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: SMOX

Gene summary for SMOX

Gene summary.

Gene information	Species	Human
	Gene symbol	SMOX
	Gene ID	54498
	Gene name	spermine oxidase
	Gene Alias	C20orf16
	Cytomap	20p13
	Gene Type	protein-coding
	GO ID	GO:0006576
	UniProtAcc	Q9NWM0

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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
54498	SMOX	LZE4T	Human	Esophagus	ESCC	1.07e-03	1.29e-01	0.0811
54498	SMOX	LZE8T	Human	Esophagus	ESCC	1.62e-03	6.07e-02	0.067
54498	SMOX	LZE24T	Human	Esophagus	ESCC	1.22e-07	2.71e-01	0.0596
54498	SMOX	P2T-E	Human	Esophagus	ESCC	1.32e-16	3.62e-01	0.1177
54498	SMOX	P4T-E	Human	Esophagus	ESCC	7.03e-12	4.45e-01	0.1323
54498	SMOX	P5T-E	Human	Esophagus	ESCC	1.34e-02	6.54e-03	0.1327
54498	SMOX	P8T-E	Human	Esophagus	ESCC	8.03e-13	2.55e-01	0.0889
54498	SMOX	P9T-E	Human	Esophagus	ESCC	4.46e-08	1.50e-01	0.1131
54498	SMOX	P10T-E	Human	Esophagus	ESCC	2.74e-09	2.03e-01	0.116
54498	SMOX	P11T-E	Human	Esophagus	ESCC	2.09e-04	2.65e-01	0.1426
54498	SMOX	P12T-E	Human	Esophagus	ESCC	4.91e-25	4.90e-01	0.1122
54498	SMOX	P15T-E	Human	Esophagus	ESCC	3.02e-14	2.22e-01	0.1149
54498	SMOX	P16T-E	Human	Esophagus	ESCC	1.32e-27	5.94e-01	0.1153
54498	SMOX	P20T-E	Human	Esophagus	ESCC	1.36e-08	1.55e-01	0.1124
54498	SMOX	P21T-E	Human	Esophagus	ESCC	1.42e-06	2.04e-01	0.1617
54498	SMOX	P22T-E	Human	Esophagus	ESCC	4.82e-10	1.18e-01	0.1236
54498	SMOX	P23T-E	Human	Esophagus	ESCC	4.12e-10	3.11e-01	0.108
54498	SMOX	P24T-E	Human	Esophagus	ESCC	9.53e-06	1.68e-01	0.1287
54498	SMOX	P26T-E	Human	Esophagus	ESCC	8.20e-59	1.19e+00	0.1276
54498	SMOX	P27T-E	Human	Esophagus	ESCC	1.67e-18	3.80e-01	0.1055

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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
Liver		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
Prostate		BPH: Benign Prostatic Hyperplasia

∗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:000941020	Esophagus	ESCC	response to xenobiotic stimulus	253/8552	462/18723	4.55e-05	3.58e-04	253
GO:000941012	Liver	Cirrhotic	response to xenobiotic stimulus	165/4634	462/18723	6.82e-08	2.09e-06	165
GO:00714661	Liver	Cirrhotic	cellular response to xenobiotic stimulus	66/4634	177/18723	1.34e-04	1.31e-03	66
GO:0006595	Liver	Cirrhotic	polyamine metabolic process	12/4634	18/18723	2.07e-04	1.90e-03	12
GO:00065962	Liver	Cirrhotic	polyamine biosynthetic process	10/4634	14/18723	3.11e-04	2.72e-03	10
GO:00424021	Liver	Cirrhotic	cellular biogenic amine catabolic process	15/4634	27/18723	5.96e-04	4.63e-03	15
GO:000680511	Liver	Cirrhotic	xenobiotic metabolic process	43/4634	111/18723	7.51e-04	5.54e-03	43
GO:0044106	Liver	Cirrhotic	cellular amine metabolic process	43/4634	113/18723	1.15e-03	7.83e-03	43
GO:00093101	Liver	Cirrhotic	amine catabolic process	15/4634	29/18723	1.59e-03	1.03e-02	15
GO:0006576	Liver	Cirrhotic	cellular biogenic amine metabolic process	38/4634	101/18723	2.72e-03	1.59e-02	38
GO:0009308	Liver	Cirrhotic	amine metabolic process	43/4634	118/18723	3.03e-03	1.72e-02	43
GO:000941022	Liver	HCC	response to xenobiotic stimulus	248/7958	462/18723	6.47e-07	1.02e-05	248
GO:00065961	Liver	HCC	polyamine biosynthetic process	12/7958	14/18723	1.17e-03	6.54e-03	12
GO:00065951	Liver	HCC	polyamine metabolic process	14/7958	18/18723	2.57e-03	1.23e-02	14
GO:00714662	Liver	HCC	cellular response to xenobiotic stimulus	93/7958	177/18723	4.35e-03	1.89e-02	93
GO:000941018	Oral cavity	OSCC	response to xenobiotic stimulus	222/7305	462/18723	4.00e-05	3.48e-04	222
GO:00065954	Oral cavity	OSCC	polyamine metabolic process	13/7305	18/18723	4.45e-03	1.79e-02	13
GO:00065965	Oral cavity	OSCC	polyamine biosynthetic process	10/7305	14/18723	1.44e-02	4.69e-02	10
GO:000659512	Oral cavity	LP	polyamine metabolic process	13/4623	18/18723	2.94e-05	4.58e-04	13
GO:000659612	Oral cavity	LP	polyamine biosynthetic process	10/4623	14/18723	3.05e-04	3.12e-03	10

