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: CUX1

Gene summary for CUX1

Gene summary.

Gene information	Species	Human
	Gene symbol	CUX1
	Gene ID	1523
	Gene name	cut like homeobox 1
	Gene Alias	CASP
	Cytomap	7q22.1
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	P39880

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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
1523	CUX1	CA_HPV_1	Human	Cervix	CC	3.73e-03	-3.18e-02	0.0264
1523	CUX1	CCI_1	Human	Cervix	CC	2.35e-16	1.91e+00	0.528
1523	CUX1	CCI_2	Human	Cervix	CC	1.72e-02	5.81e-01	0.5249
1523	CUX1	CCI_3	Human	Cervix	CC	2.99e-09	1.12e+00	0.516
1523	CUX1	L1	Human	Cervix	CC	5.35e-03	-3.24e-01	0.0802
1523	CUX1	HTA11_1938_2000001011	Human	Colorectum	AD	8.25e-12	7.34e-01	-0.0811
1523	CUX1	HTA11_347_2000001011	Human	Colorectum	AD	4.25e-28	1.00e+00	-0.1954
1523	CUX1	HTA11_411_2000001011	Human	Colorectum	SER	1.59e-08	1.02e+00	-0.2602
1523	CUX1	HTA11_3361_2000001011	Human	Colorectum	AD	4.92e-02	3.98e-01	-0.1207
1523	CUX1	HTA11_83_2000001011	Human	Colorectum	SER	7.43e-04	4.78e-01	-0.1526
1523	CUX1	HTA11_696_2000001011	Human	Colorectum	AD	1.18e-24	1.14e+00	-0.1464
1523	CUX1	HTA11_866_2000001011	Human	Colorectum	AD	4.95e-18	9.27e-01	-0.1001
1523	CUX1	HTA11_1391_2000001011	Human	Colorectum	AD	2.07e-14	1.15e+00	-0.059
1523	CUX1	HTA11_546_2000001011	Human	Colorectum	AD	4.41e-13	9.66e-01	-0.0842
1523	CUX1	HTA11_10623_2000001011	Human	Colorectum	AD	1.41e-02	5.46e-01	-0.0177
1523	CUX1	HTA11_7696_3000711011	Human	Colorectum	AD	1.31e-03	5.44e-01	0.0674
1523	CUX1	HTA11_6818_2000001011	Human	Colorectum	AD	5.81e-13	9.57e-01	0.0112
1523	CUX1	HTA11_11156_2000001011	Human	Colorectum	AD	1.61e-05	6.51e-01	0.0397
1523	CUX1	HTA11_99999965062_69753	Human	Colorectum	MSI-H	1.00e-05	7.47e-01	0.3487
1523	CUX1	HTA11_99999965104_69814	Human	Colorectum	MSS	4.82e-19	1.13e+00	0.281

