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: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:0097193111	Esophagus	ESCC	intrinsic apoptotic signaling pathway	222/8552	288/18723	5.87e-28	2.02e-25	222
GO:004477216	Esophagus	ESCC	mitotic cell cycle phase transition	281/8552	424/18723	4.63e-18	4.45e-16	281
GO:000020917	Esophagus	ESCC	protein polyubiquitination	170/8552	236/18723	1.40e-16	1.09e-14	170
GO:007093617	Esophagus	ESCC	protein K48-linked ubiquitination	55/8552	65/18723	8.42e-11	2.58e-09	55
GO:00065136	Esophagus	ESCC	protein monoubiquitination	53/8552	67/18723	2.11e-08	4.03e-07	53
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:004586018	Esophagus	ESCC	positive regulation of protein kinase activity	219/8552	386/18723	6.91e-06	6.97e-05	219
GO:003367420	Esophagus	ESCC	positive regulation of kinase activity	260/8552	467/18723	7.26e-06	7.22e-05	260
GO:00311461	Esophagus	ESCC	SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	33/8552	49/18723	1.80e-03	8.26e-03	33
GO:00431617	Liver	NAFLD	proteasome-mediated ubiquitin-dependent protein catabolic process	91/1882	412/18723	3.00e-13	1.75e-10	91
GO:00104987	Liver	NAFLD	proteasomal protein catabolic process	101/1882	490/18723	1.35e-12	6.09e-10	101
GO:00002095	Liver	NAFLD	protein polyubiquitination	51/1882	236/18723	1.04e-07	8.10e-06	51
GO:00709364	Liver	NAFLD	protein K48-linked ubiquitination	19/1882	65/18723	1.33e-05	3.97e-04	19
GO:00458606	Liver	NAFLD	positive regulation of protein kinase activity	65/1882	386/18723	2.22e-05	6.13e-04	65
GO:00336747	Liver	NAFLD	positive regulation of kinase activity	74/1882	467/18723	5.16e-05	1.19e-03	74
GO:0044772	Liver	NAFLD	mitotic cell cycle phase transition	67/1882	424/18723	1.25e-04	2.39e-03	67
GO:0044843	Liver	NAFLD	cell cycle G1/S phase transition	43/1882	241/18723	1.40e-04	2.63e-03	43

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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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