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: THBS2

Gene summary for THBS2

Gene summary.

Gene information	Species	Human
	Gene symbol	THBS2
	Gene ID	7058
	Gene name	thrombospondin 2
	Gene Alias	TSP2
	Cytomap	6q27
	Gene Type	protein-coding
	GO ID	GO:0001525
	UniProtAcc	P35442

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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
7058	THBS2	LZE7T	Human	Esophagus	ESCC	2.46e-12	6.48e-02	0.0667
7058	THBS2	P2T-E	Human	Esophagus	ESCC	1.54e-03	-1.91e-01	0.1177
7058	THBS2	P8T-E	Human	Esophagus	ESCC	2.71e-02	-1.80e-01	0.0889
7058	THBS2	P11T-E	Human	Esophagus	ESCC	1.49e-02	9.12e-01	0.1426
7058	THBS2	P12T-E	Human	Esophagus	ESCC	3.77e-05	-2.05e-01	0.1122
7058	THBS2	P20T-E	Human	Esophagus	ESCC	2.77e-02	2.08e-01	0.1124
7058	THBS2	P26T-E	Human	Esophagus	ESCC	5.88e-05	-1.82e-01	0.1276
7058	THBS2	P37T-E	Human	Esophagus	ESCC	2.65e-44	1.60e+00	0.1371
7058	THBS2	P48T-E	Human	Esophagus	ESCC	1.12e-04	-1.98e-01	0.0959
7058	THBS2	P76T-E	Human	Esophagus	ESCC	1.20e-04	4.94e-01	0.1207
7058	THBS2	P107T-E	Human	Esophagus	ESCC	2.64e-02	-1.99e-01	0.171
7058	THBS2	P127T-E	Human	Esophagus	ESCC	1.76e-02	-1.62e-01	0.0826
7058	THBS2	C04	Human	Oral cavity	OSCC	1.54e-15	8.04e-01	0.2633
7058	THBS2	C21	Human	Oral cavity	OSCC	1.88e-25	8.53e-01	0.2678
7058	THBS2	C51	Human	Oral cavity	OSCC	5.58e-41	1.88e+00	0.2674
7058	THBS2	C07	Human	Oral cavity	OSCC	5.72e-03	1.06e+00	0.2491
7058	THBS2	LP15	Human	Oral cavity	LP	8.27e-07	1.73e+00	0.2174
7058	THBS2	NEOLP-1	Human	Oral cavity	NEOLP	1.07e-13	5.66e-01	-0.0194
7058	THBS2	SYSMH2	Human	Oral cavity	OSCC	2.26e-11	4.18e-01	0.2326
7058	THBS2	SYSMH3	Human	Oral cavity	OSCC	5.70e-25	9.46e-01	0.2442

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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
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:003432918	Esophagus	ESCC	cell junction assembly	227/8552	420/18723	3.06e-04	1.83e-03	227
GO:00519606	Esophagus	ESCC	regulation of nervous system development	237/8552	443/18723	5.02e-04	2.78e-03	237
GO:00519625	Esophagus	ESCC	positive regulation of nervous system development	149/8552	272/18723	1.50e-03	7.06e-03	149
GO:190188810	Esophagus	ESCC	regulation of cell junction assembly	109/8552	204/18723	1.53e-02	4.96e-02	109
GO:00519624	Oral cavity	OSCC	positive regulation of nervous system development	135/7305	272/18723	2.20e-04	1.44e-03	135
GO:00519605	Oral cavity	OSCC	regulation of nervous system development	205/7305	443/18723	9.80e-04	5.11e-03	205
GO:003432916	Oral cavity	OSCC	cell junction assembly	190/7305	420/18723	4.99e-03	1.96e-02	190
GO:003432923	Oral cavity	NEOLP	cell junction assembly	88/2005	420/18723	4.18e-10	3.44e-08	88
GO:190188814	Oral cavity	NEOLP	regulation of cell junction assembly	47/2005	204/18723	2.82e-07	8.96e-06	47
GO:190134213	Oral cavity	NEOLP	regulation of vasculature development	59/2005	348/18723	2.42e-04	2.52e-03	59
GO:00457655	Oral cavity	NEOLP	regulation of angiogenesis	58/2005	342/18723	2.70e-04	2.72e-03	58
GO:005196212	Oral cavity	NEOLP	positive regulation of nervous system development	47/2005	272/18723	6.49e-04	5.47e-03	47
GO:005196012	Oral cavity	NEOLP	regulation of nervous system development	68/2005	443/18723	1.46e-03	1.03e-02	68
GO:003432919	Skin	AK	cell junction assembly	86/1910	420/18723	1.95e-10	2.68e-08	86
GO:190188815	Skin	AK	regulation of cell junction assembly	43/1910	204/18723	2.99e-06	7.93e-05	43
GO:00508088	Skin	AK	synapse organization	71/1910	426/18723	2.21e-05	4.07e-04	71
GO:00519607	Skin	AK	regulation of nervous system development	72/1910	443/18723	4.53e-05	7.11e-04	72
GO:00519626	Skin	AK	positive regulation of nervous system development	49/1910	272/18723	5.65e-05	8.50e-04	49
GO:00508031	Skin	AK	regulation of synapse structure or activity	38/1910	218/18723	7.06e-04	6.01e-03	38
GO:00508073	Skin	AK	regulation of synapse organization	37/1910	211/18723	7.35e-04	6.20e-03	37

