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: FBXW7

Gene summary for FBXW7

Gene summary.

Gene information	Species	Human
	Gene symbol	FBXW7
	Gene ID	55294
	Gene name	F-box and WD repeat domain containing 7
	Gene Alias	AGO
	Cytomap	4q31.3
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	Q969H0

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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
55294	FBXW7	CA_HPV_3	Human	Cervix	CC	2.54e-02	1.82e-01	0.0414
55294	FBXW7	CCI_1	Human	Cervix	CC	4.43e-04	6.57e-01	0.528
55294	FBXW7	CCI_2	Human	Cervix	CC	8.95e-11	1.53e+00	0.5249
55294	FBXW7	CCI_3	Human	Cervix	CC	3.28e-11	9.81e-01	0.516
55294	FBXW7	HTA11_3410_2000001011	Human	Colorectum	AD	3.78e-28	-7.60e-01	0.0155
55294	FBXW7	HTA11_2487_2000001011	Human	Colorectum	SER	2.74e-09	-6.55e-01	-0.1808
55294	FBXW7	HTA11_2951_2000001011	Human	Colorectum	AD	7.54e-05	-9.10e-01	0.0216
55294	FBXW7	HTA11_78_2000001011	Human	Colorectum	AD	3.00e-09	-6.05e-01	-0.1088
55294	FBXW7	HTA11_3361_2000001011	Human	Colorectum	AD	1.65e-14	-7.83e-01	-0.1207
55294	FBXW7	HTA11_83_2000001011	Human	Colorectum	SER	7.73e-05	-5.49e-01	-0.1526
55294	FBXW7	HTA11_696_2000001011	Human	Colorectum	AD	7.75e-16	-5.82e-01	-0.1464
55294	FBXW7	HTA11_866_2000001011	Human	Colorectum	AD	6.12e-10	-4.95e-01	-0.1001
55294	FBXW7	HTA11_5212_2000001011	Human	Colorectum	AD	5.26e-07	-8.44e-01	-0.2061
55294	FBXW7	HTA11_5216_2000001011	Human	Colorectum	SER	6.88e-03	-5.64e-01	-0.1462
55294	FBXW7	HTA11_546_2000001011	Human	Colorectum	AD	4.08e-02	-5.72e-01	-0.0842
55294	FBXW7	HTA11_9341_2000001011	Human	Colorectum	SER	7.00e-03	-8.47e-01	-0.00410000000000005
55294	FBXW7	HTA11_7862_2000001011	Human	Colorectum	AD	5.03e-06	-7.14e-01	-0.0179
55294	FBXW7	HTA11_866_3004761011	Human	Colorectum	AD	5.35e-17	-6.97e-01	0.096
55294	FBXW7	HTA11_9408_2000001011	Human	Colorectum	AD	7.94e-03	-8.68e-01	0.0451
55294	FBXW7	HTA11_8622_2000001021	Human	Colorectum	SER	6.18e-07	-8.56e-01	0.0528

