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: SPTLC2

Gene summary for SPTLC2

Gene summary.

Gene information	Species	Human
	Gene symbol	SPTLC2
	Gene ID	9517
	Gene name	serine palmitoyltransferase long chain base subunit 2
	Gene Alias	HSN1C
	Cytomap	14q24.3
	Gene Type	protein-coding
	GO ID	GO:0006066
	UniProtAcc	A0A024R6H1

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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
9517	SPTLC2	P44T-E	Human	Esophagus	ESCC	6.52e-12	3.18e-01	0.1096
9517	SPTLC2	P47T-E	Human	Esophagus	ESCC	2.11e-12	2.97e-01	0.1067
9517	SPTLC2	P48T-E	Human	Esophagus	ESCC	1.74e-08	1.69e-01	0.0959
9517	SPTLC2	P49T-E	Human	Esophagus	ESCC	6.37e-21	2.13e+00	0.1768
9517	SPTLC2	P52T-E	Human	Esophagus	ESCC	2.05e-14	4.24e-01	0.1555
9517	SPTLC2	P54T-E	Human	Esophagus	ESCC	7.18e-28	5.81e-01	0.0975
9517	SPTLC2	P56T-E	Human	Esophagus	ESCC	7.28e-06	5.38e-01	0.1613
9517	SPTLC2	P57T-E	Human	Esophagus	ESCC	9.05e-23	4.31e-01	0.0926
9517	SPTLC2	P61T-E	Human	Esophagus	ESCC	3.08e-31	8.95e-01	0.099
9517	SPTLC2	P62T-E	Human	Esophagus	ESCC	2.05e-20	4.59e-01	0.1302
9517	SPTLC2	P65T-E	Human	Esophagus	ESCC	6.28e-24	5.67e-01	0.0978
9517	SPTLC2	P74T-E	Human	Esophagus	ESCC	1.24e-22	6.22e-01	0.1479
9517	SPTLC2	P75T-E	Human	Esophagus	ESCC	1.83e-40	8.36e-01	0.1125
9517	SPTLC2	P76T-E	Human	Esophagus	ESCC	1.14e-17	2.36e-01	0.1207
9517	SPTLC2	P79T-E	Human	Esophagus	ESCC	1.05e-32	6.16e-01	0.1154
9517	SPTLC2	P80T-E	Human	Esophagus	ESCC	1.27e-23	7.98e-01	0.155
9517	SPTLC2	P82T-E	Human	Esophagus	ESCC	4.34e-10	5.08e-01	0.1072
9517	SPTLC2	P83T-E	Human	Esophagus	ESCC	1.35e-30	8.84e-01	0.1738
9517	SPTLC2	P84T-E	Human	Esophagus	ESCC	1.47e-08	7.01e-01	0.0933
9517	SPTLC2	P89T-E	Human	Esophagus	ESCC	2.61e-05	6.01e-01	0.1752

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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
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:0009896	Colorectum	AD	positive regulation of catabolic process	180/3918	492/18723	4.33e-16	1.94e-13	180
GO:0031331	Colorectum	AD	positive regulation of cellular catabolic process	156/3918	427/18723	4.68e-14	1.05e-11	156
GO:0010506	Colorectum	AD	regulation of autophagy	111/3918	317/18723	3.57e-09	2.35e-07	111
GO:0016236	Colorectum	AD	macroautophagy	103/3918	291/18723	6.76e-09	4.15e-07	103
GO:0006066	Colorectum	AD	alcohol metabolic process	106/3918	353/18723	3.02e-05	5.57e-04	106
GO:0061912	Colorectum	AD	selective autophagy	29/3918	68/18723	4.20e-05	7.39e-04	29
GO:0016241	Colorectum	AD	regulation of macroautophagy	50/3918	141/18723	4.55e-05	7.92e-04	50
GO:0010508	Colorectum	AD	positive regulation of autophagy	43/3918	124/18723	2.64e-04	3.27e-03	43
GO:0006644	Colorectum	AD	phospholipid metabolic process	101/3918	383/18723	5.80e-03	3.67e-02	101
GO:00098962	Colorectum	MSS	positive regulation of catabolic process	163/3467	492/18723	3.10e-15	9.22e-13	163
GO:00313312	Colorectum	MSS	positive regulation of cellular catabolic process	140/3467	427/18723	7.02e-13	1.33e-10	140
GO:00162362	Colorectum	MSS	macroautophagy	93/3467	291/18723	2.08e-08	1.17e-06	93
GO:00105062	Colorectum	MSS	regulation of autophagy	95/3467	317/18723	4.36e-07	1.71e-05	95
GO:00619122	Colorectum	MSS	selective autophagy	27/3467	68/18723	3.68e-05	7.09e-04	27
GO:00162412	Colorectum	MSS	regulation of macroautophagy	44/3467	141/18723	1.88e-04	2.64e-03	44
GO:00060662	Colorectum	MSS	alcohol metabolic process	92/3467	353/18723	2.57e-04	3.46e-03	92
GO:00098964	Colorectum	FAP	positive regulation of catabolic process	126/2622	492/18723	3.76e-12	2.56e-09	126
GO:00313314	Colorectum	FAP	positive regulation of cellular catabolic process	110/2622	427/18723	6.09e-11	2.19e-08	110
GO:00105063	Colorectum	FAP	regulation of autophagy	80/2622	317/18723	6.43e-08	4.54e-06	80
GO:00162363	Colorectum	FAP	macroautophagy	70/2622	291/18723	2.73e-06	1.02e-04	70

