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: SLPI

Gene summary for SLPI

Gene summary.

Gene information	Species	Human
	Gene symbol	SLPI
	Gene ID	6590
	Gene name	secretory leukocyte peptidase inhibitor
	Gene Alias	ALK1
	Cytomap	20q13.12
	Gene Type	protein-coding
	GO ID	GO:0002237
	UniProtAcc	P03973

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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
6590	SLPI	GSM4909281	Human	Breast	IDC	5.55e-27	-8.78e-01	0.21
6590	SLPI	GSM4909282	Human	Breast	IDC	1.28e-35	7.90e-01	-0.0288
6590	SLPI	GSM4909285	Human	Breast	IDC	5.52e-34	6.82e-01	0.21
6590	SLPI	GSM4909286	Human	Breast	IDC	4.83e-25	-8.48e-01	0.1081
6590	SLPI	GSM4909290	Human	Breast	IDC	1.45e-11	-6.42e-01	0.2096
6590	SLPI	GSM4909291	Human	Breast	IDC	1.49e-27	-1.06e+00	0.1753
6590	SLPI	GSM4909293	Human	Breast	IDC	7.90e-39	-9.47e-01	0.1581
6590	SLPI	GSM4909294	Human	Breast	IDC	3.13e-27	-8.65e-01	0.2022
6590	SLPI	GSM4909296	Human	Breast	IDC	4.37e-04	-3.75e-01	0.1524
6590	SLPI	GSM4909297	Human	Breast	IDC	7.23e-32	-8.91e-01	0.1517
6590	SLPI	GSM4909298	Human	Breast	IDC	8.92e-25	-7.83e-01	0.1551
6590	SLPI	GSM4909300	Human	Breast	IDC	2.90e-12	7.54e-01	0.0334
6590	SLPI	GSM4909301	Human	Breast	IDC	1.26e-52	-1.07e+00	0.1577
6590	SLPI	GSM4909302	Human	Breast	IDC	2.95e-31	-9.29e-01	0.1545
6590	SLPI	GSM4909303	Human	Breast	IDC	6.61e-05	-7.62e-01	0.0438
6590	SLPI	GSM4909304	Human	Breast	IDC	1.41e-37	-9.72e-01	0.1636
6590	SLPI	GSM4909306	Human	Breast	IDC	1.84e-19	-7.32e-01	0.1564
6590	SLPI	GSM4909307	Human	Breast	IDC	2.03e-12	-4.22e-01	0.1569
6590	SLPI	GSM4909308	Human	Breast	IDC	1.04e-39	-1.07e+00	0.158
6590	SLPI	GSM4909311	Human	Breast	IDC	2.64e-24	-5.97e-01	0.1534

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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
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
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
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:00525479	Breast	Precancer	regulation of peptidase activity	71/1080	461/18723	2.72e-14	6.94e-12	71
GO:00525489	Breast	Precancer	regulation of endopeptidase activity	67/1080	432/18723	1.06e-13	2.36e-11	67
GO:00160329	Breast	Precancer	viral process	58/1080	415/18723	3.42e-10	3.16e-08	58
GO:00190589	Breast	Precancer	viral life cycle	47/1080	317/18723	2.42e-09	1.99e-07	47
GO:00458619	Breast	Precancer	negative regulation of proteolysis	50/1080	351/18723	2.99e-09	2.39e-07	50
GO:00513468	Breast	Precancer	negative regulation of hydrolase activity	50/1080	379/18723	3.85e-08	2.34e-06	50
GO:00104668	Breast	Precancer	negative regulation of peptidase activity	38/1080	262/18723	1.46e-07	7.82e-06	38
GO:00109519	Breast	Precancer	negative regulation of endopeptidase activity	37/1080	252/18723	1.55e-07	8.05e-06	37
GO:00507929	Breast	Precancer	regulation of viral process	27/1080	164/18723	7.59e-07	3.05e-05	27
GO:00510989	Breast	Precancer	regulation of binding	44/1080	363/18723	2.59e-06	8.65e-05	44
GO:00190799	Breast	Precancer	viral genome replication	22/1080	131/18723	5.63e-06	1.66e-04	22
GO:00022378	Breast	Precancer	response to molecule of bacterial origin	43/1080	363/18723	6.05e-06	1.72e-04	43
GO:00324968	Breast	Precancer	response to lipopolysaccharide	41/1080	343/18723	7.94e-06	2.17e-04	41
GO:19039009	Breast	Precancer	regulation of viral life cycle	23/1080	148/18723	1.31e-05	3.30e-04	23
GO:00197307	Breast	Precancer	antimicrobial humoral response	19/1080	122/18723	7.02e-05	1.40e-03	19
GO:00450697	Breast	Precancer	regulation of viral genome replication	13/1080	85/18723	1.12e-03	1.23e-02	13
GO:00511008	Breast	Precancer	negative regulation of binding	19/1080	162/18723	2.56e-03	2.32e-02	19
GO:00485255	Breast	Precancer	negative regulation of viral process	12/1080	92/18723	6.51e-03	4.51e-02	12
GO:005254714	Breast	IDC	regulation of peptidase activity	96/1434	461/18723	7.58e-20	6.15e-17	96
GO:005254814	Breast	IDC	regulation of endopeptidase activity	88/1434	432/18723	1.20e-17	4.85e-15	88

