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: SULF2

Gene summary for SULF2

Gene summary.

Gene information	Species	Human
	Gene symbol	SULF2
	Gene ID	55959
	Gene name	sulfatase 2
	Gene Alias	HSULF-2
	Cytomap	20q13.12
	Gene Type	protein-coding
	GO ID	GO:0001501
	UniProtAcc	Q8IWU5

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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
55959	SULF2	HTA11_3410_2000001011	Human	Colorectum	AD	1.79e-10	-5.02e-01	0.0155
55959	SULF2	HTA11_866_3004761011	Human	Colorectum	AD	5.22e-06	-4.10e-01	0.096
55959	SULF2	HTA11_10711_2000001011	Human	Colorectum	AD	3.83e-02	-4.27e-01	0.0338
55959	SULF2	HTA11_7696_3000711011	Human	Colorectum	AD	1.17e-04	-3.52e-01	0.0674
55959	SULF2	HTA11_99999970781_79442	Human	Colorectum	MSS	1.81e-08	-3.39e-01	0.294
55959	SULF2	F007	Human	Colorectum	FAP	3.62e-06	-4.72e-01	0.1176
55959	SULF2	A002-C-010	Human	Colorectum	FAP	1.35e-19	-4.65e-01	0.242
55959	SULF2	A001-C-207	Human	Colorectum	FAP	5.79e-14	-5.44e-01	0.1278
55959	SULF2	A015-C-203	Human	Colorectum	FAP	2.96e-26	-5.25e-01	-0.1294
55959	SULF2	A015-C-204	Human	Colorectum	FAP	1.02e-08	-4.27e-01	-0.0228
55959	SULF2	A014-C-040	Human	Colorectum	FAP	7.68e-05	-5.69e-01	-0.1184
55959	SULF2	A002-C-201	Human	Colorectum	FAP	6.40e-15	-4.68e-01	0.0324
55959	SULF2	A002-C-203	Human	Colorectum	FAP	9.02e-17	-4.98e-01	0.2786
55959	SULF2	A001-C-119	Human	Colorectum	FAP	1.90e-06	-4.34e-01	-0.1557
55959	SULF2	A001-C-108	Human	Colorectum	FAP	4.46e-21	-5.13e-01	-0.0272
55959	SULF2	A002-C-021	Human	Colorectum	FAP	1.99e-02	-3.05e-01	0.1171
55959	SULF2	A002-C-205	Human	Colorectum	FAP	1.46e-21	-5.58e-01	-0.1236
55959	SULF2	A001-C-104	Human	Colorectum	FAP	2.24e-10	-4.45e-01	0.0184
55959	SULF2	A015-C-005	Human	Colorectum	FAP	2.01e-11	-5.06e-01	-0.0336
55959	SULF2	A015-C-006	Human	Colorectum	FAP	1.98e-09	-3.21e-01	-0.0994

