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: GLCE

Gene summary for GLCE

Gene summary.

Gene information	Species	Human
	Gene symbol	GLCE
	Gene ID	26035
	Gene name	glucuronic acid epimerase
	Gene Alias	HSEPI
	Cytomap	15q23
	Gene Type	protein-coding
	GO ID	GO:0006022
	UniProtAcc	O94923

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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
26035	GLCE	P40T-E	Human	Esophagus	ESCC	4.28e-06	2.34e-01	0.109
26035	GLCE	P42T-E	Human	Esophagus	ESCC	7.67e-03	1.60e-01	0.1175
26035	GLCE	P44T-E	Human	Esophagus	ESCC	3.79e-06	1.24e-01	0.1096
26035	GLCE	P47T-E	Human	Esophagus	ESCC	5.55e-06	7.82e-02	0.1067
26035	GLCE	P48T-E	Human	Esophagus	ESCC	1.18e-07	1.94e-01	0.0959
26035	GLCE	P49T-E	Human	Esophagus	ESCC	3.00e-05	6.23e-01	0.1768
26035	GLCE	P52T-E	Human	Esophagus	ESCC	7.38e-14	3.42e-01	0.1555
26035	GLCE	P54T-E	Human	Esophagus	ESCC	6.49e-15	2.19e-01	0.0975
26035	GLCE	P56T-E	Human	Esophagus	ESCC	5.81e-05	3.80e-01	0.1613
26035	GLCE	P57T-E	Human	Esophagus	ESCC	1.15e-14	2.37e-01	0.0926
26035	GLCE	P61T-E	Human	Esophagus	ESCC	5.33e-12	2.12e-01	0.099
26035	GLCE	P62T-E	Human	Esophagus	ESCC	2.85e-12	1.03e-01	0.1302
26035	GLCE	P65T-E	Human	Esophagus	ESCC	3.47e-09	1.62e-01	0.0978
26035	GLCE	P74T-E	Human	Esophagus	ESCC	2.36e-03	1.92e-01	0.1479
26035	GLCE	P75T-E	Human	Esophagus	ESCC	2.36e-16	2.92e-01	0.1125
26035	GLCE	P76T-E	Human	Esophagus	ESCC	2.04e-12	2.63e-01	0.1207
26035	GLCE	P79T-E	Human	Esophagus	ESCC	4.71e-12	1.10e-01	0.1154
26035	GLCE	P80T-E	Human	Esophagus	ESCC	3.30e-02	6.76e-02	0.155
26035	GLCE	P82T-E	Human	Esophagus	ESCC	8.83e-12	3.95e-01	0.1072
26035	GLCE	P83T-E	Human	Esophagus	ESCC	1.13e-21	6.34e-01	0.1738

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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

