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: NSMAF

Gene summary for NSMAF

Gene summary.

Gene information	Species	Human
	Gene symbol	NSMAF
	Gene ID	8439
	Gene name	neutral sphingomyelinase activation associated factor
	Gene Alias	FAN
	Cytomap	8q12.1
	Gene Type	protein-coding
	GO ID	GO:0006629
	UniProtAcc	Q92636

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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
8439	NSMAF	SYSMH1	Human	Oral cavity	OSCC	4.53e-06	1.51e-01	0.1127
8439	NSMAF	SYSMH2	Human	Oral cavity	OSCC	5.36e-07	2.13e-01	0.2326
8439	NSMAF	SYSMH3	Human	Oral cavity	OSCC	5.72e-13	3.04e-01	0.2442
8439	NSMAF	male-WTA	Human	Thyroid	PTC	5.35e-11	1.07e-01	0.1037
8439	NSMAF	PTC01	Human	Thyroid	PTC	1.56e-09	5.40e-02	0.1899
8439	NSMAF	PTC04	Human	Thyroid	PTC	4.41e-14	1.06e-01	0.1927
8439	NSMAF	PTC05	Human	Thyroid	PTC	3.43e-11	3.23e-01	0.2065
8439	NSMAF	PTC06	Human	Thyroid	PTC	7.20e-13	3.12e-01	0.2057
8439	NSMAF	PTC07	Human	Thyroid	PTC	5.12e-20	1.09e-01	0.2044
8439	NSMAF	ATC09	Human	Thyroid	ATC	3.28e-02	1.06e-01	0.2871
8439	NSMAF	ATC12	Human	Thyroid	ATC	8.18e-11	1.46e-01	0.34
8439	NSMAF	ATC13	Human	Thyroid	ATC	1.26e-25	3.95e-01	0.34
8439	NSMAF	ATC1	Human	Thyroid	ATC	4.75e-02	1.16e-01	0.2878
8439	NSMAF	ATC2	Human	Thyroid	ATC	2.80e-05	5.14e-01	0.34
8439	NSMAF	ATC4	Human	Thyroid	ATC	3.20e-09	2.21e-01	0.34
8439	NSMAF	ATC5	Human	Thyroid	ATC	3.70e-27	4.37e-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
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:00066433	Esophagus	ESCC	membrane lipid metabolic process	130/8552	203/18723	9.29e-08	1.54e-06	130
GO:00066652	Esophagus	ESCC	sphingolipid metabolic process	96/8552	155/18723	3.21e-05	2.66e-04	96
GO:00066721	Esophagus	ESCC	ceramide metabolic process	61/8552	102/18723	2.82e-03	1.19e-02	61
GO:00066431	Liver	HCC	membrane lipid metabolic process	115/7958	203/18723	3.17e-05	3.22e-04	115
GO:0006665	Liver	HCC	sphingolipid metabolic process	85/7958	155/18723	1.27e-03	6.92e-03	85
GO:00066432	Oral cavity	OSCC	membrane lipid metabolic process	111/7305	203/18723	4.02e-06	4.69e-05	111
GO:00066651	Oral cavity	OSCC	sphingolipid metabolic process	84/7305	155/18723	8.64e-05	6.61e-04	84
GO:0006672	Oral cavity	OSCC	ceramide metabolic process	53/7305	102/18723	5.28e-03	2.06e-02	53
GO:000664311	Oral cavity	LP	membrane lipid metabolic process	69/4623	203/18723	1.77e-03	1.34e-02	69

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0407116	Esophagus	ESCC	Sphingolipid signaling pathway	85/4205	121/8465	3.04e-06	1.73e-05	8.84e-06	85
hsa0407117	Esophagus	ESCC	Sphingolipid signaling pathway	85/4205	121/8465	3.04e-06	1.73e-05	8.84e-06	85
hsa040718	Liver	HCC	Sphingolipid signaling pathway	72/4020	121/8465	5.01e-03	1.47e-02	8.18e-03	72
hsa0407111	Liver	HCC	Sphingolipid signaling pathway	72/4020	121/8465	5.01e-03	1.47e-02	8.18e-03	72
hsa0407114	Oral cavity	OSCC	Sphingolipid signaling pathway	82/3704	121/8465	6.97e-08	5.08e-07	2.58e-07	82
hsa0407115	Oral cavity	OSCC	Sphingolipid signaling pathway	82/3704	121/8465	6.97e-08	5.08e-07	2.58e-07	82
hsa0407122	Oral cavity	LP	Sphingolipid signaling pathway	48/2418	121/8465	5.30e-03	2.15e-02	1.39e-02	48
hsa0407132	Oral cavity	LP	Sphingolipid signaling pathway	48/2418	121/8465	5.30e-03	2.15e-02	1.39e-02	48
hsa0407141	Oral cavity	EOLP	Sphingolipid signaling pathway	44/1218	121/8465	1.19e-09	3.51e-08	2.07e-08	44
hsa0407151	Oral cavity	EOLP	Sphingolipid signaling pathway	44/1218	121/8465	1.19e-09	3.51e-08	2.07e-08	44

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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

NSMAF

SNV

Missense_Mutation

c.2162C>A

p.Ser721Tyr

p.S721Y

Q92636

protein_coding

deleterious(0.01)

probably_damaging(0.998)

TCGA-A8-A076-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

NSMAF

SNV

Missense_Mutation

novel

c.2130N>T

p.Leu710Phe

p.L710F

Q92636

protein_coding

tolerated(0.07)

benign(0.017)

TCGA-B6-A1KF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NSMAF

SNV

Missense_Mutation

c.2326N>C

p.Glu776Gln

p.E776Q

Q92636

protein_coding

tolerated(0.29)

benign(0.309)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

NSMAF

SNV

Missense_Mutation

novel

c.1402N>A

p.Asp468Asn

p.D468N

Q92636

protein_coding

tolerated(0.42)

possibly_damaging(0.757)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

NSMAF

SNV

Missense_Mutation

novel

c.2690N>C

p.Gly897Ala

p.G897A

Q92636

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-UU-A93S-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

NSMAF

insertion

In_Frame_Ins

novel

c.1411_1412insACAGATACCTGTTTTTGCTGATGTTGTTTGTTTTCAGCTATAGAC

p.Thr471delinsAsnArgTyrLeuPheLeuLeuMetLeuPheValPheSerTyrArgPro

p.T471delinsNRYLFLLMLFVFSYRP

Q92636

protein_coding

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

NSMAF

insertion

Frame_Shift_Ins

novel

c.1822_1823insGA

p.Thr608ArgfsTer30

p.T608Rfs*30

Q92636

protein_coding

TCGA-B6-A0I9-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

NSMAF

insertion

Frame_Shift_Ins

novel

c.1820_1821insGGGATTAAACTGTTTTAAGCTGAGT

p.Ile607MetfsTer14

p.I607Mfs*14

Q92636

protein_coding

TCGA-B6-A0I9-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

NSMAF

insertion

Frame_Shift_Ins

novel

c.1289_1290insCGGCCTCCCAAAGTGCTGGGATTACAGG

p.Phe431GlyfsTer14

p.F431Gfs*14

Q92636

protein_coding

TCGA-BH-A0EE-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

docetaxel

NSMAF

SNV

Missense_Mutation

c.377G>C

p.Arg126Thr

p.R126T

Q92636

protein_coding

tolerated(0.47)

benign(0)

TCGA-EK-A2R8-01

Cervix

cervical & endocervical cancer

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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