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: NMB

Gene summary for NMB

Gene summary.

Gene information	Species	Human
	Gene symbol	NMB
	Gene ID	4828
	Gene name	neuromedin B
	Gene Alias	NMB
	Cytomap	15q25.2
	Gene Type	protein-coding
	GO ID	GO:0006810
	UniProtAcc	P08949

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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
4828	NMB	LZE4T	Human	Esophagus	ESCC	4.10e-49	2.19e+00	0.0811
4828	NMB	LZE7T	Human	Esophagus	ESCC	6.86e-07	6.66e-01	0.0667
4828	NMB	LZE20T	Human	Esophagus	ESCC	3.35e-09	4.98e-01	0.0662
4828	NMB	LZE22T	Human	Esophagus	ESCC	7.33e-10	8.66e-01	0.068
4828	NMB	LZE24T	Human	Esophagus	ESCC	2.62e-07	3.64e-01	0.0596
4828	NMB	P1T-E	Human	Esophagus	ESCC	7.84e-10	6.11e-01	0.0875
4828	NMB	P2T-E	Human	Esophagus	ESCC	1.68e-14	2.94e-01	0.1177
4828	NMB	P4T-E	Human	Esophagus	ESCC	5.38e-63	1.97e+00	0.1323
4828	NMB	P5T-E	Human	Esophagus	ESCC	2.54e-23	6.82e-01	0.1327
4828	NMB	P8T-E	Human	Esophagus	ESCC	2.92e-27	5.41e-01	0.0889
4828	NMB	P9T-E	Human	Esophagus	ESCC	5.15e-61	1.65e+00	0.1131
4828	NMB	P10T-E	Human	Esophagus	ESCC	6.29e-13	3.09e-01	0.116
4828	NMB	P11T-E	Human	Esophagus	ESCC	1.08e-12	9.97e-01	0.1426
4828	NMB	P12T-E	Human	Esophagus	ESCC	1.54e-13	3.44e-01	0.1122
4828	NMB	P15T-E	Human	Esophagus	ESCC	1.58e-38	1.18e+00	0.1149
4828	NMB	P16T-E	Human	Esophagus	ESCC	1.06e-29	5.77e-01	0.1153
4828	NMB	P17T-E	Human	Esophagus	ESCC	1.13e-05	2.24e-01	0.1278
4828	NMB	P19T-E	Human	Esophagus	ESCC	6.56e-09	1.86e+00	0.1662
4828	NMB	P20T-E	Human	Esophagus	ESCC	6.95e-13	4.38e-01	0.1124
4828	NMB	P21T-E	Human	Esophagus	ESCC	5.48e-62	1.79e+00	0.1617