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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
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:00313988	Skin	AK	positive regulation of protein ubiquitination	21/1910	119/18723	8.77e-03	4.32e-02	21
GO:00456383	Skin	AK	negative regulation of myeloid cell differentiation	17/1910	90/18723	8.93e-03	4.39e-02	17
GO:190288224	Skin	AK	regulation of response to oxidative stress	18/1910	98/18723	9.72e-03	4.72e-02	18
GO:2001233112	Skin	SCCIS	regulation of apoptotic signaling pathway	51/919	356/18723	5.51e-12	7.43e-09	51
GO:0042176112	Skin	SCCIS	regulation of protein catabolic process	54/919	391/18723	5.60e-12	7.43e-09	54
GO:0097193112	Skin	SCCIS	intrinsic apoptotic signaling pathway	42/919	288/18723	2.40e-10	2.12e-07	42
GO:1903362112	Skin	SCCIS	regulation of cellular protein catabolic process	38/919	255/18723	9.24e-10	5.45e-07	38
GO:2001242112	Skin	SCCIS	regulation of intrinsic apoptotic signaling pathway	28/919	164/18723	7.32e-09	2.95e-06	28
GO:0045732112	Skin	SCCIS	positive regulation of protein catabolic process	34/919	231/18723	9.75e-09	3.45e-06	34
GO:1903364112	Skin	SCCIS	positive regulation of cellular protein catabolic process	26/919	155/18723	3.64e-08	7.72e-06	26
GO:1903050112	Skin	SCCIS	regulation of proteolysis involved in cellular protein catabolic process	32/919	221/18723	3.93e-08	7.72e-06	32
GO:000268318	Skin	SCCIS	negative regulation of immune system process	49/919	434/18723	4.92e-08	8.19e-06	49
GO:2000058112	Skin	SCCIS	regulation of ubiquitin-dependent protein catabolic process	26/919	164/18723	1.18e-07	1.52e-05	26
GO:0010631110	Skin	SCCIS	epithelial cell migration	42/919	357/18723	1.45e-07	1.74e-05	42
GO:0050673110	Skin	SCCIS	epithelial cell proliferation	48/919	437/18723	1.56e-07	1.84e-05	48
GO:0045862112	Skin	SCCIS	positive regulation of proteolysis	43/919	372/18723	1.69e-07	1.91e-05	43
GO:0090132110	Skin	SCCIS	epithelium migration	42/919	360/18723	1.82e-07	1.97e-05	42
GO:0090130110	Skin	SCCIS	tissue migration	42/919	365/18723	2.66e-07	2.62e-05	42
GO:1903320112	Skin	SCCIS	regulation of protein modification by small protein conjugation or removal	32/919	242/18723	3.31e-07	3.03e-05	32
GO:190210516	Skin	SCCIS	regulation of leukocyte differentiation	35/919	279/18723	3.43e-07	3.03e-05	35

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0412014	Cervix	CC	Ubiquitin mediated proteolysis	49/1267	142/8465	4.26e-09	7.68e-08	4.54e-08	49
hsa0412015	Cervix	CC	Ubiquitin mediated proteolysis	49/1267	142/8465	4.26e-09	7.68e-08	4.54e-08	49
hsa04120	Colorectum	AD	Ubiquitin mediated proteolysis	58/2092	142/8465	1.46e-05	1.53e-04	9.76e-05	58
hsa041201	Colorectum	AD	Ubiquitin mediated proteolysis	58/2092	142/8465	1.46e-05	1.53e-04	9.76e-05	58
hsa041202	Colorectum	SER	Ubiquitin mediated proteolysis	39/1580	142/8465	6.18e-03	3.66e-02	2.66e-02	39
hsa041203	Colorectum	SER	Ubiquitin mediated proteolysis	39/1580	142/8465	6.18e-03	3.66e-02	2.66e-02	39
hsa041204	Colorectum	MSS	Ubiquitin mediated proteolysis	55/1875	142/8465	5.02e-06	6.00e-05	3.68e-05	55
hsa041205	Colorectum	MSS	Ubiquitin mediated proteolysis	55/1875	142/8465	5.02e-06	6.00e-05	3.68e-05	55
hsa041206	Colorectum	FAP	Ubiquitin mediated proteolysis	51/1404	142/8465	1.55e-08	5.84e-07	3.55e-07	51
hsa041207	Colorectum	FAP	Ubiquitin mediated proteolysis	51/1404	142/8465	1.55e-08	5.84e-07	3.55e-07	51
hsa041208	Colorectum	CRC	Ubiquitin mediated proteolysis	42/1091	142/8465	9.98e-08	6.67e-06	4.52e-06	42
hsa041209	Colorectum	CRC	Ubiquitin mediated proteolysis	42/1091	142/8465	9.98e-08	6.67e-06	4.52e-06	42
hsa0412016	Endometrium	AEH	Ubiquitin mediated proteolysis	41/1197	142/8465	3.42e-06	4.27e-05	3.13e-05	41
hsa0412017	Endometrium	AEH	Ubiquitin mediated proteolysis	41/1197	142/8465	3.42e-06	4.27e-05	3.13e-05	41
hsa0412023	Endometrium	EEC	Ubiquitin mediated proteolysis	41/1237	142/8465	7.86e-06	9.58e-05	7.14e-05	41
hsa0412033	Endometrium	EEC	Ubiquitin mediated proteolysis	41/1237	142/8465	7.86e-06	9.58e-05	7.14e-05	41
hsa0412027	Esophagus	ESCC	Ubiquitin mediated proteolysis	122/4205	142/8465	6.53e-20	7.29e-18	3.74e-18	122
hsa0412036	Esophagus	ESCC	Ubiquitin mediated proteolysis	122/4205	142/8465	6.53e-20	7.29e-18	3.74e-18	122
hsa0412010	Liver	NAFLD	Ubiquitin mediated proteolysis	44/1043	142/8465	2.59e-09	1.70e-07	1.37e-07	44
hsa0412011	Liver	NAFLD	Ubiquitin mediated proteolysis	44/1043	142/8465	2.59e-09	1.70e-07	1.37e-07	44

