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: SCEL

Gene summary for SCEL

Gene summary.

Gene information	Species	Human
	Gene symbol	SCEL
	Gene ID	8796
	Gene name	sciellin
	Gene Alias	SCEL
	Cytomap	13q22.3
	Gene Type	protein-coding
	GO ID	GO:0007154
	UniProtAcc	O95171

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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
8796	SCEL	CCI_1	Human	Cervix	CC	6.54e-03	5.56e-01	0.528
8796	SCEL	H2	Human	Cervix	HSIL_HPV	1.13e-18	6.77e-01	0.0632
8796	SCEL	P39T-E	Human	Esophagus	ESCC	1.13e-16	6.04e-01	0.0894
8796	SCEL	P74T-E	Human	Esophagus	ESCC	1.86e-07	4.98e-01	0.1479
8796	SCEL	P82T-E	Human	Esophagus	ESCC	1.40e-05	6.05e-01	0.1072
8796	SCEL	P84T-E	Human	Esophagus	ESCC	8.33e-03	1.13e+00	0.0933
8796	SCEL	C21	Human	Oral cavity	OSCC	3.80e-05	6.42e-01	0.2678
8796	SCEL	C57	Human	Oral cavity	OSCC	1.94e-29	1.03e+00	0.1679
8796	SCEL	C09	Human	Oral cavity	OSCC	9.02e-29	9.27e-01	0.1431
8796	SCEL	male-WTA	Human	Thyroid	PTC	1.47e-23	3.90e-01	0.1037
8796	SCEL	PTC01	Human	Thyroid	PTC	7.97e-04	2.29e-01	0.1899
8796	SCEL	PTC04	Human	Thyroid	PTC	1.23e-21	8.01e-01	0.1927
8796	SCEL	PTC05	Human	Thyroid	PTC	1.77e-18	8.54e-01	0.2065
8796	SCEL	PTC06	Human	Thyroid	PTC	9.62e-34	1.52e+00	0.2057
8796	SCEL	PTC07	Human	Thyroid	PTC	9.65e-28	8.45e-01	0.2044

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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
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
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:00085446	Cervix	CC	epidermis development	83/2311	324/18723	3.91e-11	8.54e-09	83
GO:00435884	Cervix	CC	skin development	71/2311	263/18723	8.04e-11	1.46e-08	71
GO:00160557	Cervix	CC	Wnt signaling pathway	98/2311	444/18723	4.82e-09	4.65e-07	98
GO:01987387	Cervix	CC	cell-cell signaling by wnt	98/2311	446/18723	6.16e-09	5.58e-07	98
GO:00302164	Cervix	CC	keratinocyte differentiation	42/2311	139/18723	1.74e-08	1.28e-06	42
GO:00301117	Cervix	CC	regulation of Wnt signaling pathway	76/2311	328/18723	3.05e-08	2.08e-06	76
GO:00099137	Cervix	CC	epidermal cell differentiation	53/2311	202/18723	5.48e-08	3.25e-06	53
GO:00608287	Cervix	CC	regulation of canonical Wnt signaling pathway	58/2311	253/18723	1.83e-06	5.89e-05	58
GO:00600707	Cervix	CC	canonical Wnt signaling pathway	66/2311	303/18723	2.47e-06	7.35e-05	66
GO:00096127	Cervix	CC	response to mechanical stimulus	48/2311	216/18723	3.23e-05	5.29e-04	48
GO:00301776	Cervix	CC	positive regulation of Wnt signaling pathway	31/2311	140/18723	8.01e-04	7.02e-03	31
GO:00902636	Cervix	CC	positive regulation of canonical Wnt signaling pathway	22/2311	106/18723	9.52e-03	4.72e-02	22
GO:000854413	Cervix	HSIL_HPV	epidermis development	38/737	324/18723	1.92e-09	3.23e-07	38
GO:003021611	Cervix	HSIL_HPV	keratinocyte differentiation	22/737	139/18723	2.53e-08	2.18e-06	22
GO:004358813	Cervix	HSIL_HPV	skin development	31/737	263/18723	5.32e-08	3.89e-06	31
GO:000991313	Cervix	HSIL_HPV	epidermal cell differentiation	26/737	202/18723	1.10e-07	7.15e-06	26
GO:000961212	Cervix	HSIL_HPV	response to mechanical stimulus	21/737	216/18723	1.31e-04	2.61e-03	21
GO:001605517	Esophagus	ESCC	Wnt signaling pathway	268/8552	444/18723	2.32e-10	6.58e-09	268
GO:019873817	Esophagus	ESCC	cell-cell signaling by wnt	269/8552	446/18723	2.41e-10	6.79e-09	269
GO:00435888	Esophagus	ESCC	skin development	163/8552	263/18723	6.48e-08	1.14e-06	163

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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

SCEL

SNV

Missense_Mutation

novel

c.1207N>T

p.Ser403Cys

p.S403C

O95171

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.591)

TCGA-A8-A07I-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

SCEL

SNV

Missense_Mutation

novel

c.1445N>A

p.Thr482Asn

p.T482N

O95171

protein_coding

tolerated(0.15)

benign(0.165)

TCGA-AC-A3QQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SCEL

SNV

Missense_Mutation

novel

c.277N>T

p.Asp93Tyr

p.D93Y

O95171

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SCEL

SNV

Missense_Mutation

rs201091090

c.991N>A

p.Glu331Lys

p.E331K

O95171

protein_coding

tolerated(0.27)

benign(0.009)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SCEL

SNV

Missense_Mutation

c.1547C>A

p.Pro516His

p.P516H

O95171

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SCEL

SNV

Missense_Mutation

c.1638N>A

p.Asn546Lys

p.N546K

O95171

protein_coding

deleterious(0.03)

benign(0.036)

TCGA-D8-A1XQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SCEL

insertion

Nonsense_Mutation

novel

c.2035_2036insCTTTTGGTAAATAGAAATATTTTCATTTATTACATTTTAGATC

p.Tyr679SerfsTer5

p.Y679Sfs*5

O95171

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SCEL

deletion

Frame_Shift_Del

novel

c.741delN

p.Ser248ValfsTer13

p.S248Vfs*13

O95171

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

SCEL

SNV

Missense_Mutation

novel

c.1166G>A

p.Ser389Asn

p.S389N

O95171

protein_coding

tolerated_low_confidence(0.07)

possibly_damaging(0.652)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SCEL

SNV

Missense_Mutation

novel

c.1476C>G

p.Ile492Met

p.I492M

O95171

protein_coding

deleterious(0)

probably_damaging(0.93)

TCGA-HM-A4S6-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

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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