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: FOXP1

Gene summary for FOXP1

Gene summary.

Gene information	Species	Human
	Gene symbol	FOXP1
	Gene ID	27086
	Gene name	forkhead box P1
	Gene Alias	12CC4
	Cytomap	3p13
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	Q9H334

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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
27086	FOXP1	GSM4909286	Human	Breast	IDC	1.99e-04	8.58e-02	0.1081
27086	FOXP1	GSM4909290	Human	Breast	IDC	6.29e-06	4.22e-01	0.2096
27086	FOXP1	GSM4909293	Human	Breast	IDC	6.65e-14	4.31e-01	0.1581
27086	FOXP1	GSM4909297	Human	Breast	IDC	1.95e-05	1.86e-01	0.1517
27086	FOXP1	GSM4909298	Human	Breast	IDC	2.29e-33	6.16e-01	0.1551
27086	FOXP1	GSM4909299	Human	Breast	IDC	1.93e-06	3.27e-01	0.035
27086	FOXP1	GSM4909301	Human	Breast	IDC	3.51e-27	6.96e-01	0.1577
27086	FOXP1	GSM4909309	Human	Breast	IDC	2.58e-02	2.50e-01	0.0483
27086	FOXP1	GSM4909311	Human	Breast	IDC	6.34e-14	-4.15e-02	0.1534
27086	FOXP1	GSM4909313	Human	Breast	IDC	2.19e-07	3.62e-01	0.0391
27086	FOXP1	GSM4909317	Human	Breast	IDC	3.46e-02	2.98e-01	0.1355
27086	FOXP1	GSM4909319	Human	Breast	IDC	2.30e-17	-2.30e-01	0.1563
27086	FOXP1	GSM4909320	Human	Breast	IDC	4.15e-05	1.06e-01	0.1575
27086	FOXP1	GSM4909321	Human	Breast	IDC	1.35e-06	8.99e-02	0.1559
27086	FOXP1	brca1	Human	Breast	Precancer	1.18e-02	-2.95e-01	-0.0338
27086	FOXP1	M1	Human	Breast	IDC	2.17e-06	4.47e-01	0.1577
27086	FOXP1	NCCBC14	Human	Breast	DCIS	7.98e-08	-6.33e-02	0.2021
27086	FOXP1	NCCBC5	Human	Breast	DCIS	1.88e-09	-2.61e-01	0.2046
27086	FOXP1	P1	Human	Breast	IDC	1.26e-12	2.50e-02	0.1527
27086	FOXP1	P2	Human	Breast	IDC	4.38e-06	2.64e-01	0.21

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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
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:00485459	Breast	Precancer	response to steroid hormone	53/1080	339/18723	3.07e-11	3.66e-09	53
GO:00300999	Breast	Precancer	myeloid cell differentiation	45/1080	381/18723	4.00e-06	1.25e-04	45
GO:00018196	Breast	Precancer	positive regulation of cytokine production	52/1080	467/18723	4.18e-06	1.29e-04	52
GO:00022378	Breast	Precancer	response to molecule of bacterial origin	43/1080	363/18723	6.05e-06	1.72e-04	43
GO:00324968	Breast	Precancer	response to lipopolysaccharide	41/1080	343/18723	7.94e-06	2.17e-04	41
GO:0050727	Breast	Precancer	regulation of inflammatory response	44/1080	386/18723	1.26e-05	3.22e-04	44
GO:00421107	Breast	Precancer	T cell activation	52/1080	487/18723	1.37e-05	3.42e-04	52
GO:00713838	Breast	Precancer	cellular response to steroid hormone stimulus	28/1080	204/18723	1.78e-05	4.26e-04	28
GO:00106348	Breast	Precancer	positive regulation of epithelial cell migration	25/1080	176/18723	2.75e-05	6.21e-04	25
GO:00456379	Breast	Precancer	regulation of myeloid cell differentiation	28/1080	210/18723	3.05e-05	6.72e-04	28
GO:19037069	Breast	Precancer	regulation of hemopoiesis	41/1080	367/18723	3.95e-05	8.52e-04	41
GO:00106319	Breast	Precancer	epithelial cell migration	40/1080	357/18723	4.57e-05	9.71e-04	40
GO:00901329	Breast	Precancer	epithelium migration	40/1080	360/18723	5.51e-05	1.14e-03	40
GO:00025737	Breast	Precancer	myeloid leukocyte differentiation	27/1080	208/18723	6.72e-05	1.35e-03	27
GO:00435426	Breast	Precancer	endothelial cell migration	33/1080	279/18723	7.28e-05	1.44e-03	33
GO:00901309	Breast	Precancer	tissue migration	40/1080	365/18723	7.48e-05	1.47e-03	40
GO:00105953	Breast	Precancer	positive regulation of endothelial cell migration	20/1080	133/18723	7.59e-05	1.48e-03	20
GO:00302248	Breast	Precancer	monocyte differentiation	9/1080	36/18723	1.56e-04	2.66e-03	9
GO:00305217	Breast	Precancer	androgen receptor signaling pathway	10/1080	44/18723	1.61e-04	2.69e-03	10
GO:19021055	Breast	Precancer	regulation of leukocyte differentiation	32/1080	279/18723	1.66e-04	2.74e-03	32