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:003294311	Cervix	HSIL_HPV	mononuclear cell proliferation	25/737	291/18723	2.27e-04	4.03e-03	25
GO:190134211	Cervix	HSIL_HPV	regulation of vasculature development	28/737	348/18723	2.92e-04	4.81e-03	28
GO:004576511	Cervix	HSIL_HPV	regulation of angiogenesis	27/737	342/18723	5.00e-04	7.22e-03	27
GO:00326407	Cervix	HSIL_HPV	tumor necrosis factor production	17/737	181/18723	8.23e-04	1.07e-02	17
GO:00326807	Cervix	HSIL_HPV	regulation of tumor necrosis factor production	17/737	181/18723	8.23e-04	1.07e-02	17
GO:00717067	Cervix	HSIL_HPV	tumor necrosis factor superfamily cytokine production	17/737	186/18723	1.11e-03	1.36e-02	17
GO:19035557	Cervix	HSIL_HPV	regulation of tumor necrosis factor superfamily cytokine production	17/737	186/18723	1.11e-03	1.36e-02	17
GO:00026951	Cervix	HSIL_HPV	negative regulation of leukocyte activation	17/737	187/18723	1.18e-03	1.41e-02	17
GO:00512501	Cervix	HSIL_HPV	negative regulation of lymphocyte activation	15/737	157/18723	1.37e-03	1.56e-02	15
GO:007037112	Cervix	HSIL_HPV	ERK1 and ERK2 cascade	25/737	330/18723	1.42e-03	1.59e-02	25
GO:00508661	Cervix	HSIL_HPV	negative regulation of cell activation	18/737	210/18723	1.68e-03	1.81e-02	18
GO:190121415	Cervix	HSIL_HPV	regulation of neuron death	24/737	319/18723	1.92e-03	2.02e-02	24
GO:002240811	Cervix	HSIL_HPV	negative regulation of cell-cell adhesion	17/737	196/18723	1.97e-03	2.06e-02	17
GO:007037211	Cervix	HSIL_HPV	regulation of ERK1 and ERK2 cascade	23/737	309/18723	2.70e-03	2.58e-02	23
GO:0001818	Cervix	HSIL_HPV	negative regulation of cytokine production	25/737	357/18723	4.05e-03	3.47e-02	25
GO:000734610	Esophagus	HGIN	regulation of mitotic cell cycle	98/2587	457/18723	4.39e-06	1.42e-04	98
GO:007099727	Esophagus	HGIN	neuron death	81/2587	361/18723	5.01e-06	1.61e-04	81
GO:00447729	Esophagus	HGIN	mitotic cell cycle phase transition	89/2587	424/18723	2.80e-05	7.21e-04	89
GO:19019906	Esophagus	HGIN	regulation of mitotic cell cycle phase transition	65/2587	299/18723	1.12e-04	2.36e-03	65
GO:190121424	Esophagus	HGIN	regulation of neuron death	68/2587	319/18723	1.46e-04	2.91e-03	68

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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

NMB

insertion

Frame_Shift_Ins

novel

c.230_231insAGCATATAGTGTGTGCATTTTGAAGGGA

p.Arg78AlafsTer19

p.R78Afs*19

P08949

protein_coding

TCGA-A2-A0CP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

NMB

SNV

Missense_Mutation

c.365C>A

p.Pro122Gln

p.P122Q

P08949

protein_coding

tolerated_low_confidence(0.25)

benign(0.005)

TCGA-G4-6309-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Chemotherapy

xeloda

NMB

SNV

Missense_Mutation

novel

c.384N>C

p.Gln128His

p.Q128H

P08949

protein_coding

tolerated_low_confidence(0.21)

benign(0.138)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

NMB

SNV

Missense_Mutation

novel

c.418G>T

p.Val140Leu

p.V140L

P08949

protein_coding

tolerated_low_confidence(0.59)

benign(0.001)

TCGA-AJ-A3BG-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Chemotherapy

carboplatin

NMB

SNV

Missense_Mutation

c.341N>A

p.Gly114Asp

p.G114D

P08949

protein_coding

tolerated_low_confidence(0.12)

benign(0.058)

TCGA-BS-A0U7-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

NMB

SNV

Missense_Mutation

c.406N>A

p.His136Asn

p.H136N

P08949

protein_coding

tolerated_low_confidence(0.05)

benign(0.015)

TCGA-D1-A0ZS-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

NMB

SNV

Missense_Mutation

c.388C>T

p.Arg130Cys

p.R130C

P08949

protein_coding

tolerated_low_confidence(0.05)

benign(0.003)

TCGA-D1-A103-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

NMB

SNV

Missense_Mutation

novel

c.455G>A

p.Cys152Tyr

p.C152Y

P08949

protein_coding

deleterious_low_confidence(0.02)

benign(0.01)

TCGA-22-1002-01

Lung

lung squamous cell carcinoma

Male

>=65

I/II

Unknown

NMB

SNV

Missense_Mutation

novel

c.83G>A

p.Ser28Asn

p.S28N

P08949

protein_coding

tolerated(0.13)

benign(0.006)

TCGA-CN-5373-01

Oral cavity

head & neck squamous cell carcinoma

Female

<65

I/II

Unknown

NMB

SNV

Missense_Mutation

novel

c.289G>C

p.Ala97Pro

p.A97P

P08949

protein_coding

deleterious(0.02)

possibly_damaging(0.735)

TCGA-CR-7364-01

Oral cavity

head & neck squamous cell carcinoma

Male

>=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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