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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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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
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:006100818	Oral cavity	OSCC	hepaticobiliary system development	88/7305	150/18723	8.13e-07	1.12e-05	88
GO:003011110	Oral cavity	OSCC	regulation of Wnt signaling pathway	165/7305	328/18723	1.87e-05	1.80e-04	165
GO:005067310	Oral cavity	OSCC	epithelial cell proliferation	212/7305	437/18723	2.82e-05	2.61e-04	212
GO:00902639	Oral cavity	OSCC	positive regulation of canonical Wnt signaling pathway	62/7305	106/18723	3.72e-05	3.31e-04	62
GO:006082810	Oral cavity	OSCC	regulation of canonical Wnt signaling pathway	128/7305	253/18723	1.11e-04	8.16e-04	128
GO:00091001	Oral cavity	OSCC	glycoprotein metabolic process	185/7305	387/18723	2.37e-04	1.54e-03	185
GO:00311008	Oral cavity	OSCC	animal organ regeneration	45/7305	76/18723	2.83e-04	1.79e-03	45
GO:006007010	Oral cavity	OSCC	canonical Wnt signaling pathway	148/7305	303/18723	2.89e-04	1.82e-03	148
GO:00301983	Oral cavity	OSCC	extracellular matrix organization	146/7305	301/18723	4.67e-04	2.77e-03	146
GO:00452293	Oral cavity	OSCC	external encapsulating structure organization	147/7305	304/18723	5.30e-04	3.08e-03	147
GO:00430623	Oral cavity	OSCC	extracellular structure organization	146/7305	302/18723	5.59e-04	3.23e-03	146
GO:005067810	Oral cavity	OSCC	regulation of epithelial cell proliferation	180/7305	381/18723	5.88e-04	3.35e-03	180
GO:00016558	Oral cavity	OSCC	urogenital system development	160/7305	338/18723	1.03e-03	5.31e-03	160
GO:00301779	Oral cavity	OSCC	positive regulation of Wnt signaling pathway	73/7305	140/18723	1.06e-03	5.46e-03	73
GO:002261214	Oral cavity	OSCC	gland morphogenesis	62/7305	118/18723	1.91e-03	8.94e-03	62
GO:000181910	Oral cavity	OSCC	positive regulation of cytokine production	213/7305	467/18723	1.93e-03	8.96e-03	213
GO:00974219	Oral cavity	OSCC	liver regeneration	22/7305	35/18723	3.65e-03	1.51e-02	22
GO:00603484	Oral cavity	OSCC	bone development	99/7305	205/18723	4.13e-03	1.68e-02	99
GO:000188919	Oral cavity	LP	liver development	62/4623	147/18723	2.32e-06	5.14e-05	62
GO:0048732110	Oral cavity	LP	gland development	149/4623	436/18723	4.51e-06	9.17e-05	149

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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

SULF2

SNV

Missense_Mutation

rs367871609

c.518N>T

p.Thr173Met

p.T173M

Q8IWU5

protein_coding

deleterious(0)

probably_damaging(0.995)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SULF2

SNV

Missense_Mutation

c.1203G>C

p.Leu401Phe

p.L401F

Q8IWU5

protein_coding

tolerated(0.21)

benign(0.035)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SULF2

SNV

Missense_Mutation

rs149787530

c.1492G>A

p.Gly498Arg

p.G498R

Q8IWU5

protein_coding

tolerated(0.48)

benign(0.009)

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

SULF2

SNV

Missense_Mutation

rs781507832

c.1181N>A

p.Arg394Gln

p.R394Q

Q8IWU5

protein_coding

tolerated(0.08)

benign(0.017)

TCGA-BH-A0HI-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

SULF2

SNV

Missense_Mutation

c.955N>A

p.Gly319Ser

p.G319S

Q8IWU5

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-D8-A1XY-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

tamoxiphen

SULF2

insertion

Frame_Shift_Ins

novel

c.454_455insTCCAGTTTGGGGTTATTACAAATAGCGCTGCTGA

p.Tyr152PhefsTer25

p.Y152Ffs*25

Q8IWU5

protein_coding

TCGA-AN-A03X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SULF2

insertion

Frame_Shift_Ins

novel

c.511_512insGCCGGGTGTGTTGGCACATGCCTGTGGACCCAGCTACTAGAGAG

p.Asn171SerfsTer24

p.N171Sfs*24

Q8IWU5

protein_coding

TCGA-AN-A0FX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SULF2

SNV

Missense_Mutation

novel

c.502N>T

p.Arg168Cys

p.R168C

Q8IWU5

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SULF2

SNV

Missense_Mutation

novel

c.1225N>T

p.Arg409Trp

p.R409W

Q8IWU5

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-EA-A410-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SULF2

SNV

Missense_Mutation

c.439N>A

p.Glu147Lys

p.E147K

Q8IWU5

protein_coding

tolerated(0.07)

probably_damaging(0.998)

TCGA-EK-A2PG-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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