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: CUL4B

Gene summary for CUL4B

Gene summary.

Gene information	Species	Human
	Gene symbol	CUL4B
	Gene ID	8450
	Gene name	cullin 4B
	Gene Alias	CUL-4B
	Cytomap	Xq24
	Gene Type	protein-coding
	GO ID	GO:0000082
	UniProtAcc	Q13620

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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
8450	CUL4B	LZE7T	Human	Esophagus	ESCC	1.24e-02	3.29e-01	0.0667
8450	CUL4B	LZE22T	Human	Esophagus	ESCC	7.26e-07	3.39e-01	0.068
8450	CUL4B	LZE24T	Human	Esophagus	ESCC	3.74e-09	3.08e-01	0.0596
8450	CUL4B	P2T-E	Human	Esophagus	ESCC	5.13e-16	2.33e-01	0.1177
8450	CUL4B	P4T-E	Human	Esophagus	ESCC	3.86e-10	1.21e-01	0.1323
8450	CUL4B	P5T-E	Human	Esophagus	ESCC	3.41e-03	1.57e-02	0.1327
8450	CUL4B	P8T-E	Human	Esophagus	ESCC	3.12e-17	9.52e-02	0.0889
8450	CUL4B	P9T-E	Human	Esophagus	ESCC	4.58e-09	1.39e-01	0.1131
8450	CUL4B	P10T-E	Human	Esophagus	ESCC	1.33e-21	3.17e-01	0.116
8450	CUL4B	P11T-E	Human	Esophagus	ESCC	3.72e-07	1.93e-01	0.1426
8450	CUL4B	P12T-E	Human	Esophagus	ESCC	7.67e-17	3.76e-02	0.1122
8450	CUL4B	P15T-E	Human	Esophagus	ESCC	7.77e-11	1.07e-01	0.1149
8450	CUL4B	P16T-E	Human	Esophagus	ESCC	2.08e-10	3.12e-02	0.1153
8450	CUL4B	P17T-E	Human	Esophagus	ESCC	3.73e-07	2.72e-01	0.1278
8450	CUL4B	P20T-E	Human	Esophagus	ESCC	8.84e-05	3.89e-02	0.1124
8450	CUL4B	P21T-E	Human	Esophagus	ESCC	1.96e-20	1.94e-01	0.1617
8450	CUL4B	P22T-E	Human	Esophagus	ESCC	2.34e-08	1.44e-01	0.1236
8450	CUL4B	P23T-E	Human	Esophagus	ESCC	2.67e-03	1.20e-01	0.108
8450	CUL4B	P24T-E	Human	Esophagus	ESCC	6.44e-03	7.12e-02	0.1287
8450	CUL4B	P26T-E	Human	Esophagus	ESCC	2.05e-15	2.56e-01	0.1276

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:0022613111	Esophagus	ESCC	ribonucleoprotein complex biogenesis	365/8552	463/18723	1.74e-49	1.11e-45	365
GO:0042254111	Esophagus	ESCC	ribosome biogenesis	252/8552	299/18723	3.27e-44	1.04e-40	252
GO:0010498111	Esophagus	ESCC	proteasomal protein catabolic process	369/8552	490/18723	1.13e-41	1.80e-38	369
GO:0043161111	Esophagus	ESCC	proteasome-mediated ubiquitin-dependent protein catabolic process	312/8552	412/18723	3.53e-36	4.48e-33	312
GO:001657015	Esophagus	ESCC	histone modification	323/8552	463/18723	2.61e-26	7.88e-24	323
GO:004477216	Esophagus	ESCC	mitotic cell cycle phase transition	281/8552	424/18723	4.63e-18	4.45e-16	281
GO:000941113	Esophagus	ESCC	response to UV	115/8552	149/18723	3.29e-15	1.93e-13	115
GO:000931419	Esophagus	ESCC	response to radiation	277/8552	456/18723	4.42e-11	1.43e-09	277
GO:003464413	Esophagus	ESCC	cellular response to UV	70/8552	90/18723	4.59e-10	1.20e-08	70
GO:007121419	Esophagus	ESCC	cellular response to abiotic stimulus	206/8552	331/18723	7.52e-10	1.88e-08	206
GO:010400419	Esophagus	ESCC	cellular response to environmental stimulus	206/8552	331/18723	7.52e-10	1.88e-08	206
GO:00065136	Esophagus	ESCC	protein monoubiquitination	53/8552	67/18723	2.11e-08	4.03e-07	53
GO:001657414	Esophagus	ESCC	histone ubiquitination	40/8552	47/18723	2.40e-08	4.55e-07	40
GO:007147816	Esophagus	ESCC	cellular response to radiation	122/8552	186/18723	3.07e-08	5.73e-07	122
GO:000008214	Esophagus	ESCC	G1/S transition of mitotic cell cycle	134/8552	214/18723	4.04e-07	5.55e-06	134
GO:004484314	Esophagus	ESCC	cell cycle G1/S phase transition	148/8552	241/18723	5.68e-07	7.48e-06	148
GO:003352213	Esophagus	ESCC	histone H2A ubiquitination	23/8552	26/18723	6.82e-06	6.90e-05	23
GO:00103904	Esophagus	ESCC	histone monoubiquitination	25/8552	29/18723	7.24e-06	7.20e-05	25
GO:000941611	Esophagus	ESCC	response to light stimulus	183/8552	320/18723	2.03e-05	1.76e-04	183
GO:00355182	Esophagus	ESCC	histone H2A monoubiquitination	15/8552	17/18723	3.48e-04	2.03e-03	15

