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: NCOR1

Gene summary for NCOR1

Gene summary.

Gene information	Species	Human
	Gene symbol	NCOR1
	Gene ID	9611
	Gene name	nuclear receptor corepressor 1
	Gene Alias	N-CoR
	Cytomap	17p12-p11.2
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	O75376

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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
9611	NCOR1	HTA11_3410_2000001011	Human	Colorectum	AD	4.83e-37	-7.84e-01	0.0155
9611	NCOR1	HTA11_2951_2000001011	Human	Colorectum	AD	5.96e-04	-6.65e-01	0.0216
9611	NCOR1	HTA11_347_2000001011	Human	Colorectum	AD	2.28e-18	7.34e-01	-0.1954
9611	NCOR1	HTA11_3361_2000001011	Human	Colorectum	AD	1.21e-06	-4.66e-01	-0.1207
9611	NCOR1	HTA11_866_3004761011	Human	Colorectum	AD	1.92e-03	-3.75e-01	0.096
9611	NCOR1	HTA11_4255_2000001011	Human	Colorectum	SER	1.11e-03	-5.03e-01	0.0446
9611	NCOR1	HTA11_8622_2000001021	Human	Colorectum	SER	1.25e-03	-6.07e-01	0.0528
9611	NCOR1	HTA11_10711_2000001011	Human	Colorectum	AD	1.45e-02	-3.95e-01	0.0338
9611	NCOR1	HTA11_7469_2000001011	Human	Colorectum	AD	5.59e-05	-2.61e-01	-0.0124
9611	NCOR1	HTA11_11156_2000001011	Human	Colorectum	AD	3.08e-03	-7.05e-01	0.0397
9611	NCOR1	HTA11_6818_2000001021	Human	Colorectum	AD	9.62e-08	-6.13e-01	0.0588
9611	NCOR1	HTA11_99999970781_79442	Human	Colorectum	MSS	6.40e-13	-4.93e-01	0.294
9611	NCOR1	HTA11_99999965062_69753	Human	Colorectum	MSI-H	1.39e-04	5.48e-01	0.3487
9611	NCOR1	HTA11_99999971662_82457	Human	Colorectum	MSS	7.03e-13	-5.96e-01	0.3859
9611	NCOR1	HTA11_99999973899_84307	Human	Colorectum	MSS	6.05e-21	-9.78e-01	0.2585
9611	NCOR1	HTA11_99999974143_84620	Human	Colorectum	MSS	1.15e-30	-7.25e-01	0.3005
9611	NCOR1	F007	Human	Colorectum	FAP	1.08e-03	-1.11e-01	0.1176
9611	NCOR1	A001-C-207	Human	Colorectum	FAP	3.22e-07	-2.28e-01	0.1278
9611	NCOR1	A015-C-203	Human	Colorectum	FAP	1.32e-36	-2.79e-01	-0.1294
9611	NCOR1	A015-C-204	Human	Colorectum	FAP	2.75e-06	-1.53e-01	-0.0228

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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
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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:007138318	Oral cavity	OSCC	cellular response to steroid hormone stimulus	112/7305	204/18723	2.82e-06	3.47e-05	112
GO:001969319	Oral cavity	OSCC	ribose phosphate metabolic process	199/7305	396/18723	2.97e-06	3.64e-05	199
GO:000925919	Oral cavity	OSCC	ribonucleotide metabolic process	189/7305	385/18723	3.18e-05	2.87e-04	189
GO:00421804	Oral cavity	OSCC	cellular ketone metabolic process	111/7305	211/18723	3.94e-05	3.45e-04	111
GO:004340116	Oral cavity	OSCC	steroid hormone mediated signaling pathway	76/7305	136/18723	4.76e-05	3.99e-04	76
GO:000762316	Oral cavity	OSCC	circadian rhythm	110/7305	210/18723	5.40e-05	4.48e-04	110
GO:003287310	Oral cavity	OSCC	negative regulation of stress-activated MAPK cascade	34/7305	51/18723	5.83e-05	4.80e-04	34
GO:007030310	Oral cavity	OSCC	negative regulation of stress-activated protein kinase signaling cascade	34/7305	51/18723	5.83e-05	4.80e-04	34
GO:000913217	Oral cavity	OSCC	nucleoside diphosphate metabolic process	70/7305	124/18723	6.03e-05	4.95e-04	70
GO:00072548	Oral cavity	OSCC	JNK cascade	90/7305	167/18723	6.49e-05	5.26e-04	90
GO:00463288	Oral cavity	OSCC	regulation of JNK cascade	74/7305	133/18723	7.22e-05	5.69e-04	74
GO:004693917	Oral cavity	OSCC	nucleotide phosphorylation	58/7305	101/18723	1.33e-04	9.44e-04	58
GO:007252120	Oral cavity	OSCC	purine-containing compound metabolic process	199/7305	416/18723	1.34e-04	9.53e-04	199
GO:000915020	Oral cavity	OSCC	purine ribonucleotide metabolic process	178/7305	368/18723	1.45e-04	1.02e-03	178
GO:000918518	Oral cavity	OSCC	ribonucleoside diphosphate metabolic process	60/7305	106/18723	1.78e-04	1.21e-03	60
GO:004346716	Oral cavity	OSCC	regulation of generation of precursor metabolites and energy	71/7305	130/18723	2.15e-04	1.41e-03	71
GO:00066317	Oral cavity	OSCC	fatty acid metabolic process	186/7305	390/18723	2.65e-04	1.69e-03	186
GO:000913519	Oral cavity	OSCC	purine nucleoside diphosphate metabolic process	58/7305	103/18723	2.73e-04	1.73e-03	58
GO:000917919	Oral cavity	OSCC	purine ribonucleoside diphosphate metabolic process	58/7305	103/18723	2.73e-04	1.73e-03	58
GO:00331437	Oral cavity	OSCC	regulation of intracellular steroid hormone receptor signaling pathway	44/7305	74/18723	2.89e-04	1.82e-03	44

