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: TMPRSS2

Gene summary for TMPRSS2

Gene summary.

Gene information	Species	Human
	Gene symbol	TMPRSS2
	Gene ID	7113
	Gene name	transmembrane serine protease 2
	Gene Alias	PRSS10
	Cytomap	21q22.3
	Gene Type	protein-coding
	GO ID	GO:0006508
	UniProtAcc	O15393

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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
7113	TMPRSS2	HTA11_2487_2000001011	Human	Colorectum	SER	9.51e-03	6.36e-01	-0.1808
7113	TMPRSS2	HTA11_347_2000001011	Human	Colorectum	AD	2.16e-11	7.38e-01	-0.1954
7113	TMPRSS2	HTA11_411_2000001011	Human	Colorectum	SER	3.18e-07	1.53e+00	-0.2602
7113	TMPRSS2	HTA11_2112_2000001011	Human	Colorectum	SER	8.42e-10	1.24e+00	-0.2196
7113	TMPRSS2	HTA11_696_2000001011	Human	Colorectum	AD	5.89e-04	6.01e-01	-0.1464
7113	TMPRSS2	HTA11_5212_2000001011	Human	Colorectum	AD	2.55e-04	8.28e-01	-0.2061
7113	TMPRSS2	HTA11_10711_2000001011	Human	Colorectum	AD	1.35e-03	-3.06e-01	0.0338
7113	TMPRSS2	F007	Human	Colorectum	FAP	8.73e-08	-4.67e-01	0.1176
7113	TMPRSS2	A002-C-010	Human	Colorectum	FAP	1.17e-02	-2.86e-01	0.242
7113	TMPRSS2	A001-C-207	Human	Colorectum	FAP	5.98e-07	-3.07e-01	0.1278
7113	TMPRSS2	A015-C-203	Human	Colorectum	FAP	1.20e-29	-4.32e-01	-0.1294
7113	TMPRSS2	A015-C-204	Human	Colorectum	FAP	3.45e-10	-3.56e-01	-0.0228
7113	TMPRSS2	A014-C-040	Human	Colorectum	FAP	1.10e-06	-5.36e-01	-0.1184
7113	TMPRSS2	A002-C-201	Human	Colorectum	FAP	5.78e-25	-5.43e-01	0.0324
7113	TMPRSS2	A002-C-203	Human	Colorectum	FAP	3.89e-04	-2.51e-01	0.2786
7113	TMPRSS2	A001-C-119	Human	Colorectum	FAP	1.37e-07	-1.95e-01	-0.1557
7113	TMPRSS2	A001-C-108	Human	Colorectum	FAP	3.08e-14	-3.81e-01	-0.0272
7113	TMPRSS2	A002-C-205	Human	Colorectum	FAP	3.87e-32	-5.57e-01	-0.1236
7113	TMPRSS2	A001-C-104	Human	Colorectum	FAP	3.33e-03	-2.58e-01	0.0184
7113	TMPRSS2	A015-C-005	Human	Colorectum	FAP	2.44e-02	-2.30e-02	-0.0336

