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: FBXW8

Gene summary for FBXW8

Gene summary.

Gene information	Species	Human
	Gene symbol	FBXW8
	Gene ID	26259
	Gene name	F-box and WD repeat domain containing 8
	Gene Alias	FBW6
	Cytomap	12q24.22
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	Q8N3Y1

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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
26259	FBXW8	HTA11_3410_2000001011	Human	Colorectum	AD	7.95e-10	-4.36e-01	0.0155
26259	FBXW8	HTA11_2487_2000001011	Human	Colorectum	SER	2.57e-02	-3.74e-01	-0.1808
26259	FBXW8	HTA11_78_2000001011	Human	Colorectum	AD	1.27e-02	-3.56e-01	-0.1088
26259	FBXW8	HTA11_3361_2000001011	Human	Colorectum	AD	3.25e-02	-3.97e-01	-0.1207
26259	FBXW8	HTA11_7862_2000001011	Human	Colorectum	AD	3.78e-03	-5.12e-01	-0.0179
26259	FBXW8	HTA11_99999970781_79442	Human	Colorectum	MSS	1.09e-06	-3.47e-01	0.294
26259	FBXW8	HTA11_99999974143_84620	Human	Colorectum	MSS	6.09e-04	-3.13e-01	0.3005
26259	FBXW8	A001-C-207	Human	Colorectum	FAP	4.71e-05	-3.32e-01	0.1278
26259	FBXW8	A015-C-203	Human	Colorectum	FAP	8.59e-23	-4.32e-01	-0.1294
26259	FBXW8	A015-C-204	Human	Colorectum	FAP	5.35e-04	-2.15e-01	-0.0228
26259	FBXW8	A014-C-040	Human	Colorectum	FAP	8.06e-04	-3.98e-01	-0.1184
26259	FBXW8	A002-C-201	Human	Colorectum	FAP	2.58e-13	-3.52e-01	0.0324
26259	FBXW8	A002-C-203	Human	Colorectum	FAP	4.14e-02	-1.47e-01	0.2786
26259	FBXW8	A001-C-119	Human	Colorectum	FAP	3.24e-07	-3.64e-01	-0.1557
26259	FBXW8	A001-C-108	Human	Colorectum	FAP	1.65e-10	-2.77e-01	-0.0272
26259	FBXW8	A002-C-205	Human	Colorectum	FAP	2.00e-17	-3.98e-01	-0.1236
26259	FBXW8	A015-C-006	Human	Colorectum	FAP	1.42e-08	-2.55e-01	-0.0994
26259	FBXW8	A015-C-106	Human	Colorectum	FAP	5.31e-03	-1.68e-01	-0.0511
26259	FBXW8	A002-C-114	Human	Colorectum	FAP	7.04e-14	-3.59e-01	-0.1561
26259	FBXW8	A015-C-104	Human	Colorectum	FAP	5.06e-20	-3.17e-01	-0.1899