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
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
hsa04350	Colorectum	SER	TGF-beta signaling pathway	31/1580	108/8465	7.00e-03	3.77e-02	2.74e-02	31
hsa049193	Colorectum	SER	Thyroid hormone signaling pathway	40/1580	121/8465	1.02e-04	1.06e-03	7.67e-04	40
hsa043501	Colorectum	SER	TGF-beta signaling pathway	31/1580	108/8465	7.00e-03	3.77e-02	2.74e-02	31
hsa049194	Colorectum	MSS	Thyroid hormone signaling pathway	46/1875	121/8465	5.04e-05	4.97e-04	3.05e-04	46
hsa049195	Colorectum	MSS	Thyroid hormone signaling pathway	46/1875	121/8465	5.04e-05	4.97e-04	3.05e-04	46
hsa049196	Colorectum	MSI-H	Thyroid hormone signaling pathway	21/797	121/8465	4.18e-03	4.10e-02	3.44e-02	21
hsa049197	Colorectum	MSI-H	Thyroid hormone signaling pathway	21/797	121/8465	4.18e-03	4.10e-02	3.44e-02	21
hsa049198	Colorectum	FAP	Thyroid hormone signaling pathway	41/1404	121/8465	2.28e-06	4.28e-05	2.60e-05	41
hsa05202	Colorectum	FAP	Transcriptional misregulation in cancer	45/1404	193/8465	9.19e-03	3.33e-02	2.03e-02	45
hsa049199	Colorectum	FAP	Thyroid hormone signaling pathway	41/1404	121/8465	2.28e-06	4.28e-05	2.60e-05	41
hsa052021	Colorectum	FAP	Transcriptional misregulation in cancer	45/1404	193/8465	9.19e-03	3.33e-02	2.03e-02	45
hsa0491910	Colorectum	CRC	Thyroid hormone signaling pathway	35/1091	121/8465	2.05e-06	6.85e-05	4.64e-05	35
hsa0491911	Colorectum	CRC	Thyroid hormone signaling pathway	35/1091	121/8465	2.05e-06	6.85e-05	4.64e-05	35
hsa0491928	Esophagus	ESCC	Thyroid hormone signaling pathway	78/4205	121/8465	6.79e-04	2.23e-03	1.14e-03	78
hsa043507	Esophagus	ESCC	TGF-beta signaling pathway	69/4205	108/8465	1.92e-03	5.54e-03	2.84e-03	69
hsa052028	Esophagus	ESCC	Transcriptional misregulation in cancer	116/4205	193/8465	2.08e-03	5.95e-03	3.05e-03	116
hsa015227	Esophagus	ESCC	Endocrine resistance	63/4205	98/8465	2.38e-03	6.58e-03	3.37e-03	63

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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
NCOR1	STM	Liver	Cirrhotic	SLC2A9,MARCH6,THOC1, etc.	3.10e-01
NCOR1	STM	Liver	HCC	SLC2A9,MARCH6,THOC1, etc.	1.89e-01

∗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

NCOR1

SNV

Missense_Mutation

novel

c.19C>T

p.Pro7Ser

p.P7S

O75376

protein_coding

deleterious(0)

possibly_damaging(0.621)

TCGA-3C-AALK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

docetaxel

NCOR1

SNV

Missense_Mutation

c.1591N>C

p.Glu531Gln

p.E531Q

O75376

protein_coding

tolerated(0.07)

benign(0.042)

TCGA-A1-A0SN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

NCOR1

SNV

Missense_Mutation

c.3488N>A

p.Gly1163Asp

p.G1163D

O75376

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-A2-A0CU-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

NCOR1

SNV

Missense_Mutation

c.7010N>T

p.Ser2337Phe

p.S2337F

O75376

protein_coding

deleterious(0)

probably_damaging(0.991)

TCGA-A8-A08R-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

NCOR1

SNV

Missense_Mutation

novel

c.2161G>A

p.Glu721Lys

p.E721K

O75376

protein_coding

deleterious(0.02)

probably_damaging(0.971)

TCGA-AC-A8OP-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NCOR1

SNV

Missense_Mutation

rs367758096

c.451N>A

p.Gly151Ser

p.G151S

O75376

protein_coding

tolerated(0.18)

benign(0.001)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NCOR1

SNV

Missense_Mutation

c.5725N>T

p.Pro1909Ser

p.P1909S

O75376

protein_coding

tolerated(0.09)

benign(0.162)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NCOR1

SNV

Missense_Mutation

c.5263N>T

p.Arg1755Cys

p.R1755C

O75376

protein_coding

deleterious(0)

probably_damaging(0.925)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NCOR1

SNV

Missense_Mutation

rs754505756

c.4882N>T

p.Arg1628Cys

p.R1628C

O75376

protein_coding

deleterious(0)

probably_damaging(0.99)

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

NCOR1

SNV

Missense_Mutation

c.3644N>G

p.Lys1215Arg

p.K1215R

O75376

protein_coding

deleterious(0.03)

probably_damaging(0.985)

TCGA-AR-A0TV-01

Breast

breast invasive carcinoma

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

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