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
Colorectum (GSE201348)		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
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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:0016032	Colorectum	AD	viral process	168/3918	415/18723	4.67e-20	3.66e-17	168
GO:0019058	Colorectum	AD	viral life cycle	119/3918	317/18723	6.18e-12	8.23e-10	119
GO:0044403	Colorectum	AD	biological process involved in symbiotic interaction	99/3918	290/18723	1.02e-07	4.93e-06	99
GO:0051701	Colorectum	AD	biological process involved in interaction with host	73/3918	203/18723	5.08e-07	1.88e-05	73
GO:0048524	Colorectum	AD	positive regulation of viral process	31/3918	65/18723	1.33e-06	4.23e-05	31
GO:0052126	Colorectum	AD	movement in host environment	63/3918	175/18723	2.85e-06	8.11e-05	63
GO:0050792	Colorectum	AD	regulation of viral process	59/3918	164/18723	5.95e-06	1.52e-04	59
GO:0046718	Colorectum	AD	viral entry into host cell	51/3918	144/18723	3.99e-05	7.16e-04	51
GO:1903900	Colorectum	AD	regulation of viral life cycle	51/3918	148/18723	9.01e-05	1.38e-03	51
GO:0044409	Colorectum	AD	entry into host	51/3918	151/18723	1.60e-04	2.21e-03	51
GO:0051604	Colorectum	AD	protein maturation	85/3918	294/18723	6.73e-04	6.91e-03	85
GO:1903902	Colorectum	AD	positive regulation of viral life cycle	14/3918	29/18723	9.40e-04	8.92e-03	14
GO:0016485	Colorectum	AD	protein processing	63/3918	225/18723	6.77e-03	4.19e-02	63
GO:00160321	Colorectum	SER	viral process	118/2897	415/18723	8.36e-12	1.65e-09	118
GO:00190581	Colorectum	SER	viral life cycle	87/2897	317/18723	2.82e-08	1.94e-06	87
GO:00517011	Colorectum	SER	biological process involved in interaction with host	55/2897	203/18723	1.42e-05	4.38e-04	55
GO:00516041	Colorectum	SER	protein maturation	73/2897	294/18723	1.82e-05	5.38e-04	73
GO:00444031	Colorectum	SER	biological process involved in symbiotic interaction	72/2897	290/18723	2.08e-05	6.02e-04	72
GO:00521261	Colorectum	SER	movement in host environment	47/2897	175/18723	7.30e-05	1.64e-03	47
GO:00507921	Colorectum	SER	regulation of viral process	43/2897	164/18723	2.57e-04	4.31e-03	43

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05171	Colorectum	AD	Coronavirus disease - COVID-19	113/2092	232/8465	9.90e-16	2.55e-14	1.63e-14	113
hsa051711	Colorectum	AD	Coronavirus disease - COVID-19	113/2092	232/8465	9.90e-16	2.55e-14	1.63e-14	113
hsa051712	Colorectum	SER	Coronavirus disease - COVID-19	98/1580	232/8465	3.33e-17	8.50e-16	6.17e-16	98
hsa051713	Colorectum	SER	Coronavirus disease - COVID-19	98/1580	232/8465	3.33e-17	8.50e-16	6.17e-16	98
hsa051718	Colorectum	FAP	Coronavirus disease - COVID-19	78/1404	232/8465	9.94e-11	1.11e-08	6.73e-09	78
hsa052152	Colorectum	FAP	Prostate cancer	28/1404	97/8465	1.67e-03	8.57e-03	5.21e-03	28
hsa05202	Colorectum	FAP	Transcriptional misregulation in cancer	45/1404	193/8465	9.19e-03	3.33e-02	2.03e-02	45
hsa051719	Colorectum	FAP	Coronavirus disease - COVID-19	78/1404	232/8465	9.94e-11	1.11e-08	6.73e-09	78
hsa052153	Colorectum	FAP	Prostate cancer	28/1404	97/8465	1.67e-03	8.57e-03	5.21e-03	28
hsa052021	Colorectum	FAP	Transcriptional misregulation in cancer	45/1404	193/8465	9.19e-03	3.33e-02	2.03e-02	45
hsa0517110	Colorectum	CRC	Coronavirus disease - COVID-19	74/1091	232/8465	1.66e-14	2.78e-12	1.88e-12	74
hsa052154	Colorectum	CRC	Prostate cancer	21/1091	97/8465	1.08e-02	4.74e-02	3.21e-02	21
hsa0517111	Colorectum	CRC	Coronavirus disease - COVID-19	74/1091	232/8465	1.66e-14	2.78e-12	1.88e-12	74
hsa052155	Colorectum	CRC	Prostate cancer	21/1091	97/8465	1.08e-02	4.74e-02	3.21e-02	21
hsa0516425	Esophagus	ESCC	Influenza A	122/4205	171/8465	5.01e-09	4.79e-08	2.45e-08	122
hsa05171211	Esophagus	ESCC	Coronavirus disease - COVID-19	156/4205	232/8465	3.18e-08	2.68e-07	1.37e-07	156
hsa0521516	Esophagus	ESCC	Prostate cancer	72/4205	97/8465	6.12e-07	4.10e-06	2.10e-06	72
hsa052028	Esophagus	ESCC	Transcriptional misregulation in cancer	116/4205	193/8465	2.08e-03	5.95e-03	3.05e-03	116
hsa0516435	Esophagus	ESCC	Influenza A	122/4205	171/8465	5.01e-09	4.79e-08	2.45e-08	122
hsa05171310	Esophagus	ESCC	Coronavirus disease - COVID-19	156/4205	232/8465	3.18e-08	2.68e-07	1.37e-07	156

