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:002260410	Cervix	CC	regulation of cell morphogenesis	84/2311	309/18723	1.00e-12	4.29e-10	84
GO:00107699	Cervix	CC	regulation of cell morphogenesis involved in differentiation	31/2311	96/18723	2.43e-07	1.05e-05	31
GO:00163587	Cervix	CC	dendrite development	58/2311	243/18723	4.52e-07	1.76e-05	58
GO:00109757	Cervix	CC	regulation of neuron projection development	88/2311	445/18723	4.26e-06	1.09e-04	88
GO:00107206	Cervix	CC	positive regulation of cell development	64/2311	298/18723	5.69e-06	1.41e-04	64
GO:00313467	Cervix	CC	positive regulation of cell projection organization	72/2311	353/18723	1.04e-05	2.32e-04	72
GO:00107708	Cervix	CC	positive regulation of cell morphogenesis involved in differentiation	23/2311	79/18723	5.44e-05	8.04e-04	23
GO:00481938	Cervix	CC	Golgi vesicle transport	58/2311	296/18723	2.24e-04	2.54e-03	58
GO:00519603	Cervix	CC	regulation of nervous system development	77/2311	443/18723	1.13e-03	9.30e-03	77
GO:00507676	Cervix	CC	regulation of neurogenesis	65/2311	364/18723	1.33e-03	1.05e-02	65
GO:00507694	Cervix	CC	positive regulation of neurogenesis	43/2311	225/18723	2.25e-03	1.61e-02	43
GO:00488135	Cervix	CC	dendrite morphogenesis	30/2311	146/18723	3.27e-03	2.13e-02	30
GO:00519622	Cervix	CC	positive regulation of nervous system development	48/2311	272/18723	6.60e-03	3.65e-02	48
GO:00507733	Cervix	CC	regulation of dendrite development	22/2311	103/18723	6.75e-03	3.71e-02	22
GO:0048193	Colorectum	AD	Golgi vesicle transport	109/3918	296/18723	1.80e-10	1.68e-08	109
GO:0022604	Colorectum	AD	regulation of cell morphogenesis	109/3918	309/18723	3.08e-09	2.07e-07	109
GO:0010975	Colorectum	AD	regulation of neuron projection development	129/3918	445/18723	2.88e-05	5.37e-04	129
GO:0031346	Colorectum	AD	positive regulation of cell projection organization	104/3918	353/18723	8.26e-05	1.30e-03	104
GO:0010769	Colorectum	AD	regulation of cell morphogenesis involved in differentiation	35/3918	96/18723	3.26e-04	3.85e-03	35
GO:0010770	Colorectum	AD	positive regulation of cell morphogenesis involved in differentiation	30/3918	79/18723	3.81e-04	4.38e-03	30

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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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