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: TSPAN1

Gene summary for TSPAN1

Gene summary.

Gene information	Species	Human
	Gene symbol	TSPAN1
	Gene ID	10103
	Gene name	tetraspanin 1
	Gene Alias	NET1
	Cytomap	1p34.1
	Gene Type	protein-coding
	GO ID	GO:0008150
	UniProtAcc	O60635

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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
10103	TSPAN1	CA_HPV_1	Human	Cervix	CC	8.77e-10	-2.46e-01	0.0264
10103	TSPAN1	HSIL_HPV_1	Human	Cervix	HSIL_HPV	6.04e-03	-1.44e-01	0.0116
10103	TSPAN1	HSIL_HPV_2	Human	Cervix	HSIL_HPV	6.76e-04	3.27e-01	0.0208
10103	TSPAN1	N_HPV_1	Human	Cervix	N_HPV	2.98e-03	-1.97e-01	0.0079
10103	TSPAN1	CCI_3	Human	Cervix	CC	1.69e-02	-2.49e-01	0.516
10103	TSPAN1	Tumor	Human	Cervix	CC	2.51e-04	3.32e-01	0.1241
10103	TSPAN1	sample1	Human	Cervix	CC	3.27e-02	4.38e-01	0.0959
10103	TSPAN1	sample3	Human	Cervix	CC	1.26e-15	4.65e-01	0.1387
10103	TSPAN1	H2	Human	Cervix	HSIL_HPV	1.69e-03	3.19e-01	0.0632
10103	TSPAN1	T2	Human	Cervix	CC	2.68e-08	7.32e-01	0.0709
10103	TSPAN1	T3	Human	Cervix	CC	4.71e-17	4.65e-01	0.1389
10103	TSPAN1	HTA11_3410_2000001011	Human	Colorectum	AD	3.27e-03	-1.13e-01	0.0155
10103	TSPAN1	HTA11_2487_2000001011	Human	Colorectum	SER	5.10e-38	2.58e+00	-0.1808
10103	TSPAN1	HTA11_1938_2000001011	Human	Colorectum	AD	8.34e-38	1.74e+00	-0.0811
10103	TSPAN1	HTA11_78_2000001011	Human	Colorectum	AD	3.11e-21	1.10e+00	-0.1088
10103	TSPAN1	HTA11_347_2000001011	Human	Colorectum	AD	1.98e-51	1.90e+00	-0.1954
10103	TSPAN1	HTA11_411_2000001011	Human	Colorectum	SER	7.02e-18	3.79e+00	-0.2602
10103	TSPAN1	HTA11_2112_2000001011	Human	Colorectum	SER	3.24e-24	3.66e+00	-0.2196
10103	TSPAN1	HTA11_3361_2000001011	Human	Colorectum	AD	2.18e-25	1.39e+00	-0.1207
10103	TSPAN1	HTA11_83_2000001011	Human	Colorectum	SER	6.38e-25	1.78e+00	-0.1526

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
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:00109596	Breast	Precancer	regulation of metal ion transport	37/1080	406/18723	4.07e-03	3.22e-02	37
GO:001095913	Breast	IDC	regulation of metal ion transport	52/1434	406/18723	1.76e-04	2.97e-03	52
GO:0051924	Breast	IDC	regulation of calcium ion transport	32/1434	255/18723	3.94e-03	3.22e-02	32
GO:001095921	Breast	DCIS	regulation of metal ion transport	50/1390	406/18723	2.86e-04	4.22e-03	50
GO:003164710	Cervix	CC	regulation of protein stability	63/2311	298/18723	1.14e-05	2.45e-04	63
GO:005082110	Cervix	CC	protein stabilization	43/2311	191/18723	5.90e-05	8.54e-04	43
GO:003164715	Cervix	HSIL_HPV	regulation of protein stability	31/737	298/18723	8.69e-07	4.19e-05	31
GO:005082115	Cervix	HSIL_HPV	protein stabilization	21/737	191/18723	2.17e-05	6.58e-04	21
GO:005082125	Cervix	N_HPV	protein stabilization	14/534	191/18723	1.20e-03	1.34e-02	14
GO:003164725	Cervix	N_HPV	regulation of protein stability	17/534	298/18723	5.47e-03	3.90e-02	17
GO:0072659	Colorectum	AD	protein localization to plasma membrane	122/3918	284/18723	2.86e-17	1.49e-14	122
GO:1990778	Colorectum	AD	protein localization to cell periphery	129/3918	333/18723	5.51e-14	1.15e-11	129
GO:0031647	Colorectum	AD	regulation of protein stability	108/3918	298/18723	6.33e-10	5.08e-08	108
GO:0050821	Colorectum	AD	protein stabilization	73/3918	191/18723	3.02e-08	1.64e-06	73
GO:0051604	Colorectum	AD	protein maturation	85/3918	294/18723	6.73e-04	6.91e-03	85
GO:0007219	Colorectum	AD	Notch signaling pathway	50/3918	172/18723	6.92e-03	4.26e-02	50
GO:00726591	Colorectum	SER	protein localization to plasma membrane	92/2897	284/18723	6.36e-13	1.86e-10	92
GO:19907781	Colorectum	SER	protein localization to cell periphery	98/2897	333/18723	6.09e-11	9.57e-09	98
GO:00316471	Colorectum	SER	regulation of protein stability	86/2897	298/18723	2.56e-09	2.42e-07	86
GO:00508211	Colorectum	SER	protein stabilization	58/2897	191/18723	1.46e-07	8.59e-06	58

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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

TSPAN1

SNV

Missense_Mutation

novel

c.307G>A

p.Ala103Thr

p.A103T

O60635

protein_coding

tolerated(0.09)

possibly_damaging(0.907)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TSPAN1

SNV

Missense_Mutation

c.678N>T

p.Glu226Asp

p.E226D

O60635

protein_coding

deleterious(0)

probably_damaging(0.992)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TSPAN1

SNV

Missense_Mutation

c.427N>G

p.Thr143Ala

p.T143A

O60635

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

TSPAN1

SNV

Missense_Mutation

c.378C>G

p.Ile126Met

p.I126M

O60635

protein_coding

deleterious(0.01)

probably_damaging(0.973)

TCGA-B6-A0RH-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TSPAN1

insertion

Frame_Shift_Ins

novel

c.397_398insCT

p.Gln133ProfsTer13

p.Q133Pfs*13

O60635

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TSPAN1

insertion

In_Frame_Ins

novel

c.398_399insGGCTCAGGCTTCTGTCTCACTTTTCCGGGGGGG

p.Gln133_Glu134insAlaGlnAlaSerValSerLeuPheArgGlyGly

p.Q133_E134insAQASVSLFRGG

O60635

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TSPAN1

SNV

Missense_Mutation

c.356C>T

p.Thr119Met

p.T119M

O60635

protein_coding

tolerated(0.09)

benign(0.131)

TCGA-AZ-4615-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Chemotherapy

xeloda

TSPAN1

SNV

Missense_Mutation

novel

c.595N>T

p.Gly199Cys

p.G199C

O60635

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

TSPAN1

SNV

Missense_Mutation

novel

c.227A>G

p.Tyr76Cys

p.Y76C

O60635

protein_coding

tolerated(0.75)

benign(0.018)

TCGA-AJ-A3BH-01

Endometrium

uterine corpus endometrioid carcinoma

Female

Unknown

I/II

Unknown

TSPAN1

SNV

Missense_Mutation

c.436N>T

p.Gly146Trp

p.G146W

O60635

protein_coding

deleterious(0.01)

possibly_damaging(0.886)

TCGA-AP-A0LM-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

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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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