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0516510	Esophagus	ESCC	Human papillomavirus infection	215/4205	331/8465	7.86e-09	7.12e-08	3.65e-08	215
hsa0414530	Esophagus	ESCC	Phagosome	100/4205	152/8465	3.81e-05	1.72e-04	8.82e-05	100
hsa0451020	Esophagus	ESCC	Focal adhesion	127/4205	203/8465	1.25e-04	4.99e-04	2.56e-04	127
hsa041517	Esophagus	ESCC	PI3K-Akt signaling pathway	197/4205	354/8465	1.24e-02	2.83e-02	1.45e-02	197
hsa0516515	Esophagus	ESCC	Human papillomavirus infection	215/4205	331/8465	7.86e-09	7.12e-08	3.65e-08	215
hsa04145114	Esophagus	ESCC	Phagosome	100/4205	152/8465	3.81e-05	1.72e-04	8.82e-05	100
hsa04510111	Esophagus	ESCC	Focal adhesion	127/4205	203/8465	1.25e-04	4.99e-04	2.56e-04	127
hsa0415114	Esophagus	ESCC	PI3K-Akt signaling pathway	197/4205	354/8465	1.24e-02	2.83e-02	1.45e-02	197
hsa051659	Oral cavity	OSCC	Human papillomavirus infection	200/3704	331/8465	3.83e-10	4.93e-09	2.51e-09	200
hsa0451019	Oral cavity	OSCC	Focal adhesion	128/3704	203/8465	1.71e-08	1.63e-07	8.31e-08	128
hsa0414528	Oral cavity	OSCC	Phagosome	88/3704	152/8465	2.83e-04	9.13e-04	4.65e-04	88
hsa041516	Oral cavity	OSCC	PI3K-Akt signaling pathway	185/3704	354/8465	6.26e-04	1.86e-03	9.49e-04	185
hsa0516514	Oral cavity	OSCC	Human papillomavirus infection	200/3704	331/8465	3.83e-10	4.93e-09	2.51e-09	200
hsa04510110	Oral cavity	OSCC	Focal adhesion	128/3704	203/8465	1.71e-08	1.63e-07	8.31e-08	128
hsa04145113	Oral cavity	OSCC	Phagosome	88/3704	152/8465	2.83e-04	9.13e-04	4.65e-04	88
hsa0415113	Oral cavity	OSCC	PI3K-Akt signaling pathway	185/3704	354/8465	6.26e-04	1.86e-03	9.49e-04	185
hsa0414529	Oral cavity	LP	Phagosome	73/2418	152/8465	2.37e-07	3.29e-06	2.12e-06	73
hsa0516523	Oral cavity	LP	Human papillomavirus infection	121/2418	331/8465	8.00e-04	3.86e-03	2.49e-03	121
hsa0414536	Oral cavity	LP	Phagosome	73/2418	152/8465	2.37e-07	3.29e-06	2.12e-06	73
hsa0516533	Oral cavity	LP	Human papillomavirus infection	121/2418	331/8465	8.00e-04	3.86e-03	2.49e-03	121

