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: PELI1

Gene summary for PELI1

Gene summary.

Gene information	Species	Human
	Gene symbol	PELI1
	Gene ID	57162
	Gene name	pellino E3 ubiquitin protein ligase 1
	Gene Alias	PELI1
	Cytomap	2p14
	Gene Type	protein-coding
	GO ID	GO:0000209
	UniProtAcc	Q53T26

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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
57162	PELI1	CCI_1	Human	Cervix	CC	3.13e-09	1.44e+00	0.528
57162	PELI1	CCI_3	Human	Cervix	CC	1.90e-04	6.26e-01	0.516
57162	PELI1	HTA11_3410_2000001011	Human	Colorectum	AD	3.23e-04	-2.96e-01	0.0155
57162	PELI1	HTA11_3361_2000001011	Human	Colorectum	AD	9.65e-06	-5.58e-01	-0.1207
57162	PELI1	HTA11_866_3004761011	Human	Colorectum	AD	3.92e-04	-3.60e-01	0.096
57162	PELI1	HTA11_7696_3000711011	Human	Colorectum	AD	2.19e-02	-3.68e-01	0.0674
57162	PELI1	HTA11_99999971662_82457	Human	Colorectum	MSS	1.12e-03	-3.53e-01	0.3859
57162	PELI1	HTA11_99999973899_84307	Human	Colorectum	MSS	3.61e-03	-5.20e-01	0.2585
57162	PELI1	HTA11_99999974143_84620	Human	Colorectum	MSS	6.66e-04	-3.31e-01	0.3005
57162	PELI1	A015-C-203	Human	Colorectum	FAP	1.22e-19	-3.19e-01	-0.1294
57162	PELI1	A015-C-204	Human	Colorectum	FAP	1.19e-03	-2.66e-01	-0.0228
57162	PELI1	A014-C-040	Human	Colorectum	FAP	4.99e-04	-4.51e-01	-0.1184
57162	PELI1	A002-C-201	Human	Colorectum	FAP	7.12e-13	-3.70e-01	0.0324
57162	PELI1	A001-C-119	Human	Colorectum	FAP	4.08e-08	-3.86e-01	-0.1557
57162	PELI1	A001-C-108	Human	Colorectum	FAP	1.87e-13	-3.70e-01	-0.0272
57162	PELI1	A002-C-205	Human	Colorectum	FAP	8.06e-25	-5.67e-01	-0.1236
57162	PELI1	A015-C-005	Human	Colorectum	FAP	4.36e-02	-1.49e-01	-0.0336
57162	PELI1	A015-C-006	Human	Colorectum	FAP	1.17e-16	-5.66e-01	-0.0994
57162	PELI1	A015-C-106	Human	Colorectum	FAP	1.79e-05	-2.86e-01	-0.0511
57162	PELI1	A002-C-114	Human	Colorectum	FAP	6.59e-18	-5.04e-01	-0.1561