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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
FOXP1	INCAF	Breast	DCIS	NNMT,COL6A3,MT-CO3, etc.	9.41e-02
FOXP1	ECM	Breast	DCIS	NNMT,COL6A3,MT-CO3, etc.	4.53e-01
FOXP1	INCAF	Breast	IDC	NNMT,COL6A3,MT-CO3, etc.	5.45e-01
FOXP1	IMGOB	Colorectum	MSI-H	GMDS,MCTP2,FRYL, etc.	2.57e-01
FOXP1	STM	Colorectum	MSS	GMDS,MCTP2,FRYL, etc.	2.64e-01
FOXP1	IMGOB	Colorectum	MSS	GMDS,MCTP2,FRYL, etc.	2.90e-02
FOXP1	MYOFIB	Colorectum	Healthy	PDZRN3,MYLK,ARHGEF3, etc.	6.57e-01
FOXP1	CILIA	Endometrium	EEC	PDGFD,SHANK2,ZBTB20, etc.	1.95e-01
FOXP1	BMEM	Endometrium	ADJ	BCL11B,CAMK4,SARAF, etc.	1.39e-01
FOXP1	CD8TEXP	Endometrium	Healthy	BCL11B,CAMK4,SARAF, etc.	1.62e-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

FOXP1

SNV

Missense_Mutation

rs797045585

c.1510N>G

p.Arg504Gly

p.R504G

protein_coding

deleterious(0.02)

probably_damaging(0.999)

TCGA-BH-A1F8-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

FOXP1

SNV

Missense_Mutation

c.1323N>G

p.Asp441Glu

p.D441E

protein_coding

tolerated(0.24)

benign(0.015)

TCGA-C8-A12L-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

FOXP1

deletion

Frame_Shift_Del

novel

c.679_680delNN

p.Glu227ThrfsTer67

p.E227Tfs*67

protein_coding

TCGA-A2-A4RY-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

taxotere

FOXP1

insertion

Nonsense_Mutation

novel

c.1964_1965insTACTTTTTGTTGAAAAAAGGAATTTGTACTCTGTGCATT

p.Pro655_Leu656insThrPheCysTerLysLysGluPheValLeuCysAlaPhe

p.P655_L656insTFC*KKEFVLCAF

protein_coding

TCGA-A8-A09E-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozole

FOXP1

insertion

Nonsense_Mutation

novel

c.198_199insACAGCTCTGGAGGATGAAATACGACTATGTTGACCTTT

p.Gln67ThrfsTer11

p.Q67Tfs*11

protein_coding

TCGA-A8-A09E-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozole

FOXP1

insertion

Frame_Shift_Ins

novel

c.706_707insGTGA

p.Thr236SerfsTer60

p.T236Sfs*60

protein_coding

TCGA-AC-A3YJ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

FOXP1

deletion

Frame_Shift_Del

novel

c.328delN

p.Gln110SerfsTer12

p.Q110Sfs*12

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

FOXP1

SNV

Missense_Mutation

novel

c.1306C>T

p.Arg436Cys

p.R436C

protein_coding

deleterious(0)

probably_damaging(0.987)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

FOXP1

SNV

Missense_Mutation

c.1091C>T

p.Ala364Val

p.A364V

protein_coding

deleterious(0.03)

possibly_damaging(0.87)

TCGA-IR-A3LK-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

FOXP1

SNV

Missense_Mutation

c.1235N>T

p.Ala412Val

p.A412V

protein_coding

deleterious(0.02)

benign(0.225)

TCGA-MA-AA41-01

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

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