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0412027	Esophagus	ESCC	Ubiquitin mediated proteolysis	122/4205	142/8465	6.53e-20	7.29e-18	3.74e-18	122
hsa0342022	Esophagus	ESCC	Nucleotide excision repair	54/4205	63/8465	2.01e-09	2.17e-08	1.11e-08	54
hsa05170210	Esophagus	ESCC	Human immunodeficiency virus 1 infection	147/4205	212/8465	3.37e-09	3.53e-08	1.81e-08	147
hsa0412036	Esophagus	ESCC	Ubiquitin mediated proteolysis	122/4205	142/8465	6.53e-20	7.29e-18	3.74e-18	122
hsa0342032	Esophagus	ESCC	Nucleotide excision repair	54/4205	63/8465	2.01e-09	2.17e-08	1.11e-08	54
hsa0517038	Esophagus	ESCC	Human immunodeficiency virus 1 infection	147/4205	212/8465	3.37e-09	3.53e-08	1.81e-08	147
hsa0412041	Liver	HCC	Ubiquitin mediated proteolysis	110/4020	142/8465	1.67e-13	3.74e-12	2.08e-12	110
hsa051709	Liver	HCC	Human immunodeficiency virus 1 infection	125/4020	212/8465	4.51e-04	1.94e-03	1.08e-03	125
hsa034202	Liver	HCC	Nucleotide excision repair	41/4020	63/8465	3.59e-03	1.12e-02	6.22e-03	41
hsa0412051	Liver	HCC	Ubiquitin mediated proteolysis	110/4020	142/8465	1.67e-13	3.74e-12	2.08e-12	110
hsa0517012	Liver	HCC	Human immunodeficiency virus 1 infection	125/4020	212/8465	4.51e-04	1.94e-03	1.08e-03	125
hsa034203	Liver	HCC	Nucleotide excision repair	41/4020	63/8465	3.59e-03	1.12e-02	6.22e-03	41
hsa0412020	Oral cavity	OSCC	Ubiquitin mediated proteolysis	105/3704	142/8465	1.83e-13	4.37e-12	2.23e-12	105
hsa0517027	Oral cavity	OSCC	Human immunodeficiency virus 1 infection	133/3704	212/8465	1.42e-08	1.40e-07	7.12e-08	133
hsa034204	Oral cavity	OSCC	Nucleotide excision repair	49/3704	63/8465	3.48e-08	2.91e-07	1.48e-07	49
hsa04120110	Oral cavity	OSCC	Ubiquitin mediated proteolysis	105/3704	142/8465	1.83e-13	4.37e-12	2.23e-12	105
hsa05170111	Oral cavity	OSCC	Human immunodeficiency virus 1 infection	133/3704	212/8465	1.42e-08	1.40e-07	7.12e-08	133
hsa0342011	Oral cavity	OSCC	Nucleotide excision repair	49/3704	63/8465	3.48e-08	2.91e-07	1.48e-07	49
hsa0412024	Prostate	Tumor	Ubiquitin mediated proteolysis	61/1791	142/8465	3.08e-09	5.09e-08	3.16e-08	61
hsa0517026	Prostate	Tumor	Human immunodeficiency virus 1 infection	62/1791	212/8465	3.05e-03	1.12e-02	6.94e-03	62

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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

CUL4B

SNV

Missense_Mutation

rs750144966

c.1003N>T

p.His335Tyr

p.H335Y

Q13620

protein_coding

tolerated(0.23)

benign(0.013)

TCGA-A2-A0YK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

CUL4B

SNV

Missense_Mutation

novel

c.413C>G

p.Ser138Cys

p.S138C

Q13620

protein_coding

deleterious(0.01)

benign(0.443)

TCGA-A8-A06R-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

5-fluorouracil

CUL4B

SNV

Missense_Mutation

c.2683N>A

p.Asp895Asn

p.D895N

Q13620

protein_coding

deleterious(0)

probably_damaging(0.986)

TCGA-A8-A09G-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

CUL4B

SNV

Missense_Mutation

c.643N>A

p.Glu215Lys

p.E215K

Q13620

protein_coding

tolerated(0.31)

benign(0.009)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CUL4B

SNV

Missense_Mutation

c.1106G>A

p.Arg369Gln

p.R369Q

Q13620

protein_coding

tolerated(0.15)

benign(0.116)

TCGA-AN-A049-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CUL4B

SNV

Missense_Mutation

novel

c.1811A>G

p.Glu604Gly

p.E604G

Q13620

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AO-A1KO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

paclitaxel

CUL4B

SNV

Missense_Mutation

c.2569A>G

p.Ile857Val

p.I857V

Q13620

protein_coding

tolerated(0.11)

possibly_damaging(0.811)

TCGA-B6-A0RL-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CUL4B

SNV

Missense_Mutation

novel

c.1876G>A

p.Glu626Lys

p.E626K

Q13620

protein_coding

deleterious(0.01)

probably_damaging(1)

TCGA-BH-A2L8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

CUL4B

SNV

Missense_Mutation

novel

c.962N>C

p.Leu321Pro

p.L321P

Q13620

protein_coding

deleterious(0.02)

probably_damaging(0.979)

TCGA-E2-A14T-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

CUL4B

SNV

Missense_Mutation

novel

c.2557G>A

p.Ala853Thr

p.A853T

Q13620

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-E2-A2P5-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

arimidex

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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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