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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
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
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:00709366	Cervix	CC	protein K48-linked ubiquitination	22/2311	65/18723	5.56e-06	1.38e-04	22
GO:00706637	Cervix	CC	regulation of leukocyte proliferation	55/2311	245/18723	6.51e-06	1.56e-04	55
GO:00506705	Cervix	CC	regulation of lymphocyte proliferation	51/2311	225/18723	1.05e-05	2.32e-04	51
GO:0051250	Cervix	CC	negative regulation of lymphocyte activation	39/2311	157/18723	1.23e-05	2.57e-04	39
GO:00329444	Cervix	CC	regulation of mononuclear cell proliferation	51/2311	227/18723	1.36e-05	2.73e-04	51
GO:00706617	Cervix	CC	leukocyte proliferation	65/2311	318/18723	2.56e-05	4.32e-04	65
GO:0002695	Cervix	CC	negative regulation of leukocyte activation	43/2311	187/18723	3.47e-05	5.60e-04	43
GO:00431228	Cervix	CC	regulation of I-kappaB kinase/NF-kappaB signaling	53/2311	249/18723	4.50e-05	6.87e-04	53
GO:00466516	Cervix	CC	lymphocyte proliferation	59/2311	288/18723	5.53e-05	8.10e-04	59
GO:0050868	Cervix	CC	negative regulation of T cell activation	31/2311	122/18723	5.81e-05	8.46e-04	31
GO:00329435	Cervix	CC	mononuclear cell proliferation	59/2311	291/18723	7.51e-05	1.03e-03	59
GO:00022212	Cervix	CC	pattern recognition receptor signaling pathway	39/2311	172/18723	1.08e-04	1.38e-03	39
GO:00622073	Cervix	CC	regulation of pattern recognition receptor signaling pathway	27/2311	105/18723	1.37e-04	1.68e-03	27
GO:00072497	Cervix	CC	I-kappaB kinase/NF-kappaB signaling	56/2311	281/18723	1.81e-04	2.12e-03	56
GO:1903038	Cervix	CC	negative regulation of leukocyte cell-cell adhesion	33/2311	141/18723	1.90e-04	2.21e-03	33
GO:0050866	Cervix	CC	negative regulation of cell activation	44/2311	210/18723	2.76e-04	3.02e-03	44
GO:00026967	Cervix	CC	positive regulation of leukocyte activation	72/2311	409/18723	1.13e-03	9.31e-03	72
GO:00512516	Cervix	CC	positive regulation of lymphocyte activation	65/2311	362/18723	1.15e-03	9.39e-03	65
GO:00508676	Cervix	CC	positive regulation of cell activation	73/2311	420/18723	1.50e-03	1.16e-02	73
GO:00431237	Cervix	CC	positive regulation of I-kappaB kinase/NF-kappaB signaling	37/2311	186/18723	2.15e-03	1.55e-02	37

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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

PELI1

SNV

Missense_Mutation

c.1156N>T

p.His386Tyr

p.H386Y

Q96FA3

protein_coding

deleterious(0.02)

probably_damaging(0.998)

TCGA-A2-A0EY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

PELI1

SNV

Missense_Mutation

rs761769713

c.977G>A

p.Arg326His

p.R326H

Q96FA3

protein_coding

deleterious(0.04)

possibly_damaging(0.506)

TCGA-AO-A0J4-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

PELI1

insertion

Frame_Shift_Ins

novel

c.346_347insCCTACGTGAAACCAGATCGGCTCAGCAGAGAGGA

p.Asp116AlafsTer20

p.D116Afs*20

Q96FA3

protein_coding

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

PELI1

insertion

Frame_Shift_Ins

novel

c.340_341insC

p.Val114AlafsTer3

p.V114Afs*3

Q96FA3

protein_coding

TCGA-B6-A0IB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

PELI1

insertion

Frame_Shift_Ins

novel

c.339_340insCTCATACTTTTCATGCAGCCTGTCCCTTTTGTGCACATCAGTTG

p.Val114LeufsTer16

p.V114Lfs*16

Q96FA3

protein_coding

TCGA-B6-A0IB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

PELI1

SNV

Missense_Mutation

c.1181C>T

p.Ala394Val

p.A394V

Q96FA3

protein_coding

tolerated(0.84)

benign(0.284)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

PELI1

SNV

Missense_Mutation

c.1174N>T

p.His392Tyr

p.H392Y

Q96FA3

protein_coding

deleterious(0.01)

possibly_damaging(0.876)

TCGA-DS-A1OC-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

gemcitabine

PELI1

SNV

Missense_Mutation

rs761769713

c.977N>A

p.Arg326His

p.R326H

Q96FA3

protein_coding

deleterious(0.04)

possibly_damaging(0.506)

TCGA-MA-AA42-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

PELI1

SNV

Missense_Mutation

c.895N>A

p.Val299Ile

p.V299I

Q96FA3

protein_coding

tolerated(0.31)

benign(0.007)

TCGA-A6-6654-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Chemotherapy

oxaliplatin

PELI1

SNV

Missense_Mutation

rs768293813

c.859A>G

p.Asn287Asp

p.N287D

Q96FA3

protein_coding

deleterious(0)

possibly_damaging(0.627)

TCGA-AA-3833-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

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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