNV

Missense_Mutation

rs373466036

c.3137N>T

p.Ala1046Val

p.A1046V

Q15596

protein_coding

tolerated(0.31)

benign(0.007)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

NCOA2

SNV

Missense_Mutation

rs777306143

c.2485N>A

p.Ala829Thr

p.A829T

Q15596

protein_coding

tolerated(0.25)

benign(0.005)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

NCOA2

SNV

Missense_Mutation

novel

c.1830N>T

p.Lys610Asn

p.K610N

Q15596

protein_coding

deleterious(0.02)

benign(0.138)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

NCOA2

SNV

Missense_Mutation

rs375519556

c.3389C>T

p.Ala1130Val

p.A1130V

Q15596

protein_coding

deleterious(0.02)

benign(0.011)

TCGA-EA-A410-01

Cervix

cervical & endocervical cancer

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
10499	NCOA2	CLINICALLY ACTIONABLE, ENZYME, TRANSCRIPTION FACTOR, NUCLEAR HORMONE RECEPTOR, TRANSCRIPTION FACTOR COMPLEX		METHYLTHIONINIUM CHLORIDE	METHYLTHIONINIUM CHLORIDE

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