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: NCOA1

Gene summary for NCOA1

Gene summary.

Gene information	Species	Human
	Gene symbol	NCOA1
	Gene ID	8648
	Gene name	nuclear receptor coactivator 1
	Gene Alias	F-SRC-1
	Cytomap	2p23.3
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	Q15788

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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
8648	NCOA1	CA_HPV_1	Human	Cervix	CC	6.60e-04	-7.10e-02	0.0264
8648	NCOA1	CCI_1	Human	Cervix	CC	1.37e-03	1.11e+00	0.528
8648	NCOA1	CCI_2	Human	Cervix	CC	1.81e-08	1.15e+00	0.5249
8648	NCOA1	CCI_3	Human	Cervix	CC	2.64e-06	7.74e-01	0.516
8648	NCOA1	HTA11_3410_2000001011	Human	Colorectum	AD	3.79e-23	-7.54e-01	0.0155
8648	NCOA1	HTA11_2487_2000001011	Human	Colorectum	SER	1.24e-02	-3.28e-01	-0.1808
8648	NCOA1	HTA11_347_2000001011	Human	Colorectum	AD	2.45e-06	4.56e-01	-0.1954
8648	NCOA1	HTA11_3361_2000001011	Human	Colorectum	AD	7.81e-05	-5.63e-01	-0.1207
8648	NCOA1	HTA11_866_3004761011	Human	Colorectum	AD	2.65e-05	-5.19e-01	0.096
8648	NCOA1	HTA11_10711_2000001011	Human	Colorectum	AD	3.20e-06	-5.72e-01	0.0338
8648	NCOA1	HTA11_7696_3000711011	Human	Colorectum	AD	1.03e-17	-5.80e-01	0.0674
8648	NCOA1	HTA11_6818_2000001021	Human	Colorectum	AD	1.54e-06	-5.72e-01	0.0588
8648	NCOA1	HTA11_99999970781_79442	Human	Colorectum	MSS	4.05e-16	-5.33e-01	0.294
8648	NCOA1	HTA11_99999965062_69753	Human	Colorectum	MSI-H	3.87e-04	7.00e-01	0.3487
8648	NCOA1	HTA11_99999971662_82457	Human	Colorectum	MSS	7.79e-05	-3.96e-01	0.3859
8648	NCOA1	HTA11_99999973899_84307	Human	Colorectum	MSS	7.39e-04	-5.90e-01	0.2585
8648	NCOA1	HTA11_99999974143_84620	Human	Colorectum	MSS	7.97e-08	-4.19e-01	0.3005
8648	NCOA1	F007	Human	Colorectum	FAP	1.39e-02	-3.96e-01	0.1176
8648	NCOA1	A002-C-010	Human	Colorectum	FAP	4.58e-06	-2.58e-01	0.242
8648	NCOA1	A001-C-207	Human	Colorectum	FAP	1.21e-02	-3.38e-01	0.1278

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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:007149610	Cervix	CC	cellular response to external stimulus	78/2311	320/18723	1.82e-09	1.98e-07	78
GO:00316689	Cervix	CC	cellular response to extracellular stimulus	59/2311	246/18723	3.03e-07	1.24e-05	59
GO:00018908	Cervix	CC	placenta development	40/2311	144/18723	4.59e-07	1.77e-05	40
GO:004854510	Cervix	CC	response to steroid hormone	74/2311	339/18723	5.71e-07	2.09e-05	74
GO:00614588	Cervix	CC	reproductive system development	87/2311	427/18723	1.37e-06	4.55e-05	87
GO:00305229	Cervix	CC	intracellular receptor signaling pathway	60/2311	265/18723	1.89e-06	5.97e-05	60
GO:00486088	Cervix	CC	reproductive structure development	86/2311	424/18723	1.90e-06	5.97e-05	86
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:003166710	Cervix	CC	response to nutrient levels	92/2311	474/18723	5.80e-06	1.42e-04	92
GO:00316698	Cervix	CC	cellular response to nutrient levels	49/2311	215/18723	1.32e-05	2.68e-04	49
GO:190165410	Cervix	CC	response to ketone	45/2311	194/18723	1.83e-05	3.44e-04	45
GO:004873210	Cervix	CC	gland development	84/2311	436/18723	1.93e-05	3.54e-04	84
GO:00017018	Cervix	CC	in utero embryonic development	71/2311	367/18723	7.21e-05	1.00e-03	71
GO:00323556	Cervix	CC	response to estradiol	34/2311	141/18723	8.19e-05	1.11e-03	34
GO:00165705	Cervix	CC	histone modification	84/2311	463/18723	1.70e-04	2.01e-03	84
GO:00018928	Cervix	CC	embryonic placenta development	22/2311	82/18723	2.89e-04	3.12e-03	22
GO:00325704	Cervix	CC	response to progesterone	13/2311	37/18723	2.99e-04	3.21e-03	13
GO:00448492	Cervix	CC	estrous cycle	7/2311	16/18723	1.79e-03	1.34e-02	7
GO:00094109	Cervix	CC	response to xenobiotic stimulus	78/2311	462/18723	2.39e-03	1.70e-02	78

