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: NCOR2

Gene summary for NCOR2

Gene summary.

Gene information	Species	Human
	Gene symbol	NCOR2
	Gene ID	9612
	Gene name	nuclear receptor corepressor 2
	Gene Alias	CTG26
	Cytomap	12q24.31
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	C9JE98

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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
9612	NCOR2	CCI_1	Human	Cervix	CC	3.15e-04	8.64e-01	0.528
9612	NCOR2	CCI_3	Human	Cervix	CC	1.54e-07	7.68e-01	0.516
9612	NCOR2	L1	Human	Cervix	CC	1.84e-02	-2.45e-01	0.0802
9612	NCOR2	HTA11_3410_2000001011	Human	Colorectum	AD	4.74e-08	3.03e-01	0.0155
9612	NCOR2	HTA11_2487_2000001011	Human	Colorectum	SER	1.51e-05	5.68e-01	-0.1808
9612	NCOR2	HTA11_1938_2000001011	Human	Colorectum	AD	5.15e-07	6.43e-01	-0.0811
9612	NCOR2	HTA11_347_2000001011	Human	Colorectum	AD	1.63e-07	3.47e-01	-0.1954
9612	NCOR2	HTA11_411_2000001011	Human	Colorectum	SER	7.31e-06	8.97e-01	-0.2602
9612	NCOR2	HTA11_696_2000001011	Human	Colorectum	AD	2.71e-16	5.81e-01	-0.1464
9612	NCOR2	HTA11_866_2000001011	Human	Colorectum	AD	2.07e-07	4.46e-01	-0.1001
9612	NCOR2	HTA11_1391_2000001011	Human	Colorectum	AD	3.79e-12	8.98e-01	-0.059
9612	NCOR2	HTA11_546_2000001011	Human	Colorectum	AD	1.27e-02	5.21e-01	-0.0842
9612	NCOR2	HTA11_866_3004761011	Human	Colorectum	AD	5.22e-07	4.49e-01	0.096
9612	NCOR2	HTA11_7696_3000711011	Human	Colorectum	AD	1.37e-13	6.16e-01	0.0674
9612	NCOR2	HTA11_6818_2000001011	Human	Colorectum	AD	8.19e-09	8.32e-01	0.0112
9612	NCOR2	HTA11_6818_2000001021	Human	Colorectum	AD	1.58e-10	7.42e-01	0.0588
9612	NCOR2	HTA11_99999965104_69814	Human	Colorectum	MSS	1.97e-09	5.18e-01	0.281
9612	NCOR2	HTA11_99999971662_82457	Human	Colorectum	MSS	1.15e-14	6.73e-01	0.3859
9612	NCOR2	HTA11_99999973899_84307	Human	Colorectum	MSS	2.19e-03	5.02e-01	0.2585
9612	NCOR2	HTA11_99999974143_84620	Human	Colorectum	MSS	1.36e-07	5.01e-01	0.3005

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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:004854510	Cervix	CC	response to steroid hormone	74/2311	339/18723	5.71e-07	2.09e-05	74
GO:00305229	Cervix	CC	intracellular receptor signaling pathway	60/2311	265/18723	1.89e-06	5.97e-05	60
GO:00485118	Cervix	CC	rhythmic process	65/2311	298/18723	2.79e-06	8.04e-05	65
GO:005087810	Cervix	CC	regulation of body fluid levels	78/2311	379/18723	3.20e-06	8.77e-05	78
GO:004873210	Cervix	CC	gland development	84/2311	436/18723	1.93e-05	3.54e-04	84
GO:00323556	Cervix	CC	response to estradiol	34/2311	141/18723	8.19e-05	1.11e-03	34
GO:00448492	Cervix	CC	estrous cycle	7/2311	16/18723	1.79e-03	1.34e-02	7
GO:00713839	Cervix	CC	cellular response to steroid hormone stimulus	40/2311	204/18723	1.93e-03	1.42e-02	40
GO:00305188	Cervix	CC	intracellular steroid hormone receptor signaling pathway	25/2311	116/18723	3.59e-03	2.30e-02	25
GO:00308797	Cervix	CC	mammary gland development	28/2311	137/18723	4.74e-03	2.83e-02	28
GO:00609647	Cervix	CC	regulation of gene silencing by miRNA	13/2311	49/18723	5.34e-03	3.10e-02	13
GO:00305218	Cervix	CC	androgen receptor signaling pathway	12/2311	44/18723	5.76e-03	3.30e-02	12
GO:00351966	Cervix	CC	production of miRNAs involved in gene silencing by miRNA	13/2311	52/18723	9.09e-03	4.60e-02	13
GO:00601476	Cervix	CC	regulation of posttranscriptional gene silencing	13/2311	52/18723	9.09e-03	4.60e-02	13
GO:0048732	Colorectum	AD	gland development	149/3918	436/18723	6.07e-11	6.33e-09	149
GO:0071383	Colorectum	AD	cellular response to steroid hormone stimulus	73/3918	204/18723	6.31e-07	2.24e-05	73
GO:0030879	Colorectum	AD	mammary gland development	53/3918	137/18723	1.46e-06	4.58e-05	53
GO:0030522	Colorectum	AD	intracellular receptor signaling pathway	87/3918	265/18723	3.69e-06	1.03e-04	87
GO:0043401	Colorectum	AD	steroid hormone mediated signaling pathway	51/3918	136/18723	6.52e-06	1.63e-04	51
GO:0048511	Colorectum	AD	rhythmic process	94/3918	298/18723	1.00e-05	2.34e-04	94