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa00410	Liver	Cirrhotic	beta-Alanine metabolism	18/2530	31/8465	1.00e-03	5.57e-03	3.43e-03	18
hsa003308	Liver	Cirrhotic	Arginine and proline metabolism	25/2530	50/8465	2.18e-03	9.41e-03	5.80e-03	25
hsa004101	Liver	Cirrhotic	beta-Alanine metabolism	18/2530	31/8465	1.00e-03	5.57e-03	3.43e-03	18
hsa0033011	Liver	Cirrhotic	Arginine and proline metabolism	25/2530	50/8465	2.18e-03	9.41e-03	5.80e-03	25
hsa0033021	Liver	HCC	Arginine and proline metabolism	33/4020	50/8465	6.28e-03	1.77e-02	9.83e-03	33
hsa004102	Liver	HCC	beta-Alanine metabolism	22/4020	31/8465	6.93e-03	1.92e-02	1.07e-02	22
hsa0033031	Liver	HCC	Arginine and proline metabolism	33/4020	50/8465	6.28e-03	1.77e-02	9.83e-03	33
hsa004103	Liver	HCC	beta-Alanine metabolism	22/4020	31/8465	6.93e-03	1.92e-02	1.07e-02	22
hsa0033010	Oral cavity	OSCC	Arginine and proline metabolism	30/3704	50/8465	1.50e-02	3.26e-02	1.66e-02	30
hsa0033013	Oral cavity	OSCC	Arginine and proline metabolism	30/3704	50/8465	1.50e-02	3.26e-02	1.66e-02	30
hsa0033023	Oral cavity	LP	Arginine and proline metabolism	26/2418	50/8465	3.94e-04	2.08e-03	1.34e-03	26
hsa0033033	Oral cavity	LP	Arginine and proline metabolism	26/2418	50/8465	3.94e-04	2.08e-03	1.34e-03	26
hsa003309	Prostate	BPH	Arginine and proline metabolism	18/1718	50/8465	7.17e-03	2.32e-02	1.43e-02	18
hsa0033012	Prostate	BPH	Arginine and proline metabolism	18/1718	50/8465	7.17e-03	2.32e-02	1.43e-02	18
hsa0033022	Prostate	Tumor	Arginine and proline metabolism	19/1791	50/8465	4.73e-03	1.67e-02	1.03e-02	19
hsa004104	Prostate	Tumor	beta-Alanine metabolism	13/1791	31/8465	7.13e-03	2.34e-02	1.45e-02	13
hsa0033032	Prostate	Tumor	Arginine and proline metabolism	19/1791	50/8465	4.73e-03	1.67e-02	1.03e-02	19
hsa0041011	Prostate	Tumor	beta-Alanine metabolism	13/1791	31/8465	7.13e-03	2.34e-02	1.45e-02	13

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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

SMOX

SNV

Missense_Mutation

rs775564398

c.1591N>A

p.Pro531Thr

p.P531T

Q9NWM0

protein_coding

deleterious_low_confidence(0.04)

benign(0.003)

TCGA-AQ-A1H2-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

herceptin

SMOX

SNV

Missense_Mutation

rs775564398

c.1591N>A

p.Pro531Thr

p.P531T

Q9NWM0

protein_coding

deleterious_low_confidence(0.04)

benign(0.003)

TCGA-AR-A24P-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SMOX

SNV

Missense_Mutation

rs375716040

c.358N>A

p.Val120Met

p.V120M

Q9NWM0

protein_coding

tolerated(0.06)

probably_damaging(0.999)

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

SMOX

insertion

In_Frame_Ins

novel

c.1341_1342insCTCCAGCGA

p.Ile447_Cys448insLeuGlnArg

p.I447_C448insLQR

Q9NWM0

protein_coding

TCGA-A8-A07U-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

SMOX

insertion

Frame_Shift_Ins

novel

c.1344_1345insCAGGGCCTTGGATCAAGTCC

p.Thr449GlnfsTer98

p.T449Qfs*98

Q9NWM0

protein_coding

TCGA-A8-A07U-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

SMOX

SNV

Missense_Mutation

rs370515510

c.386N>A

p.Arg129His

p.R129H

Q9NWM0

protein_coding

tolerated(0.11)

benign(0)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SMOX

SNV

Missense_Mutation

novel

c.1138N>A

p.Glu380Lys

p.E380K

Q9NWM0

protein_coding

deleterious(0.01)

benign(0.423)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SMOX

SNV

Missense_Mutation

c.59N>A

p.Arg20Gln

p.R20Q

Q9NWM0

protein_coding

deleterious(0.04)

benign(0.375)

TCGA-C5-A3HF-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SMOX

SNV

Missense_Mutation

rs752255111

c.809N>T

p.Ser270Leu

p.S270L

Q9NWM0

protein_coding

tolerated(0.65)

benign(0.097)

TCGA-IR-A3LK-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

SMOX

SNV

Missense_Mutation

novel

c.290N>A

p.Gly97Asp

p.G97D

Q9NWM0

protein_coding

tolerated(0.06)

probably_damaging(0.997)

TCGA-MA-AA42-01

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
54498	SMOX	ENZYME, DRUGGABLE GENOME		DFMO		10409651
54498	SMOX	ENZYME, DRUGGABLE GENOME		AZASERINE	AZASERINE	7899459
54498	SMOX	ENZYME, DRUGGABLE GENOME		ENZYME INHIBITOR		6885895

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