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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
THBS2	SDC4	THBS2_SDC4	THBS	Breast	ADJ
THBS2	CD47	THBS2_CD47	THBS	Breast	ADJ
THBS2	SDC1	THBS2_SDC1	THBS	Breast	DCIS
THBS2	SDC4	THBS2_SDC4	THBS	Breast	DCIS
THBS2	CD36	THBS2_CD36	THBS	Breast	DCIS
THBS2	CD47	THBS2_CD47	THBS	Breast	DCIS
THBS2	SDC1	THBS2_SDC1	THBS	Breast	Healthy
THBS2	SDC4	THBS2_SDC4	THBS	Breast	Healthy
THBS2	CD36	THBS2_CD36	THBS	Breast	Healthy
THBS2	CD47	THBS2_CD47	THBS	Breast	Healthy
THBS2	SDC1	THBS2_SDC1	THBS	Breast	IDC
THBS2	SDC4	THBS2_SDC4	THBS	Breast	IDC
THBS2	CD36	THBS2_CD36	THBS	Breast	IDC
THBS2	CD47	THBS2_CD47	THBS	Breast	IDC
THBS2	SDC4	THBS2_SDC4	THBS	Breast	Precancer
THBS2	CD36	THBS2_CD36	THBS	Breast	Precancer
THBS2	CD47	THBS2_CD47	THBS	Breast	Precancer
THBS2	ITGA3_ITGB1	THBS2_ITGA3_ITGB1	THBS	Cervix	ADJ
THBS2	SDC1	THBS2_SDC1	THBS	Cervix	ADJ
THBS2	SDC4	THBS2_SDC4	THBS	Cervix	ADJ

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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

THBS2

SNV

Missense_Mutation

rs142358231

c.47C>T

p.Thr16Met

p.T16M

P35442

protein_coding

tolerated_low_confidence(0.26)

benign(0.05)

TCGA-3C-AALK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

docetaxel

THBS2

SNV

Missense_Mutation

c.2500C>A

p.His834Asn

p.H834N

P35442

protein_coding

tolerated(0.43)

benign(0.212)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

THBS2

SNV

Missense_Mutation

rs202062355

c.706N>A

p.Ala236Thr

p.A236T

P35442

protein_coding

tolerated_low_confidence(0.67)

benign(0.003)

TCGA-AC-A8OR-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

THBS2

SNV

Missense_Mutation

c.1378N>T

p.Arg460Cys

p.R460C

P35442

protein_coding

deleterious(0)

probably_damaging(0.992)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

THBS2

SNV

Missense_Mutation

c.2464N>A

p.Asp822Asn

p.D822N

P35442

protein_coding

tolerated(0.11)

possibly_damaging(0.722)

TCGA-BH-A0DX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

THBS2

SNV

Missense_Mutation

rs748278174

c.55G>A

p.Gly19Ser

p.G19S

P35442

protein_coding

tolerated_low_confidence(0.39)

benign(0.011)

TCGA-E2-A14N-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

THBS2

SNV

Missense_Mutation

rs756790082

c.790G>A

p.Glu264Lys

p.E264K

P35442

protein_coding

tolerated_low_confidence(0.42)

benign(0.157)

TCGA-LL-A73Z-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

THBS2

SNV

Missense_Mutation

novel

c.424G>A

p.Val142Ile

p.V142I

P35442

protein_coding

deleterious(0.01)

probably_damaging(0.99)

TCGA-LL-A73Z-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

THBS2

insertion

Frame_Shift_Ins

novel

c.2803_2804insCTCCCATGCAGCT

p.Asp935AlafsTer7

p.D935Afs*7

P35442

protein_coding

TCGA-A8-A093-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

THBS2

deletion

Frame_Shift_Del

novel

c.2497delN

p.Asp833IlefsTer32

p.D833Ifs*32

P35442

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

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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
7058	THBS2	DRUGGABLE GENOME		BEVACIZUMAB	BEVACIZUMAB	16365183
7058	THBS2	DRUGGABLE GENOME		ADRENOCORTICOTROPIC HORMONE		8698834

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