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: FAT1

Gene summary for FAT1

Gene summary.

Gene information	Species	Human
	Gene symbol	FAT1
	Gene ID	2195
	Gene name	FAT atypical cadherin 1
	Gene Alias	CDHF7
	Cytomap	4q35.2
	Gene Type	protein-coding
	GO ID	GO:0000902
	UniProtAcc	Q14517

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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
2195	FAT1	CA_HPV_1	Human	Cervix	CC	5.98e-15	-3.11e-01	0.0264
2195	FAT1	CCI_3	Human	Cervix	CC	1.19e-05	8.23e-01	0.516
2195	FAT1	T1	Human	Cervix	CC	8.35e-04	3.31e-01	0.0918
2195	FAT1	HTA11_3410_2000001011	Human	Colorectum	AD	2.57e-15	-5.42e-01	0.0155
2195	FAT1	HTA11_3361_2000001011	Human	Colorectum	AD	2.35e-03	-5.50e-01	-0.1207
2195	FAT1	HTA11_99999971662_82457	Human	Colorectum	MSS	5.36e-03	5.78e-01	0.3859
2195	FAT1	HTA11_99999974143_84620	Human	Colorectum	MSS	1.39e-03	-3.73e-01	0.3005
2195	FAT1	F007	Human	Colorectum	FAP	1.81e-03	1.49e-01	0.1176
2195	FAT1	A002-C-010	Human	Colorectum	FAP	6.29e-03	3.65e-02	0.242
2195	FAT1	A001-C-207	Human	Colorectum	FAP	1.14e-04	4.28e-02	0.1278
2195	FAT1	A015-C-203	Human	Colorectum	FAP	1.38e-32	-4.57e-02	-0.1294
2195	FAT1	A015-C-204	Human	Colorectum	FAP	1.72e-06	-1.83e-01	-0.0228
2195	FAT1	A014-C-040	Human	Colorectum	FAP	1.94e-05	-7.64e-02	-0.1184
2195	FAT1	A002-C-201	Human	Colorectum	FAP	5.22e-16	-3.65e-02	0.0324
2195	FAT1	A002-C-203	Human	Colorectum	FAP	1.89e-02	-2.00e-02	0.2786
2195	FAT1	A001-C-119	Human	Colorectum	FAP	3.69e-07	-2.78e-02	-0.1557
2195	FAT1	A001-C-108	Human	Colorectum	FAP	5.20e-20	2.08e-01	-0.0272
2195	FAT1	A002-C-021	Human	Colorectum	FAP	3.10e-02	3.32e-01	0.1171
2195	FAT1	A002-C-205	Human	Colorectum	FAP	4.87e-33	2.56e-01	-0.1236
2195	FAT1	A001-C-104	Human	Colorectum	FAP	2.64e-07	2.02e-01	0.0184

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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
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
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:00350891	Prostate	Tumor	establishment of apical/basal cell polarity	9/3246	22/18723	7.96e-03	3.52e-02	9
GO:00016541	Prostate	Tumor	eye development	82/3246	371/18723	1.02e-02	4.27e-02	82
GO:000716326	Skin	AK	establishment or maintenance of cell polarity	53/1910	218/18723	1.32e-09	1.26e-07	53
GO:000701528	Skin	AK	actin filament organization	85/1910	442/18723	5.94e-09	4.14e-07	85
GO:000206425	Skin	AK	epithelial cell development	51/1910	220/18723	1.50e-08	9.13e-07	51
GO:003001019	Skin	AK	establishment of cell polarity	36/1910	143/18723	2.24e-07	9.02e-06	36
GO:00017388	Skin	AK	morphogenesis of a polarized epithelium	22/1910	94/18723	1.55e-04	1.84e-03	22
GO:00350889	Skin	AK	establishment or maintenance of apical/basal cell polarity	14/1910	49/18723	2.72e-04	2.89e-03	14
GO:00612459	Skin	AK	establishment or maintenance of bipolar cell polarity	14/1910	49/18723	2.72e-04	2.89e-03	14
GO:00451979	Skin	AK	establishment or maintenance of epithelial cell apical/basal polarity	11/1910	44/18723	3.87e-03	2.29e-02	11
GO:00033825	Skin	AK	epithelial cell morphogenesis	9/1910	33/18723	4.68e-03	2.69e-02	9
GO:0007163110	Skin	SCCIS	establishment or maintenance of cell polarity	31/919	218/18723	9.72e-08	1.29e-05	31
GO:0002064111	Skin	SCCIS	epithelial cell development	29/919	220/18723	1.25e-06	8.07e-05	29
GO:0030010110	Skin	SCCIS	establishment of cell polarity	20/919	143/18723	2.28e-05	6.50e-04	20
GO:0007015111	Skin	SCCIS	actin filament organization	40/919	442/18723	1.50e-04	3.04e-03	40
GO:00987421	Skin	SCCIS	cell-cell adhesion via plasma-membrane adhesion molecules	26/919	273/18723	9.83e-04	1.23e-02	26
GO:000173813	Skin	SCCIS	morphogenesis of a polarized epithelium	12/919	94/18723	2.13e-03	2.17e-02	12
GO:000338212	Skin	SCCIS	epithelial cell morphogenesis	6/919	33/18723	4.88e-03	3.99e-02	6
GO:000716327	Skin	cSCC	establishment or maintenance of cell polarity	103/4864	218/18723	9.44e-12	4.85e-10	103
GO:003001025	Skin	cSCC	establishment of cell polarity	65/4864	143/18723	3.60e-07	7.18e-06	65

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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

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

FAT1

SNV

Missense_Mutation

c.7117N>A

p.Asp2373Asn

p.D2373N

Q14517

protein_coding

deleterious(0)

possibly_damaging(0.715)

TCGA-A2-A0CX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

FAT1

SNV

Missense_Mutation

c.3131A>G

p.Lys1044Arg

p.K1044R

Q14517

protein_coding

tolerated(0.15)

benign(0.052)

TCGA-A2-A0D0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

FAT1

SNV

Missense_Mutation

c.6226G>A

p.Asp2076Asn

p.D2076N

Q14517

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-A7-A0CE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

FAT1

SNV

Missense_Mutation

rs200357548

c.10478N>T

p.Pro3493Leu

p.P3493L

Q14517

protein_coding

deleterious(0.02)

benign(0.081)

TCGA-A8-A08T-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

FAT1

SNV

Missense_Mutation

novel

c.404T>C

p.Val135Ala

p.V135A

Q14517

protein_coding

deleterious(0)

benign(0.345)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

FAT1

SNV

Missense_Mutation

c.6179N>T

p.Ser2060Phe

p.S2060F

Q14517

protein_coding

tolerated(0.57)

possibly_damaging(0.748)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

FAT1

SNV

Missense_Mutation

novel

c.6445G>A

p.Glu2149Lys

p.E2149K

Q14517

protein_coding

deleterious(0.03)

benign(0.243)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

FAT1

SNV

Missense_Mutation

rs772458580

c.1654G>A

p.Glu552Lys

p.E552K

Q14517

protein_coding

deleterious(0.02)

possibly_damaging(0.685)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

FAT1

SNV

Missense_Mutation

c.9619N>G

p.Pro3207Ala

p.P3207A

Q14517

protein_coding

tolerated(0.06)

probably_damaging(0.999)

TCGA-AN-A0FV-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

FAT1

SNV

Missense_Mutation

rs371394820

c.5284N>A

p.Ala1762Thr

p.A1762T

Q14517

protein_coding

tolerated(0.22)

benign(0.022)

TCGA-AQ-A1H2-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

herceptin

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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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