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:19033641	Colorectum	SER	positive regulation of cellular protein catabolic process	56/2897	155/18723	2.09e-10	2.85e-08	56
GO:20000581	Colorectum	SER	regulation of ubiquitin-dependent protein catabolic process	57/2897	164/18723	7.98e-10	8.74e-08	57
GO:00313311	Colorectum	SER	positive regulation of cellular catabolic process	114/2897	427/18723	1.22e-09	1.27e-07	114
GO:00611361	Colorectum	SER	regulation of proteasomal protein catabolic process	62/2897	187/18723	1.28e-09	1.31e-07	62
GO:00226041	Colorectum	SER	regulation of cell morphogenesis	89/2897	309/18723	1.51e-09	1.52e-07	89
GO:19030521	Colorectum	SER	positive regulation of proteolysis involved in cellular protein catabolic process	47/2897	133/18723	1.30e-08	1.02e-06	47
GO:20000601	Colorectum	SER	positive regulation of ubiquitin-dependent protein catabolic process	40/2897	107/18723	2.57e-08	1.79e-06	40
GO:00431611	Colorectum	SER	proteasome-mediated ubiquitin-dependent protein catabolic process	105/2897	412/18723	7.48e-08	4.70e-06	105
GO:00324341	Colorectum	SER	regulation of proteasomal ubiquitin-dependent protein catabolic process	45/2897	134/18723	1.48e-07	8.67e-06	45
GO:19018001	Colorectum	SER	positive regulation of proteasomal protein catabolic process	38/2897	114/18723	1.65e-06	7.23e-05	38
GO:00324361	Colorectum	SER	positive regulation of proteasomal ubiquitin-dependent protein catabolic process	32/2897	90/18723	2.23e-06	9.31e-05	32
GO:00018901	Colorectum	SER	placenta development	43/2897	144/18723	9.10e-06	3.03e-04	43
GO:00018921	Colorectum	SER	embryonic placenta development	28/2897	82/18723	2.24e-05	6.43e-04	28
GO:00107691	Colorectum	SER	regulation of cell morphogenesis involved in differentiation	31/2897	96/18723	2.95e-05	7.89e-04	31
GO:00107701	Colorectum	SER	positive regulation of cell morphogenesis involved in differentiation	26/2897	79/18723	8.81e-05	1.91e-03	26
GO:00163581	Colorectum	SER	dendrite development	58/2897	243/18723	3.82e-04	5.81e-03	58
GO:00607111	Colorectum	SER	labyrinthine layer development	16/2897	44/18723	5.64e-04	7.83e-03	16
GO:00107201	Colorectum	SER	positive regulation of cell development	66/2897	298/18723	1.36e-03	1.50e-02	66
GO:00109751	Colorectum	SER	regulation of neuron projection development	92/2897	445/18723	1.85e-03	1.89e-02	92
GO:00313461	Colorectum	SER	positive regulation of cell projection organization	75/2897	353/18723	2.22e-03	2.14e-02	75

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
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

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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

FBXW8

SNV

Missense_Mutation

rs368052577

c.1670N>A

p.Arg557His

p.R557H

Q8N3Y1

protein_coding

tolerated(0.6)

benign(0.003)

TCGA-A2-A0D0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

FBXW8

SNV

Missense_Mutation

c.1148N>T

p.Ala383Val

p.A383V

Q8N3Y1

protein_coding

tolerated(1)

benign(0)

TCGA-A8-A0A7-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

FBXW8

SNV

Missense_Mutation

rs779200230

c.364N>A

p.Glu122Lys

p.E122K

Q8N3Y1

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

FBXW8

SNV

Missense_Mutation

rs753804526

c.592N>T

p.Arg198Cys

p.R198C

Q8N3Y1

protein_coding

deleterious(0)

probably_damaging(0.968)

TCGA-E2-A1LB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

FBXW8

SNV

Missense_Mutation

c.1175N>C

p.Asp392Ala

p.D392A

Q8N3Y1

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-E9-A295-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

FBXW8

SNV

Missense_Mutation

rs773598560

c.1626N>G

p.Asp542Glu

p.D542E

Q8N3Y1

protein_coding

tolerated(0.53)

benign(0.055)

TCGA-EW-A1PD-01

Breast

breast invasive carcinoma

Male

<65

I/II

Chemotherapy

docetaxel

FBXW8

SNV

Missense_Mutation

c.1174N>A

p.Asp392Asn

p.D392N

Q8N3Y1

protein_coding

deleterious(0.01)

probably_damaging(0.996)

TCGA-C5-A1BM-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

FBXW8

SNV

Missense_Mutation

novel

c.1064G>C

p.Arg355Thr

p.R355T

Q8N3Y1

protein_coding

tolerated(0.68)

benign(0.001)

TCGA-EA-A3HU-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

FBXW8

SNV

Missense_Mutation

rs868211841

c.1588G>A

p.Ala530Thr

p.A530T

Q8N3Y1

protein_coding

deleterious(0)

possibly_damaging(0.904)

TCGA-EA-A50E-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

FBXW8

SNV

Missense_Mutation

rs758915610

c.713N>A

p.Arg238His

p.R238H

Q8N3Y1

protein_coding

tolerated(0.07)

benign(0.241)

TCGA-A6-2686-01

Colorectum

colon adenocarcinoma

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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