∗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:0006790	Colorectum	AD	sulfur compound metabolic process	101/3918	339/18723	6.46e-05	1.07e-03	101
GO:00067901	Colorectum	SER	sulfur compound metabolic process	73/2897	339/18723	1.75e-03	1.81e-02	73
GO:00067902	Colorectum	MSS	sulfur compound metabolic process	85/3467	339/18723	1.52e-03	1.39e-02	85
GO:0009101	Colorectum	FAP	glycoprotein biosynthetic process	63/2622	317/18723	2.31e-03	1.86e-02	63
GO:00091002	Esophagus	ESCC	glycoprotein metabolic process	226/8552	387/18723	2.64e-07	3.94e-06	226
GO:00067906	Esophagus	ESCC	sulfur compound metabolic process	201/8552	339/18723	2.64e-07	3.94e-06	201
GO:00442725	Esophagus	ESCC	sulfur compound biosynthetic process	96/8552	148/18723	1.86e-06	2.16e-05	96
GO:00091012	Esophagus	ESCC	glycoprotein biosynthetic process	181/8552	317/18723	2.54e-05	2.15e-04	181
GO:0006029	Esophagus	ESCC	proteoglycan metabolic process	48/8552	79/18723	4.93e-03	1.89e-02	48
GO:0030166	Esophagus	ESCC	proteoglycan biosynthetic process	35/8552	56/18723	8.30e-03	2.94e-02	35
GO:0006024	Esophagus	ESCC	glycosaminoglycan biosynthetic process	45/8552	75/18723	8.75e-03	3.08e-02	45
GO:0006023	Esophagus	ESCC	aminoglycan biosynthetic process	47/8552	79/18723	9.29e-03	3.23e-02	47
GO:0030201	Esophagus	ESCC	heparan sulfate proteoglycan metabolic process	21/8552	31/18723	1.10e-02	3.70e-02	21
GO:00067904	Liver	NAFLD	sulfur compound metabolic process	58/1882	339/18723	3.79e-05	9.38e-04	58
GO:0044272	Liver	NAFLD	sulfur compound biosynthetic process	28/1882	148/18723	7.52e-04	9.52e-03	28
GO:000679021	Liver	HCC	sulfur compound metabolic process	212/7958	339/18723	5.60e-14	3.39e-12	212
GO:00442722	Liver	HCC	sulfur compound biosynthetic process	95/7958	148/18723	7.89e-08	1.58e-06	95
GO:0009100	Liver	HCC	glycoprotein metabolic process	193/7958	387/18723	1.89e-03	9.62e-03	193
GO:00442724	Oral cavity	OSCC	sulfur compound biosynthetic process	82/7305	148/18723	3.71e-05	3.31e-04	82
GO:00067905	Oral cavity	OSCC	sulfur compound metabolic process	168/7305	339/18723	4.50e-05	3.84e-04	168

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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

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

GLCE

SNV

Missense_Mutation

c.1423G>A

p.Ala475Thr

p.A475T

O94923

protein_coding

tolerated(0.5)

benign(0.265)

TCGA-A8-A09M-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

paclitaxel

GLCE

SNV

Missense_Mutation

c.1166N>C

p.Gly389Ala

p.G389A

O94923

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-B6-A1KF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

GLCE

SNV

Missense_Mutation

rs184777253

c.202N>A

p.Val68Met

p.V68M

O94923

protein_coding

tolerated_low_confidence(0.16)

benign(0)

TCGA-BH-A0H6-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

GLCE

SNV

Missense_Mutation

c.235N>G

p.Gln79Glu

p.Q79E

O94923

protein_coding

tolerated_low_confidence(0.45)

benign(0.006)

TCGA-BH-A18P-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

GLCE

SNV

Missense_Mutation

c.587N>T

p.Gly196Val

p.G196V

O94923

protein_coding

deleterious(0)

probably_damaging(0.982)

TCGA-BH-A1FR-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

GLCE

SNV

Missense_Mutation

novel

c.1406C>T

p.Ser469Leu

p.S469L

O94923

protein_coding

deleterious(0)

benign(0.138)

TCGA-PE-A5DE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

GLCE

insertion

In_Frame_Ins

novel

c.991_992insGTACAAATGTTAAAAAGCTTATCTGTAGCCTAC

p.Ala331delinsGlyThrAsnValLysLysLeuIleCysSerLeuPro

p.A331delinsGTNVKKLICSLP

O94923

protein_coding

TCGA-AN-A0FN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

GLCE

insertion

Nonsense_Mutation

novel

c.227_228insGATCCAAAATTGTCCTAATACAGTTGTTCAACATTAAAA

p.Ala76_Phe77insIleGlnAsnCysProAsnThrValValGlnHisTerLys

p.A76_F77insIQNCPNTVVQH*K

O94923

protein_coding

TCGA-BH-A0BR-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

GLCE

SNV

Missense_Mutation

c.1228N>A

p.Asp410Asn

p.D410N

O94923

protein_coding

tolerated(0.66)

benign(0)

TCGA-DS-A1OC-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

gemcitabine

GLCE

SNV

Missense_Mutation

c.178N>A

p.Glu60Lys

p.E60K

O94923

protein_coding

tolerated_low_confidence(0.25)

benign(0.018)

TCGA-VS-A8QM-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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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