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	LN46	Human	Oral cavity	OSCC	1.35e-12	6.78e-01	0.1666
4828	NMB	LP15	Human	Oral cavity	LP	8.33e-11	1.79e+00	0.2174
4828	NMB	LP17	Human	Oral cavity	LP	6.69e-10	1.31e+00	0.2349
4828	NMB	SYSMH1	Human	Oral cavity	OSCC	1.89e-71	1.47e+00	0.1127
4828	NMB	SYSMH2	Human	Oral cavity	OSCC	3.67e-20	9.27e-01	0.2326
4828	NMB	SYSMH3	Human	Oral cavity	OSCC	1.08e-16	4.93e-01	0.2442
4828	NMB	SYSMH5	Human	Oral cavity	OSCC	8.69e-06	1.32e-01	0.0647
4828	NMB	P10_cSCC	Human	Skin	cSCC	6.23e-10	6.84e-01	0.1017
4828	NMB	male-WTA	Human	Thyroid	PTC	2.99e-25	2.99e-01	0.1037
4828	NMB	PTC01	Human	Thyroid	PTC	1.22e-15	5.81e-01	0.1899
4828	NMB	PTC04	Human	Thyroid	PTC	8.01e-20	1.17e+00	0.1927
4828	NMB	PTC05	Human	Thyroid	PTC	3.79e-28	2.03e+00	0.2065
4828	NMB	PTC06	Human	Thyroid	PTC	1.81e-48	2.10e+00	0.2057
4828	NMB	PTC07	Human	Thyroid	PTC	2.29e-80	2.00e+00	0.2044
4828	NMB	ATC11	Human	Thyroid	ATC	2.02e-03	8.84e-02	0.3386
4828	NMB	ATC12	Human	Thyroid	ATC	8.13e-05	2.83e-01	0.34
4828	NMB	ATC3	Human	Thyroid	ATC	3.01e-02	1.76e-02	0.338
4828	NMB	ATC4	Human	Thyroid	ATC	1.72e-10	4.34e-01	0.34

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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:007099714	Breast	IDC	neuron death	57/1434	361/18723	1.31e-07	7.38e-06	57
GO:190121414	Breast	IDC	regulation of neuron death	48/1434	319/18723	5.01e-06	1.69e-04	48
GO:004211012	Breast	IDC	T cell activation	64/1434	487/18723	1.49e-05	3.77e-04	64
GO:005086311	Breast	IDC	regulation of T cell activation	47/1434	329/18723	2.49e-05	5.91e-04	47
GO:000164912	Breast	IDC	osteoblast differentiation	35/1434	229/18723	6.64e-05	1.35e-03	35
GO:000715912	Breast	IDC	leukocyte cell-cell adhesion	49/1434	371/18723	1.27e-04	2.33e-03	49
GO:000268311	Breast	IDC	negative regulation of immune system process	55/1434	434/18723	1.53e-04	2.67e-03	55
GO:190303711	Breast	IDC	regulation of leukocyte cell-cell adhesion	45/1434	336/18723	1.72e-04	2.92e-03	45
GO:00457651	Breast	IDC	regulation of angiogenesis	45/1434	342/18723	2.57e-04	3.98e-03	45
GO:002240712	Breast	IDC	regulation of cell-cell adhesion	55/1434	448/18723	3.43e-04	5.07e-03	55
GO:19013421	Breast	IDC	regulation of vasculature development	45/1434	348/18723	3.78e-04	5.38e-03	45
GO:00703713	Breast	IDC	ERK1 and ERK2 cascade	43/1434	330/18723	4.28e-04	5.84e-03	43
GO:000150311	Breast	IDC	ossification	50/1434	408/18723	6.51e-04	8.04e-03	50
GO:190121513	Breast	IDC	negative regulation of neuron death	29/1434	208/18723	1.23e-03	1.32e-02	29
GO:004209812	Breast	IDC	T cell proliferation	28/1434	199/18723	1.29e-03	1.35e-02	28
GO:004212911	Breast	IDC	regulation of T cell proliferation	25/1434	171/18723	1.32e-03	1.38e-02	25
GO:003264011	Breast	IDC	tumor necrosis factor production	25/1434	181/18723	2.92e-03	2.53e-02	25
GO:003268011	Breast	IDC	regulation of tumor necrosis factor production	25/1434	181/18723	2.92e-03	2.53e-02	25
GO:00071625	Breast	IDC	negative regulation of cell adhesion	37/1434	303/18723	3.27e-03	2.75e-02	37
GO:007170611	Breast	IDC	tumor necrosis factor superfamily cytokine production	25/1434	186/18723	4.21e-03	3.31e-02	25

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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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