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:19012156	Liver	Cirrhotic	negative regulation of neuron death	80/4634	208/18723	7.55e-06	1.15e-04	80
GO:00073463	Liver	Cirrhotic	regulation of mitotic cell cycle	154/4634	457/18723	8.73e-06	1.29e-04	154
GO:00447721	Liver	Cirrhotic	mitotic cell cycle phase transition	139/4634	424/18723	1.02e-04	1.06e-03	139
GO:00016495	Liver	Cirrhotic	osteoblast differentiation	80/4634	229/18723	3.39e-04	2.91e-03	80
GO:1901990	Liver	Cirrhotic	regulation of mitotic cell cycle phase transition	100/4634	299/18723	4.13e-04	3.41e-03	100
GO:00015035	Liver	Cirrhotic	ossification	127/4634	408/18723	1.89e-03	1.19e-02	127
GO:2000045	Liver	Cirrhotic	regulation of G1/S transition of mitotic cell cycle	51/4634	142/18723	1.91e-03	1.20e-02	51
GO:00000821	Liver	Cirrhotic	G1/S transition of mitotic cell cycle	72/4634	214/18723	2.07e-03	1.28e-02	72
GO:00487711	Liver	Cirrhotic	tissue remodeling	60/4634	175/18723	2.86e-03	1.65e-02	60
GO:00448431	Liver	Cirrhotic	cell cycle G1/S phase transition	77/4634	241/18723	6.68e-03	3.30e-02	77
GO:00071624	Liver	Cirrhotic	negative regulation of cell adhesion	93/4634	303/18723	1.06e-02	4.66e-02	93
GO:00447722	Liver	HCC	mitotic cell cycle phase transition	240/7958	424/18723	2.47e-09	6.84e-08	240
GO:000734611	Liver	HCC	regulation of mitotic cell cycle	255/7958	457/18723	4.96e-09	1.30e-07	255
GO:001003822	Liver	HCC	response to metal ion	208/7958	373/18723	1.35e-07	2.56e-06	208
GO:007099722	Liver	HCC	neuron death	202/7958	361/18723	1.44e-07	2.70e-06	202
GO:190121412	Liver	HCC	regulation of neuron death	179/7958	319/18723	5.65e-07	9.01e-06	179
GO:19019901	Liver	HCC	regulation of mitotic cell cycle phase transition	167/7958	299/18723	1.96e-06	2.71e-05	167
GO:19019871	Liver	HCC	regulation of cell cycle phase transition	211/7958	390/18723	2.11e-06	2.89e-05	211
GO:0045786	Liver	HCC	negative regulation of cell cycle	204/7958	385/18723	1.84e-05	1.99e-04	204
GO:00448432	Liver	HCC	cell cycle G1/S phase transition	134/7958	241/18723	2.60e-05	2.70e-04	134

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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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