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: FGFR2

Gene summary for FGFR2

Gene summary.

Gene information	Species	Human
	Gene symbol	FGFR2
	Gene ID	2263
	Gene name	fibroblast growth factor receptor 2
	Gene Alias	BBDS
	Cytomap	10q26.13
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	P21802

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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
2263	FGFR2	CA_HPV_1	Human	Cervix	CC	8.51e-05	-1.49e-01	0.0264
2263	FGFR2	CA_HPV_3	Human	Cervix	CC	1.97e-23	4.50e-01	0.0414
2263	FGFR2	CCI_1	Human	Cervix	CC	6.18e-03	6.82e-01	0.528
2263	FGFR2	CCI_2	Human	Cervix	CC	1.04e-03	6.95e-01	0.5249
2263	FGFR2	CCI_3	Human	Cervix	CC	2.01e-02	5.07e-01	0.516
2263	FGFR2	HTA11_1938_2000001011	Human	Colorectum	AD	2.06e-04	4.09e-01	-0.0811
2263	FGFR2	HTA11_78_2000001011	Human	Colorectum	AD	2.15e-10	7.37e-01	-0.1088
2263	FGFR2	HTA11_83_2000001011	Human	Colorectum	SER	1.90e-02	5.56e-01	-0.1526
2263	FGFR2	HTA11_866_2000001011	Human	Colorectum	AD	8.09e-11	5.73e-01	-0.1001
2263	FGFR2	HTA11_1391_2000001011	Human	Colorectum	AD	2.04e-03	4.46e-01	-0.059
2263	FGFR2	HTA11_546_2000001011	Human	Colorectum	AD	6.24e-03	5.32e-01	-0.0842
2263	FGFR2	A008-E-015	Human	Colorectum	FAP	1.76e-02	2.45e-01	0.0177
2263	FGFR2	CRC-1-8810	Human	Colorectum	CRC	2.86e-02	-1.80e-01	0.6257
2263	FGFR2	AEH-subject1	Human	Endometrium	AEH	1.28e-05	3.41e-01	-0.3059
2263	FGFR2	AEH-subject3	Human	Endometrium	AEH	2.22e-08	3.63e-01	-0.2576
2263	FGFR2	AEH-subject5	Human	Endometrium	AEH	2.41e-14	5.35e-01	-0.2953
2263	FGFR2	EEC-subject1	Human	Endometrium	EEC	2.50e-13	5.55e-01	-0.2682
2263	FGFR2	EEC-subject2	Human	Endometrium	EEC	1.22e-25	6.67e-01	-0.2607
2263	FGFR2	EEC-subject5	Human	Endometrium	EEC	1.43e-05	2.79e-01	-0.249
2263	FGFR2	GSM6177620_NYU_UCEC1_lib1_lib1	Human	Endometrium	EEC	4.88e-11	2.52e-01	-0.1869

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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
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:004206010	Cervix	CC	wound healing	109/2311	422/18723	1.84e-14	1.57e-11	109
GO:00085446	Cervix	CC	epidermis development	83/2311	324/18723	3.91e-11	8.54e-09	83
GO:00435884	Cervix	CC	skin development	71/2311	263/18723	8.04e-11	1.46e-08	71
GO:00506737	Cervix	CC	epithelial cell proliferation	98/2311	437/18723	2.01e-09	2.15e-07	98
GO:00160557	Cervix	CC	Wnt signaling pathway	98/2311	444/18723	4.82e-09	4.65e-07	98
GO:01987387	Cervix	CC	cell-cell signaling by wnt	98/2311	446/18723	6.16e-09	5.58e-07	98
GO:003367410	Cervix	CC	positive regulation of kinase activity	101/2311	467/18723	8.66e-09	7.22e-07	101
GO:00301117	Cervix	CC	regulation of Wnt signaling pathway	76/2311	328/18723	3.05e-08	2.08e-06	76
GO:00506787	Cervix	CC	regulation of epithelial cell proliferation	83/2311	381/18723	1.31e-07	6.42e-06	83
GO:00018908	Cervix	CC	placenta development	40/2311	144/18723	4.59e-07	1.77e-05	40
GO:00022379	Cervix	CC	response to molecule of bacterial origin	78/2311	363/18723	5.55e-07	2.06e-05	78
GO:00324969	Cervix	CC	response to lipopolysaccharide	74/2311	343/18723	9.15e-07	3.25e-05	74
GO:00614588	Cervix	CC	reproductive system development	87/2311	427/18723	1.37e-06	4.55e-05	87
GO:00608287	Cervix	CC	regulation of canonical Wnt signaling pathway	58/2311	253/18723	1.83e-06	5.89e-05	58
GO:00486088	Cervix	CC	reproductive structure development	86/2311	424/18723	1.90e-06	5.97e-05	86
GO:00600707	Cervix	CC	canonical Wnt signaling pathway	66/2311	303/18723	2.47e-06	7.35e-05	66
GO:00457876	Cervix	CC	positive regulation of cell cycle	66/2311	313/18723	7.78e-06	1.81e-04	66
GO:00615647	Cervix	CC	axon development	89/2311	467/18723	1.71e-05	3.27e-04	89
GO:004873210	Cervix	CC	gland development	84/2311	436/18723	1.93e-05	3.54e-04	84
GO:00309019	Cervix	CC	midbrain development	26/2311	90/18723	2.12e-05	3.82e-04	26