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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

FBXW7

SNV

Missense_Mutation

c.529N>C

p.Glu177Gln

p.E177Q

Q969H0

protein_coding

deleterious_low_confidence(0.01)

benign(0.058)

TCGA-3C-AALI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Poly E

Complete Response

FBXW7

SNV

Missense_Mutation

rs866987936

c.1436G>A

p.Arg479Gln

p.R479Q

Q969H0

protein_coding

deleterious(0.03)

probably_damaging(1)

TCGA-A2-A0D0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

FBXW7

SNV

Missense_Mutation

c.529G>C

p.Glu177Gln

p.E177Q

Q969H0

protein_coding

deleterious_low_confidence(0.01)

benign(0.058)

TCGA-A2-A3XT-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

FBXW7

SNV

Missense_Mutation

c.1625N>T

p.Asn542Ile

p.N542I

Q969H0

protein_coding

deleterious(0)

probably_damaging(0.983)

TCGA-A7-A6VW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

FBXW7

SNV

Missense_Mutation

c.902N>C

p.Leu301Pro

p.L301P

Q969H0

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A8-A09M-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

paclitaxel

FBXW7

SNV

Missense_Mutation

novel

c.38N>T

p.Arg13Leu

p.R13L

Q969H0

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(0.931)

TCGA-AC-A2QI-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

cytoxan

FBXW7

SNV

Missense_Mutation

c.1634N>G

p.Tyr545Cys

p.Y545C

Q969H0

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AR-A256-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

FBXW7

SNV

Missense_Mutation

novel

c.1195G>C

p.Asp399His

p.D399H

Q969H0

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-BH-A2L8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

FBXW7

SNV

Missense_Mutation

c.529N>A

p.Glu177Lys

p.E177K

Q969H0

protein_coding

deleterious_low_confidence(0.01)

benign(0.021)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

FBXW7

SNV

Missense_Mutation

rs867384286

c.1393N>T

p.Arg465Cys

p.R465C

Q969H0

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-E2-A574-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

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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
55294	FBXW7	DNA REPAIR, CLINICALLY ACTIONABLE		Docetaxel	DOCETAXEL	23274910
55294	FBXW7	DNA REPAIR, CLINICALLY ACTIONABLE		Sirolimus	SIROLIMUS	24586741,18787170,23558291
55294	FBXW7	DNA REPAIR, CLINICALLY ACTIONABLE		Vorinostat	VORINOSTAT	23274910
55294	FBXW7	DNA REPAIR, CLINICALLY ACTIONABLE		AR-42	AR-42	23274910
55294	FBXW7	DNA REPAIR, CLINICALLY ACTIONABLE		Regorafenib	REGORAFENIB	27399335
55294	FBXW7	DNA REPAIR, CLINICALLY ACTIONABLE		Temsirolimus	TEMSIROLIMUS	24360397
55294	FBXW7	DNA REPAIR, CLINICALLY ACTIONABLE		Entinostat	ENTINOSTAT	23274910
55294	FBXW7	DNA REPAIR, CLINICALLY ACTIONABLE		SIROLIMUS	SIROLIMUS	18787170
55294	FBXW7	DNA REPAIR, CLINICALLY ACTIONABLE		Belinostat	BELINOSTAT	23274910
55294	FBXW7	DNA REPAIR, CLINICALLY ACTIONABLE		MRK-003		17646409

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