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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
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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:00068914	Esophagus	ESCC	intra-Golgi vesicle-mediated transport	26/8552	33/18723	1.06e-04	7.43e-04	26
GO:001097516	Esophagus	ESCC	regulation of neuron projection development	240/8552	445/18723	2.48e-04	1.53e-03	240
GO:001076920	Esophagus	ESCC	regulation of cell morphogenesis involved in differentiation	61/8552	96/18723	3.12e-04	1.85e-03	61
GO:00519606	Esophagus	ESCC	regulation of nervous system development	237/8552	443/18723	5.02e-04	2.78e-03	237
GO:001077018	Esophagus	ESCC	positive regulation of cell morphogenesis involved in differentiation	51/8552	79/18723	5.48e-04	3.00e-03	51
GO:00519625	Esophagus	ESCC	positive regulation of nervous system development	149/8552	272/18723	1.50e-03	7.06e-03	149
GO:001635816	Esophagus	ESCC	dendrite development	130/8552	243/18723	8.33e-03	2.95e-02	130
GO:00481936	Liver	NAFLD	Golgi vesicle transport	66/1882	296/18723	3.66e-10	9.30e-08	66
GO:00226047	Liver	NAFLD	regulation of cell morphogenesis	62/1882	309/18723	8.35e-08	7.09e-06	62
GO:00107697	Liver	NAFLD	regulation of cell morphogenesis involved in differentiation	24/1882	96/18723	1.98e-05	5.62e-04	24
GO:00163585	Liver	NAFLD	dendrite development	43/1882	243/18723	1.70e-04	3.07e-03	43
GO:00313465	Liver	NAFLD	positive regulation of cell projection organization	57/1882	353/18723	2.19e-04	3.73e-03	57
GO:00107707	Liver	NAFLD	positive regulation of cell morphogenesis involved in differentiation	19/1882	79/18723	2.42e-04	4.06e-03	19
GO:00488133	Liver	NAFLD	dendrite morphogenesis	29/1882	146/18723	2.63e-04	4.26e-03	29
GO:00109755	Liver	NAFLD	regulation of neuron projection development	64/1882	445/18723	2.12e-03	2.08e-02	64
GO:004819311	Liver	Cirrhotic	Golgi vesicle transport	153/4634	296/18723	1.02e-23	6.43e-21	153
GO:002260412	Liver	Cirrhotic	regulation of cell morphogenesis	127/4634	309/18723	1.45e-10	7.44e-09	127
GO:001076912	Liver	Cirrhotic	regulation of cell morphogenesis involved in differentiation	43/4634	96/18723	1.42e-05	1.97e-04	43
GO:001077012	Liver	Cirrhotic	positive regulation of cell morphogenesis involved in differentiation	35/4634	79/18723	1.13e-04	1.14e-03	35
GO:00107205	Liver	Cirrhotic	positive regulation of cell development	99/4634	298/18723	5.71e-04	4.46e-03	99

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
CUX1	ASC	Colorectum	FAP	XACT,RNF43,BACE2, etc.	2.91e-01
CUX1	pDC	Liver	Cirrhotic	RASA3,ZDHHC12,TMEM220, etc.	2.15e-01
CUX1	LC	Lung	Healthy	PSMB4,GLOD4,FCGR2B, etc.	1.48e-03

∗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

CUX1

SNV

Missense_Mutation

c.2893N>A

p.Glu965Lys

p.E965K

P39880

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-A2-A0D2-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

CUX1

SNV

Missense_Mutation

rs782031337

c.2470N>C

p.Glu824Gln

p.E824Q

P39880

protein_coding

deleterious(0)

possibly_damaging(0.57)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CUX1

SNV

Missense_Mutation

novel

c.213N>A

p.Phe71Leu

p.F71L

P39880

protein_coding

deleterious(0.04)

probably_damaging(0.969)

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

CUX1

SNV

Missense_Mutation

rs782680467

c.352N>T

p.Arg118Cys

p.R118C

P39880

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-B6-A0IB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

CUX1

SNV

Missense_Mutation

c.1879G>A

p.Asp627Asn

p.D627N

P39880

protein_coding

deleterious(0.02)

probably_damaging(0.992)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

CUX1

SNV

Missense_Mutation

rs369468371

c.2575N>A

p.Gly859Ser

p.G859S

P39880

protein_coding

tolerated(1)

benign(0)

TCGA-D8-A1XZ-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

tamoxiphen+anastrozolum

CUX1

SNV

Missense_Mutation

c.1976N>A

p.Arg659Gln

p.R659Q

P39880

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(0.99)

TCGA-D8-A27G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CUX1

SNV

Missense_Mutation

novel

c.1079N>T

p.Ala360Val

p.A360V

P39880

protein_coding

tolerated(0.21)

possibly_damaging(0.647)

TCGA-E9-A54Y-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

CUX1

SNV

Missense_Mutation

rs369826605

c.2896N>C

p.Lys966Gln

p.K966Q

P39880

protein_coding

deleterious(0.02)

probably_damaging(0.997)

TCGA-LL-A441-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

CUX1

insertion

In_Frame_Ins

novel

c.167_168insGACCCA

p.Thr56_Pro57insThrHis

p.T56_P57insTH

P39880

protein_coding

TCGA-A8-A06Q-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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