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0414424	Endometrium	EEC	Endocytosis	57/1237	251/8465	3.34e-04	2.82e-03	2.10e-03	57
hsa0401522	Endometrium	EEC	Rap1 signaling pathway	49/1237	210/8465	4.45e-04	3.47e-03	2.59e-03	49
hsa0521522	Endometrium	EEC	Prostate cancer	25/1237	97/8465	2.66e-03	1.56e-02	1.16e-02	25
hsa0481024	Endometrium	EEC	Regulation of actin cytoskeleton	49/1237	229/8465	3.20e-03	1.78e-02	1.33e-02	49
hsa0414434	Endometrium	EEC	Endocytosis	57/1237	251/8465	3.34e-04	2.82e-03	2.10e-03	57
hsa0401532	Endometrium	EEC	Rap1 signaling pathway	49/1237	210/8465	4.45e-04	3.47e-03	2.59e-03	49
hsa0521532	Endometrium	EEC	Prostate cancer	25/1237	97/8465	2.66e-03	1.56e-02	1.16e-02	25
hsa0481034	Endometrium	EEC	Regulation of actin cytoskeleton	49/1237	229/8465	3.20e-03	1.78e-02	1.33e-02	49
hsa04144210	Esophagus	ESCC	Endocytosis	186/4205	251/8465	9.74e-16	4.66e-14	2.39e-14	186
hsa0521516	Esophagus	ESCC	Prostate cancer	72/4205	97/8465	6.12e-07	4.10e-06	2.10e-06	72
hsa0523018	Esophagus	ESCC	Central carbon metabolism in cancer	50/4205	70/8465	1.70e-04	6.62e-04	3.39e-04	50
hsa0152110	Esophagus	ESCC	EGFR tyrosine kinase inhibitor resistance	55/4205	79/8465	2.44e-04	8.78e-04	4.50e-04	55
hsa0481028	Esophagus	ESCC	Regulation of actin cytoskeleton	133/4205	229/8465	5.94e-03	1.48e-02	7.56e-03	133
hsa041517	Esophagus	ESCC	PI3K-Akt signaling pathway	197/4205	354/8465	1.24e-02	2.83e-02	1.45e-02	197
hsa0414437	Esophagus	ESCC	Endocytosis	186/4205	251/8465	9.74e-16	4.66e-14	2.39e-14	186
hsa0521517	Esophagus	ESCC	Prostate cancer	72/4205	97/8465	6.12e-07	4.10e-06	2.10e-06	72
hsa0523019	Esophagus	ESCC	Central carbon metabolism in cancer	50/4205	70/8465	1.70e-04	6.62e-04	3.39e-04	50
hsa0152115	Esophagus	ESCC	EGFR tyrosine kinase inhibitor resistance	55/4205	79/8465	2.44e-04	8.78e-04	4.50e-04	55
hsa04810112	Esophagus	ESCC	Regulation of actin cytoskeleton	133/4205	229/8465	5.94e-03	1.48e-02	7.56e-03	133
hsa0415114	Esophagus	ESCC	PI3K-Akt signaling pathway	197/4205	354/8465	1.24e-02	2.83e-02	1.45e-02	197

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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
FGF7	FGFR2	FGF7_FGFR2	FGF	Cervix	ADJ
FGF1	FGFR2	FGF1_FGFR2	FGF	Cervix	CC
FGF7	FGFR2	FGF7_FGFR2	FGF	Cervix	CC
FGF2	FGFR2	FGF2_FGFR2	FGF	CRC	ADJ
FGF7	FGFR2	FGF7_FGFR2	FGF	CRC	CRC
FGF2	FGFR2	FGF2_FGFR2	FGF	Endometrium	ADJ
FGF2	FGFR2	FGF2_FGFR2	FGF	Endometrium	AEH
FGF2	FGFR2	FGF2_FGFR2	FGF	Endometrium	EEC
FGF7	FGFR2	FGF7_FGFR2	FGF	Endometrium	EEC
FGF1	FGFR2	FGF1_FGFR2	FGF	HNSCC	OSCC
FGF2	FGFR2	FGF2_FGFR2	FGF	HNSCC	OSCC
FGF7	FGFR2	FGF7_FGFR2	FGF	HNSCC	OSCC
FGF18	FGFR2	FGF18_FGFR2	FGF	HNSCC	OSCC
FGF2	FGFR2	FGF2_FGFR2	FGF	HNSCC	Precancer
FGF7	FGFR2	FGF7_FGFR2	FGF	HNSCC	Precancer
FGF7	FGFR2	FGF7_FGFR2	FGF	Lung	AAH
FGF7	FGFR2	FGF7_FGFR2	FGF	Lung	ADJ
FGF7	FGFR2	FGF7_FGFR2	FGF	Lung	AIS
FGF7	FGFR2	FGF7_FGFR2	FGF	Lung	IAC
FGF7	FGFR2	FGF7_FGFR2	FGF	Lung	Precancer