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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
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
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
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
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
hsa049199	Colorectum	FAP	Thyroid hormone signaling pathway	41/1404	121/8465	2.28e-06	4.28e-05	2.60e-05	41

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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

NCOA1

SNV

Missense_Mutation

c.2923N>A

p.Pro975Thr

p.P975T

Q15788

protein_coding

tolerated(0.06)

possibly_damaging(0.766)

TCGA-A2-A0YJ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

NCOA1

SNV

Missense_Mutation

novel

c.3535N>C

p.Thr1179Pro

p.T1179P

Q15788

protein_coding

tolerated(0.2)

benign(0.269)

TCGA-A2-A1FW-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

NCOA1

SNV

Missense_Mutation

c.258N>C

p.Glu86Asp

p.E86D

Q15788

protein_coding

tolerated(0.43)

benign(0.105)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NCOA1

SNV

Missense_Mutation

novel

c.1729N>A

p.Pro577Thr

p.P577T

Q15788

protein_coding

tolerated(0.08)

probably_damaging(0.941)

TCGA-AN-A03X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NCOA1

SNV

Missense_Mutation

c.483N>A

p.His161Gln

p.H161Q

Q15788

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AN-A0XO-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

NCOA1

SNV

Missense_Mutation

novel

c.1256A>C

p.Asn419Thr

p.N419T

Q15788

protein_coding

tolerated(0.14)

benign(0.201)

TCGA-B6-A0I5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

NCOA1

SNV

Missense_Mutation

c.4321G>A

p.Glu1441Lys

p.E1441K

Q15788

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.978)

TCGA-C8-A27B-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

NCOA1

SNV

Missense_Mutation

c.3938N>G

p.Asn1313Ser

p.N1313S

Q15788

protein_coding

tolerated(0.2)

possibly_damaging(0.86)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

NCOA1

SNV

Missense_Mutation

novel

c.2646N>T

p.Gln882His

p.Q882H

Q15788

protein_coding

deleterious(0.05)

possibly_damaging(0.601)

TCGA-OL-A5D8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

NCOA1

insertion

Nonsense_Mutation

novel

c.1730_1731insTTAAATTATTTGTATTAGGGAGACAAGGGAAG

p.Ala578Ter

p.A578*

Q15788

protein_coding

TCGA-AN-A03X-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
8648	NCOA1	ENZYME, CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR, NUCLEAR HORMONE RECEPTOR, TRANSCRIPTION FACTOR COMPLEX		TCMDC-123764	CHEMBL533226
8648	NCOA1	ENZYME, CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR, NUCLEAR HORMONE RECEPTOR, TRANSCRIPTION FACTOR COMPLEX		ETOPOSIDE	ETOPOSIDE
8648	NCOA1	ENZYME, CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR, NUCLEAR HORMONE RECEPTOR, TRANSCRIPTION FACTOR COMPLEX	inhibitor	252827441
8648	NCOA1	ENZYME, CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR, NUCLEAR HORMONE RECEPTOR, TRANSCRIPTION FACTOR COMPLEX		METHYLTHIONINIUM CHLORIDE	METHYLTHIONINIUM CHLORIDE
8648	NCOA1	ENZYME, CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR, NUCLEAR HORMONE RECEPTOR, TRANSCRIPTION FACTOR COMPLEX		tamoxifen	TAMOXIFEN	22174377

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