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa04071	Colorectum	AD	Sphingolipid signaling pathway	43/2092	121/8465	4.83e-03	2.28e-02	1.45e-02	43
hsa040711	Colorectum	AD	Sphingolipid signaling pathway	43/2092	121/8465	4.83e-03	2.28e-02	1.45e-02	43
hsa040714	Colorectum	FAP	Sphingolipid signaling pathway	34/1404	121/8465	9.53e-04	5.22e-03	3.17e-03	34
hsa040715	Colorectum	FAP	Sphingolipid signaling pathway	34/1404	121/8465	9.53e-04	5.22e-03	3.17e-03	34
hsa040716	Colorectum	CRC	Sphingolipid signaling pathway	30/1091	121/8465	2.49e-04	3.09e-03	2.09e-03	30
hsa040717	Colorectum	CRC	Sphingolipid signaling pathway	30/1091	121/8465	2.49e-04	3.09e-03	2.09e-03	30
hsa0407116	Esophagus	ESCC	Sphingolipid signaling pathway	85/4205	121/8465	3.04e-06	1.73e-05	8.84e-06	85
hsa006003	Esophagus	ESCC	Sphingolipid metabolism	36/4205	53/8465	5.41e-03	1.36e-02	6.99e-03	36
hsa0407117	Esophagus	ESCC	Sphingolipid signaling pathway	85/4205	121/8465	3.04e-06	1.73e-05	8.84e-06	85
hsa0060012	Esophagus	ESCC	Sphingolipid metabolism	36/4205	53/8465	5.41e-03	1.36e-02	6.99e-03	36
hsa040718	Liver	HCC	Sphingolipid signaling pathway	72/4020	121/8465	5.01e-03	1.47e-02	8.18e-03	72
hsa00600	Liver	HCC	Sphingolipid metabolism	34/4020	53/8465	1.06e-02	2.71e-02	1.51e-02	34
hsa0407111	Liver	HCC	Sphingolipid signaling pathway	72/4020	121/8465	5.01e-03	1.47e-02	8.18e-03	72
hsa006001	Liver	HCC	Sphingolipid metabolism	34/4020	53/8465	1.06e-02	2.71e-02	1.51e-02	34
hsa040719	Lung	IAC	Sphingolipid signaling pathway	28/1053	121/8465	7.30e-04	6.08e-03	4.04e-03	28
hsa0407112	Lung	IAC	Sphingolipid signaling pathway	28/1053	121/8465	7.30e-04	6.08e-03	4.04e-03	28
hsa0407114	Oral cavity	OSCC	Sphingolipid signaling pathway	82/3704	121/8465	6.97e-08	5.08e-07	2.58e-07	82
hsa006002	Oral cavity	OSCC	Sphingolipid metabolism	33/3704	53/8465	5.00e-03	1.20e-02	6.13e-03	33
hsa0407115	Oral cavity	OSCC	Sphingolipid signaling pathway	82/3704	121/8465	6.97e-08	5.08e-07	2.58e-07	82
hsa0060011	Oral cavity	OSCC	Sphingolipid metabolism	33/3704	53/8465	5.00e-03	1.20e-02	6.13e-03	33

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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

SPTLC2

SNV

Missense_Mutation

novel

c.637N>A

p.Leu213Met

p.L213M

O15270

protein_coding

tolerated(0.11)

benign(0.213)

TCGA-A1-A0SI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SPTLC2

SNV

Missense_Mutation

c.1627N>T

p.Arg543Trp

p.R543W

O15270

protein_coding

deleterious(0)

possibly_damaging(0.634)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SPTLC2

SNV

Missense_Mutation

novel

c.841A>G

p.Lys281Glu

p.K281E

O15270

protein_coding

deleterious(0.03)

possibly_damaging(0.479)

TCGA-AR-A5QQ-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

carboplatin

SPTLC2

SNV

Missense_Mutation

c.509N>G

p.Val170Gly

p.V170G

O15270

protein_coding

deleterious(0)

possibly_damaging(0.71)

TCGA-BH-A0DL-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

SPTLC2

SNV

Missense_Mutation

c.1363N>C

p.Glu455Gln

p.E455Q

O15270

protein_coding

tolerated(0.5)

benign(0.129)

TCGA-BH-A0DZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

docetaxel

SPTLC2

SNV

Missense_Mutation

c.1588G>A

p.Glu530Lys

p.E530K

O15270

protein_coding

tolerated(0.12)

benign(0.077)

TCGA-D8-A27G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SPTLC2

SNV

Missense_Mutation

novel

c.1489N>A

p.Gly497Arg

p.G497R

O15270

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SPTLC2

SNV

Missense_Mutation

rs763898397

c.1628N>A

p.Arg543Gln

p.R543Q

O15270

protein_coding

deleterious(0.04)

benign(0.086)

TCGA-C5-A1BM-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

SPTLC2

deletion

Frame_Shift_Del

novel

c.395_407delACAACTGGAATCG

p.Asp132GlyfsTer31

p.D132Gfs*31

O15270

protein_coding

TCGA-FU-A23L-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SPTLC2

SNV

Missense_Mutation

c.331T>G

p.Phe111Val

p.F111V

O15270

protein_coding

deleterious(0)

probably_damaging(0.945)

TCGA-A6-3809-01

Colorectum

colon adenocarcinoma

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
9517	SPTLC2	ENZYME	inhibitor	178103276	MYRIOCIN

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