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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

FGFR2

SNV

Missense_Mutation

rs779423644

c.364G>A

p.Val122Met

p.V122M

P21802

protein_coding

deleterious(0.01)

possibly_damaging(0.902)

TCGA-3C-AALJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

FGFR2

SNV

Missense_Mutation

c.338N>C

p.Val113Ala

p.V113A

P21802

protein_coding

tolerated(0.52)

benign(0.1)

TCGA-A8-A09D-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

FGFR2

SNV

Missense_Mutation

c.1763N>G

p.Ser588Cys

p.S588C

P21802

protein_coding

tolerated(0.31)

possibly_damaging(0.857)

TCGA-A8-A09X-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

FGFR2

SNV

Missense_Mutation

c.785N>C

p.Leu262Pro

p.L262P

P21802

protein_coding

deleterious(0.01)

probably_damaging(0.937)

TCGA-AN-A03X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

FGFR2

SNV

Missense_Mutation

novel

c.1904N>C

p.Val635Ala

p.V635A

P21802

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

FGFR2

SNV

Missense_Mutation

rs121913474

c.1147T>C

p.Cys383Arg

p.C383R

P21802

protein_coding

deleterious(0.02)

possibly_damaging(0.865)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

FGFR2

SNV

Missense_Mutation

c.1650T>G

p.Asn550Lys

p.N550K

P21802

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AN-A0FL-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

FGFR2

SNV

Missense_Mutation

c.1099N>C

p.Glu367Gln

p.E367Q

P21802

protein_coding

tolerated(0.19)

benign(0.156)

TCGA-D8-A1JA-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

FGFR2

SNV

Missense_Mutation

rs121913476

c.1650T>A

p.Asn550Lys

p.N550K

P21802

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-D8-A1XL-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide+tamoxifen

FGFR2

SNV

Missense_Mutation

c.1414G>T

p.Asp472Tyr

p.D472Y

P21802

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-E2-A14W-01

Breast

breast invasive carcinoma

Male

>=65

I/II

Chemotherapy

cytoxan

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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
2263	FGFR2	KINASE, DRUGGABLE GENOME, TYROSINE KINASE, CLINICALLY ACTIONABLE, CELL SURFACE		AZ6089		22869148
2263	FGFR2	KINASE, DRUGGABLE GENOME, TYROSINE KINASE, CLINICALLY ACTIONABLE, CELL SURFACE		CVBT-141H
2263	FGFR2	KINASE, DRUGGABLE GENOME, TYROSINE KINASE, CLINICALLY ACTIONABLE, CELL SURFACE	inhibitor	BGJ398	INFIGRATINIB
2263	FGFR2	KINASE, DRUGGABLE GENOME, TYROSINE KINASE, CLINICALLY ACTIONABLE, CELL SURFACE		DOVITINIB	DOVITINIB
2263	FGFR2	KINASE, DRUGGABLE GENOME, TYROSINE KINASE, CLINICALLY ACTIONABLE, CELL SURFACE	inhibitor	252827519
2263	FGFR2	KINASE, DRUGGABLE GENOME, TYROSINE KINASE, CLINICALLY ACTIONABLE, CELL SURFACE		TRAFERMIN	TRAFERMIN
2263	FGFR2	KINASE, DRUGGABLE GENOME, TYROSINE KINASE, CLINICALLY ACTIONABLE, CELL SURFACE	inhibitor	NINTEDANIB	NINTEDANIB
2263	FGFR2	KINASE, DRUGGABLE GENOME, TYROSINE KINASE, CLINICALLY ACTIONABLE, CELL SURFACE		Trametinib	TRAMETINIB	27338794
2263	FGFR2	KINASE, DRUGGABLE GENOME, TYROSINE KINASE, CLINICALLY ACTIONABLE, CELL SURFACE	inhibitor	CHEMBL1852688	INFIGRATINIB
2263	FGFR2	KINASE, DRUGGABLE GENOME, TYROSINE KINASE, CLINICALLY ACTIONABLE, CELL SURFACE	inhibitor	LENVATINIB	LENVATINIB

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