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0516920	Cervix	CC	Epstein-Barr virus infection	57/1267	202/8465	7.30e-07	7.39e-06	4.37e-06	57
hsa04330	Cervix	CC	Notch signaling pathway	17/1267	62/8465	7.99e-03	2.56e-02	1.51e-02	17
hsa05169110	Cervix	CC	Epstein-Barr virus infection	57/1267	202/8465	7.30e-07	7.39e-06	4.37e-06	57
hsa043301	Cervix	CC	Notch signaling pathway	17/1267	62/8465	7.99e-03	2.56e-02	1.51e-02	17
hsa05169	Colorectum	MSS	Epstein-Barr virus infection	63/1875	202/8465	1.63e-03	8.98e-03	5.50e-03	63
hsa051691	Colorectum	MSS	Epstein-Barr virus infection	63/1875	202/8465	1.63e-03	8.98e-03	5.50e-03	63
hsa05169210	Esophagus	ESCC	Epstein-Barr virus infection	151/4205	202/8465	1.55e-13	3.45e-12	1.77e-12	151
hsa043306	Esophagus	ESCC	Notch signaling pathway	42/4205	62/8465	2.97e-03	7.97e-03	4.08e-03	42
hsa0516937	Esophagus	ESCC	Epstein-Barr virus infection	151/4205	202/8465	1.55e-13	3.45e-12	1.77e-12	151
hsa0433013	Esophagus	ESCC	Notch signaling pathway	42/4205	62/8465	2.97e-03	7.97e-03	4.08e-03	42
hsa0516921	Liver	HCC	Epstein-Barr virus infection	128/4020	202/8465	3.17e-06	2.79e-05	1.55e-05	128
hsa0516931	Liver	HCC	Epstein-Barr virus infection	128/4020	202/8465	3.17e-06	2.79e-05	1.55e-05	128
hsa0516916	Lung	IAC	Epstein-Barr virus infection	40/1053	202/8465	1.72e-03	9.66e-03	6.41e-03	40
hsa0516917	Lung	IAC	Epstein-Barr virus infection	40/1053	202/8465	1.72e-03	9.66e-03	6.41e-03	40
hsa0516928	Oral cavity	OSCC	Epstein-Barr virus infection	144/3704	202/8465	1.08e-15	3.60e-14	1.83e-14	144
hsa043305	Oral cavity	OSCC	Notch signaling pathway	44/3704	62/8465	1.26e-05	5.55e-05	2.83e-05	44
hsa05169113	Oral cavity	OSCC	Epstein-Barr virus infection	144/3704	202/8465	1.08e-15	3.60e-14	1.83e-14	144
hsa0433012	Oral cavity	OSCC	Notch signaling pathway	44/3704	62/8465	1.26e-05	5.55e-05	2.83e-05	44
hsa0516929	Oral cavity	LP	Epstein-Barr virus infection	106/2418	202/8465	4.30e-13	9.54e-12	6.15e-12	106
hsa0516936	Oral cavity	LP	Epstein-Barr virus infection	106/2418	202/8465	4.30e-13	9.54e-12	6.15e-12	106

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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
NCOR2	PERI	Stomach	CAG with IM	TAFA1,RNF31,ISG15, etc.	6.98e-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

NCOR2

SNV

Missense_Mutation

novel

c.1321C>T

p.Arg441Trp

p.R441W

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

NCOR2

SNV

Missense_Mutation

c.5427N>T

p.Glu1809Asp

p.E1809D

protein_coding

tolerated(0.15)

benign(0.122)

TCGA-A1-A0SO-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

NCOR2

SNV

Missense_Mutation

c.2080N>A

p.Ala694Thr

p.A694T

protein_coding

tolerated(0.43)

benign(0.003)

TCGA-BH-A18T-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NCOR2

SNV

Missense_Mutation

c.1463N>A

p.Arg488Gln

p.R488Q

protein_coding

deleterious(0.02)

probably_damaging(0.975)

TCGA-C8-A26X-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

NCOR2

SNV

Missense_Mutation

rs373295499

c.3775C>T

p.Arg1259Trp

p.R1259W

protein_coding

deleterious(0)

probably_damaging(0.984)

TCGA-GM-A2DF-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxol

NCOR2

insertion

Nonsense_Mutation

novel

c.3723_3724insGATGTTTAA

p.Gly1241_Thr1242insAspValTer

p.G1241_T1242insDV*

protein_coding

TCGA-A2-A0CT-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

NCOR2

insertion

Frame_Shift_Ins

novel

c.1832_1833insA

p.Ser612GlufsTer39

p.S612Efs*39

protein_coding

TCGA-A8-A091-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

NCOR2

deletion

Frame_Shift_Del

c.1620delN

p.Asn540LysfsTer70

p.N540Kfs*70

protein_coding

TCGA-GM-A2DL-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

NCOR2

SNV

Missense_Mutation

c.3442N>A

p.Val1148Ile

p.V1148I

protein_coding

tolerated(1)

benign(0.006)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

NCOR2

SNV

Missense_Mutation

novel

c.325N>T

p.Arg109Trp

p.R109W

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-C5-A2LZ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

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
9612	NCOR2	NUCLEAR HORMONE RECEPTOR, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		9,10-PHENANTHRENEQUINONE	9,10-PHENANTHRENEQUINONE
9612	NCOR2	NUCLEAR HORMONE RECEPTOR, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		GNF-PF-2893	CHEMBL312032
9612	NCOR2	NUCLEAR HORMONE RECEPTOR, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		BENZBROMARONE	BENZBROMARONE

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