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: CUL1

Gene summary for CUL1

Gene summary.

Gene information	Species	Human
	Gene symbol	CUL1
	Gene ID	8454
	Gene name	cullin 1
	Gene Alias	CUL1
	Cytomap	7q36.1
	Gene Type	protein-coding
	GO ID	GO:0000082
	UniProtAcc	A0A090N7U0

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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
8454	CUL1	LZE4T	Human	Esophagus	ESCC	1.87e-05	2.48e-01	0.0811
8454	CUL1	LZE7T	Human	Esophagus	ESCC	3.74e-08	5.14e-01	0.0667
8454	CUL1	LZE8T	Human	Esophagus	ESCC	3.02e-06	2.73e-01	0.067
8454	CUL1	LZE20T	Human	Esophagus	ESCC	6.67e-05	1.18e-01	0.0662
8454	CUL1	LZE22T	Human	Esophagus	ESCC	9.04e-04	3.58e-01	0.068
8454	CUL1	LZE24T	Human	Esophagus	ESCC	9.36e-09	3.58e-01	0.0596
8454	CUL1	LZE21T	Human	Esophagus	ESCC	1.12e-02	1.67e-01	0.0655
8454	CUL1	P1T-E	Human	Esophagus	ESCC	2.27e-09	3.63e-01	0.0875
8454	CUL1	P2T-E	Human	Esophagus	ESCC	3.99e-21	2.80e-01	0.1177
8454	CUL1	P4T-E	Human	Esophagus	ESCC	1.46e-18	5.45e-01	0.1323
8454	CUL1	P5T-E	Human	Esophagus	ESCC	1.99e-23	5.05e-01	0.1327
8454	CUL1	P8T-E	Human	Esophagus	ESCC	1.42e-12	2.78e-01	0.0889
8454	CUL1	P9T-E	Human	Esophagus	ESCC	4.19e-14	4.10e-01	0.1131
8454	CUL1	P10T-E	Human	Esophagus	ESCC	8.04e-21	4.44e-01	0.116
8454	CUL1	P11T-E	Human	Esophagus	ESCC	7.99e-10	3.21e-01	0.1426
8454	CUL1	P12T-E	Human	Esophagus	ESCC	1.40e-37	8.44e-01	0.1122
8454	CUL1	P15T-E	Human	Esophagus	ESCC	5.62e-35	8.87e-01	0.1149
8454	CUL1	P16T-E	Human	Esophagus	ESCC	1.47e-22	5.21e-01	0.1153
8454	CUL1	P17T-E	Human	Esophagus	ESCC	2.02e-03	2.41e-01	0.1278
8454	CUL1	P19T-E	Human	Esophagus	ESCC	1.80e-09	4.91e-01	0.1662

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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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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:00448435	Prostate	BPH	cell cycle G1/S phase transition	68/3107	241/18723	3.80e-06	5.83e-05	68
GO:00000825	Prostate	BPH	G1/S transition of mitotic cell cycle	62/3107	214/18723	3.93e-06	5.97e-05	62
GO:00709368	Prostate	BPH	protein K48-linked ubiquitination	26/3107	65/18723	5.90e-06	8.64e-05	26
GO:00002099	Prostate	BPH	protein polyubiquitination	64/3107	236/18723	2.83e-05	3.31e-04	64
GO:00065134	Prostate	BPH	protein monoubiquitination	20/3107	67/18723	4.93e-03	2.33e-02	20
GO:009719319	Prostate	Tumor	intrinsic apoptotic signaling pathway	113/3246	288/18723	6.79e-19	2.64e-16	113
GO:001049819	Prostate	Tumor	proteasomal protein catabolic process	158/3246	490/18723	3.05e-16	6.76e-14	158
GO:004316119	Prostate	Tumor	proteasome-mediated ubiquitin-dependent protein catabolic process	130/3246	412/18723	7.97e-13	8.00e-11	130
GO:003367417	Prostate	Tumor	positive regulation of kinase activity	123/3246	467/18723	5.36e-07	1.15e-05	123
GO:004586015	Prostate	Tumor	positive regulation of protein kinase activity	105/3246	386/18723	7.09e-07	1.43e-05	105
GO:007093615	Prostate	Tumor	protein K48-linked ubiquitination	26/3246	65/18723	1.33e-05	1.83e-04	26
GO:000008212	Prostate	Tumor	G1/S transition of mitotic cell cycle	62/3246	214/18723	1.63e-05	2.18e-04	62
GO:004484312	Prostate	Tumor	cell cycle G1/S phase transition	67/3246	241/18723	3.28e-05	3.88e-04	67
GO:004477214	Prostate	Tumor	mitotic cell cycle phase transition	106/3246	424/18723	3.61e-05	4.21e-04	106
GO:000020914	Prostate	Tumor	protein polyubiquitination	64/3246	236/18723	1.08e-04	1.03e-03	64
GO:000651312	Prostate	Tumor	protein monoubiquitination	21/3246	67/18723	3.61e-03	1.86e-02	21
GO:009719328	Skin	AK	intrinsic apoptotic signaling pathway	82/1910	288/18723	2.01e-18	2.97e-15	82
GO:001049827	Skin	AK	proteasomal protein catabolic process	97/1910	490/18723	9.65e-11	1.54e-08	97
GO:004316127	Skin	AK	proteasome-mediated ubiquitin-dependent protein catabolic process	84/1910	412/18723	3.96e-10	4.88e-08	84
GO:004477210	Skin	AK	mitotic cell cycle phase transition	83/1910	424/18723	3.81e-09	3.05e-07	83