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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

SLPI

SNV

Missense_Mutation

novel

c.11N>A

p.Ser4Asn

p.S4N

P03973

protein_coding

tolerated(0.21)

benign(0.026)

TCGA-AP-A1DK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

SLPI

SNV

Missense_Mutation

c.238A>G

p.Asn80Asp

p.N80D

P03973

protein_coding

tolerated(0.29)

benign(0.015)

TCGA-B5-A0JY-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

SLPI

SNV

Missense_Mutation

novel

c.352T>C

p.Cys118Arg

p.C118R

P03973

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-B5-A3FA-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

SLPI

SNV

Missense_Mutation

c.238N>C

p.Asn80His

p.N80H

P03973

protein_coding

deleterious(0.03)

benign(0.188)

TCGA-BS-A0UV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

SLPI

SNV

Missense_Mutation

novel

c.141G>T

p.Lys47Asn

p.K47N

P03973

protein_coding

deleterious(0)

benign(0.001)

TCGA-EO-A3AY-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

SLPI

SNV

Missense_Mutation

novel

c.185G>T

p.Arg62Ile

p.R62I

P03973

protein_coding

tolerated(0.11)

benign(0.062)

TCGA-EO-A3B0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

SLPI

insertion

Frame_Shift_Ins

rs745834619

c.306_307insC

p.Asn103GlnfsTer4

p.N103Qfs*4

P03973

protein_coding

TCGA-DF-A2KY-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatin

SLPI

SNV

Missense_Mutation

novel

c.196N>A

p.Asp66Asn

p.D66N

P03973

protein_coding

tolerated(0.09)

possibly_damaging(0.628)

TCGA-XR-A8TD-01

Liver

liver hepatocellular carcinoma

Female

<65

III/IV

Unknown

SLPI

SNV

Missense_Mutation

c.77N>G

p.Ser26Cys

p.S26C

P03973

protein_coding

deleterious(0.01)

benign(0.24)

TCGA-49-6743-01

Lung

lung adenocarcinoma

Female

>=65

III/IV

Chemotherapy

cisplatin

SLPI

SNV

Missense_Mutation

novel

c.101T>A

p.Val34Asp

p.V34D

P03973

protein_coding

tolerated(0.21)

possibly_damaging(0.472)

TCGA-52-7810-01

Lung

lung squamous cell carcinoma

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
6590	SLPI	ENZYME, DRUGGABLE GENOME, PROTEASE INHIBITOR		HEPARIN	HEPARIN	8615699,9593692
6590	SLPI	ENZYME, DRUGGABLE GENOME, PROTEASE INHIBITOR		CYTOKINES		11385113
6590	SLPI	ENZYME, DRUGGABLE GENOME, PROTEASE INHIBITOR		HGF		10970828
6590	SLPI	ENZYME, DRUGGABLE GENOME, PROTEASE INHIBITOR		TNF-ALPHA		12668158,17114478

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