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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

TMPRSS2

insertion

Frame_Shift_Ins

novel

c.699_700insGCACCTGTAGTCACTGAGAACCCGGGGGGTGTGCC

p.Ser234AlafsTer16

p.S234Afs*16

O15393

protein_coding

TCGA-A8-A06O-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

letrozole

TMPRSS2

insertion

Frame_Shift_Ins

novel

c.1563_1564insACAA

p.Tyr522ThrfsTer38

p.Y522Tfs*38

O15393

protein_coding

TCGA-AN-A0FN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TMPRSS2

insertion

Frame_Shift_Ins

novel

c.1561_1562insATCACTCCCTGCTTCTATCTTCAGTATCTCCTCA

p.Ile521AsnfsTer49

p.I521Nfs*49

O15393

protein_coding

TCGA-AN-A0FN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TMPRSS2

SNV

Missense_Mutation

rs185312677

c.1306N>A

p.Ala436Thr

p.A436T

O15393

protein_coding

tolerated(0.35)

possibly_damaging(0.844)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TMPRSS2

SNV

Missense_Mutation

rs375223866

c.91N>A

p.Asp31Asn

p.D31N

O15393

protein_coding

tolerated_low_confidence(0.08)

possibly_damaging(0.801)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TMPRSS2

SNV

Missense_Mutation

novel

c.864N>A

p.Ser288Arg

p.S288R

O15393

protein_coding

tolerated(0.49)

benign(0.003)

TCGA-EA-A410-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

TMPRSS2

SNV

Missense_Mutation

novel

c.1024N>T

p.Pro342Ser

p.P342S

O15393

protein_coding

deleterious(0.01)

possibly_damaging(0.864)

TCGA-VS-A94Y-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TMPRSS2

SNV

Missense_Mutation

rs757262240

c.655C>T

p.Arg219Trp

p.R219W

O15393

protein_coding

deleterious(0.03)

benign(0.109)

TCGA-A6-5660-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Ancillary

leucovorin

TMPRSS2

SNV

Missense_Mutation

c.1039G>A

p.Ala347Thr

p.A347T

O15393

protein_coding

deleterious(0.01)

benign(0.193)

TCGA-A6-A565-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Unspecific

5FU

TMPRSS2

SNV

Missense_Mutation

rs757634613

c.955G>A

p.Gly319Arg

p.G319R

O15393

protein_coding

deleterious(0.01)

possibly_damaging(0.855)

TCGA-AA-3514-01

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
7113	TMPRSS2	CLINICALLY ACTIONABLE, PROTEASE, DRUGGABLE GENOME, ENZYME	inhibitor	178103048	CAMOSTAT
7113	TMPRSS2	CLINICALLY ACTIONABLE, PROTEASE, DRUGGABLE GENOME, ENZYME	inhibitor	252166870
7113	TMPRSS2	CLINICALLY ACTIONABLE, PROTEASE, DRUGGABLE GENOME, ENZYME	inhibitor	405067326
7113	TMPRSS2	CLINICALLY ACTIONABLE, PROTEASE, DRUGGABLE GENOME, ENZYME	inhibitor	178101079	NAFAMOSTAT

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