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa04141211	Esophagus	ESCC	Protein processing in endoplasmic reticulum	147/4205	174/8465	3.29e-22	1.10e-19	5.64e-20	147
hsa0412027	Esophagus	ESCC	Ubiquitin mediated proteolysis	122/4205	142/8465	6.53e-20	7.29e-18	3.74e-18	122
hsa0411023	Esophagus	ESCC	Cell cycle	126/4205	157/8465	1.34e-15	5.60e-14	2.87e-14	126
hsa05131211	Esophagus	ESCC	Shigellosis	176/4205	247/8465	2.27e-12	4.01e-11	2.05e-11	176
hsa05170210	Esophagus	ESCC	Human immunodeficiency virus 1 infection	147/4205	212/8465	3.37e-09	3.53e-08	1.81e-08	147
hsa043507	Esophagus	ESCC	TGF-beta signaling pathway	69/4205	108/8465	1.92e-03	5.54e-03	2.84e-03	69
hsa047105	Esophagus	ESCC	Circadian rhythm	24/4205	34/8465	1.09e-02	2.51e-02	1.29e-02	24
hsa041146	Esophagus	ESCC	Oocyte meiosis	77/4205	131/8465	2.19e-02	4.80e-02	2.46e-02	77
hsa04141310	Esophagus	ESCC	Protein processing in endoplasmic reticulum	147/4205	174/8465	3.29e-22	1.10e-19	5.64e-20	147
hsa0412036	Esophagus	ESCC	Ubiquitin mediated proteolysis	122/4205	142/8465	6.53e-20	7.29e-18	3.74e-18	122
hsa0411033	Esophagus	ESCC	Cell cycle	126/4205	157/8465	1.34e-15	5.60e-14	2.87e-14	126
hsa05131310	Esophagus	ESCC	Shigellosis	176/4205	247/8465	2.27e-12	4.01e-11	2.05e-11	176
hsa0517038	Esophagus	ESCC	Human immunodeficiency virus 1 infection	147/4205	212/8465	3.37e-09	3.53e-08	1.81e-08	147
hsa0435014	Esophagus	ESCC	TGF-beta signaling pathway	69/4205	108/8465	1.92e-03	5.54e-03	2.84e-03	69
hsa0471012	Esophagus	ESCC	Circadian rhythm	24/4205	34/8465	1.09e-02	2.51e-02	1.29e-02	24
hsa0411411	Esophagus	ESCC	Oocyte meiosis	77/4205	131/8465	2.19e-02	4.80e-02	2.46e-02	77
hsa0412010	Liver	NAFLD	Ubiquitin mediated proteolysis	44/1043	142/8465	2.59e-09	1.70e-07	1.37e-07	44
hsa0513114	Liver	NAFLD	Shigellosis	48/1043	247/8465	7.82e-04	1.17e-02	9.39e-03	48
hsa0412011	Liver	NAFLD	Ubiquitin mediated proteolysis	44/1043	142/8465	2.59e-09	1.70e-07	1.37e-07	44
hsa0513115	Liver	NAFLD	Shigellosis	48/1043	247/8465	7.82e-04	1.17e-02	9.39e-03	48

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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

CUL1

SNV

Missense_Mutation

novel

c.1711N>C

p.Ala571Pro

p.A571P

Q13616

protein_coding

tolerated(0.27)

benign(0.39)

TCGA-A2-A0SV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Other, specify in notesBisphosphonate therapy

zometa

CUL1

SNV

Missense_Mutation

novel

c.1181N>G

p.Ala394Gly

p.A394G

Q13616

protein_coding

deleterious(0.01)

probably_damaging(0.917)

TCGA-A2-A1G4-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

adriamycin

CUL1

SNV

Missense_Mutation

novel

c.1555G>A

p.Glu519Lys

p.E519K

Q13616

protein_coding

tolerated(0.24)

possibly_damaging(0.514)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CUL1

SNV

Missense_Mutation

c.721G>C

p.Glu241Gln

p.E241Q

Q13616

protein_coding

deleterious(0.02)

possibly_damaging(0.762)

TCGA-AQ-A0Y5-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

cytoxan

CUL1

SNV

Missense_Mutation

novel

c.1660N>T

p.Ala554Ser

p.A554S

Q13616

protein_coding

tolerated(1)

benign(0.001)

TCGA-AR-A24Q-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

CUL1

SNV

Missense_Mutation

novel

c.1118N>C

p.Val373Ala

p.V373A

Q13616

protein_coding

deleterious(0.03)

probably_damaging(0.942)

TCGA-BH-A0HA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CUL1

SNV

Missense_Mutation

novel

c.1181C>G

p.Ala394Gly

p.A394G

Q13616

protein_coding

deleterious(0.01)

probably_damaging(0.917)

TCGA-BH-A0HU-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

docetaxel

CUL1

SNV

Missense_Mutation

c.1549N>G

p.Leu517Val

p.L517V

Q13616

protein_coding

deleterious(0)

probably_damaging(0.947)

TCGA-BH-A0RX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

fluorouracil

CUL1

SNV

Missense_Mutation

c.436C>T

p.Arg146Cys

p.R146C

Q13616

protein_coding

deleterious(0)

benign(0.063)

TCGA-E2-A1AZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

CUL1

SNV

Missense_Mutation

novel

c.2110G>C

p.Glu704Gln

p.E704Q

Q13616

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-PL-A8LV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

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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