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: SERPINB1

Gene summary for SERPINB1

Gene summary.

Gene information	Species	Human
	Gene symbol	SERPINB1
	Gene ID	1992
	Gene name	serpin family B member 1
	Gene Alias	EI
	Cytomap	6p25.2
	Gene Type	protein-coding
	GO ID	GO:0001816
	UniProtAcc	P30740

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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
1992	SERPINB1	CA_HPV_1	Human	Cervix	CC	1.43e-06	-1.14e-01	0.0264
1992	SERPINB1	CCI_2	Human	Cervix	CC	3.42e-02	-5.86e-01	0.5249
1992	SERPINB1	CCII_1	Human	Cervix	CC	3.37e-13	-7.82e-01	0.3249
1992	SERPINB1	Tumor	Human	Cervix	CC	4.31e-04	3.27e-01	0.1241
1992	SERPINB1	sample3	Human	Cervix	CC	8.64e-14	4.48e-01	0.1387
1992	SERPINB1	L1	Human	Cervix	CC	6.25e-04	-3.82e-01	0.0802
1992	SERPINB1	T3	Human	Cervix	CC	5.70e-12	4.74e-01	0.1389
1992	SERPINB1	HTA11_3410_2000001011	Human	Colorectum	AD	3.49e-10	5.00e-01	0.0155
1992	SERPINB1	HTA11_2487_2000001011	Human	Colorectum	SER	1.68e-10	8.68e-01	-0.1808
1992	SERPINB1	HTA11_1938_2000001011	Human	Colorectum	AD	3.29e-19	1.14e+00	-0.0811
1992	SERPINB1	HTA11_78_2000001011	Human	Colorectum	AD	3.82e-16	9.17e-01	-0.1088
1992	SERPINB1	HTA11_347_2000001011	Human	Colorectum	AD	1.77e-26	8.17e-01	-0.1954
1992	SERPINB1	HTA11_411_2000001011	Human	Colorectum	SER	1.68e-08	1.20e+00	-0.2602
1992	SERPINB1	HTA11_83_2000001011	Human	Colorectum	SER	1.46e-05	6.33e-01	-0.1526
1992	SERPINB1	HTA11_696_2000001011	Human	Colorectum	AD	1.24e-17	6.77e-01	-0.1464
1992	SERPINB1	HTA11_866_2000001011	Human	Colorectum	AD	1.60e-03	3.20e-01	-0.1001
1992	SERPINB1	HTA11_1391_2000001011	Human	Colorectum	AD	1.32e-20	1.33e+00	-0.059
1992	SERPINB1	HTA11_7862_2000001011	Human	Colorectum	AD	3.42e-02	4.17e-01	-0.0179
1992	SERPINB1	HTA11_866_3004761011	Human	Colorectum	AD	6.57e-05	5.14e-01	0.096
1992	SERPINB1	HTA11_4255_2000001011	Human	Colorectum	SER	2.63e-07	9.34e-01	0.0446

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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
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
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:005254710	Cervix	CC	regulation of peptidase activity	112/2311	461/18723	6.70e-13	3.08e-10	112
GO:005254810	Cervix	CC	regulation of endopeptidase activity	103/2311	432/18723	1.89e-11	5.14e-09	103
GO:00506737	Cervix	CC	epithelial cell proliferation	98/2311	437/18723	2.01e-09	2.15e-07	98
GO:004586110	Cervix	CC	negative regulation of proteolysis	80/2311	351/18723	2.88e-08	1.98e-06	80
GO:00513469	Cervix	CC	negative regulation of hydrolase activity	81/2311	379/18723	4.27e-07	1.67e-05	81
GO:00104669	Cervix	CC	negative regulation of peptidase activity	60/2311	262/18723	1.27e-06	4.34e-05	60
GO:001095110	Cervix	CC	negative regulation of endopeptidase activity	56/2311	252/18723	7.43e-06	1.74e-04	56
GO:00093149	Cervix	CC	response to radiation	86/2311	456/18723	3.50e-05	5.63e-04	86
GO:00094112	Cervix	CC	response to UV	33/2311	149/18723	5.51e-04	5.29e-03	33
GO:19040194	Cervix	CC	epithelial cell apoptotic process	27/2311	121/18723	1.49e-03	1.16e-02	27
GO:00094163	Cervix	CC	response to light stimulus	54/2311	320/18723	1.03e-02	4.97e-02	54
GO:0052547	Colorectum	AD	regulation of peptidase activity	137/3918	461/18723	4.12e-06	1.12e-04	137
GO:0045861	Colorectum	AD	negative regulation of proteolysis	106/3918	351/18723	2.33e-05	4.57e-04	106
GO:0052548	Colorectum	AD	regulation of endopeptidase activity	124/3918	432/18723	6.58e-05	1.07e-03	124
GO:0050673	Colorectum	AD	epithelial cell proliferation	119/3918	437/18723	8.75e-04	8.51e-03	119
GO:00525471	Colorectum	SER	regulation of peptidase activity	114/2897	461/18723	1.18e-07	7.17e-06	114
GO:00458611	Colorectum	SER	negative regulation of proteolysis	88/2897	351/18723	1.74e-06	7.50e-05	88
GO:00525481	Colorectum	SER	regulation of endopeptidase activity	103/2897	432/18723	2.86e-06	1.16e-04	103
GO:0051346	Colorectum	SER	negative regulation of hydrolase activity	82/2897	379/18723	8.19e-04	1.01e-02	82
GO:0010466	Colorectum	SER	negative regulation of peptidase activity	57/2897	262/18723	4.15e-03	3.38e-02	57

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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

SERPINB1

SNV

Missense_Mutation

rs757989972

c.1094N>G

p.Asn365Ser

p.N365S

P30740

protein_coding

tolerated(0.07)

benign(0.355)

TCGA-A1-A0SH-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

SERPINB1

SNV

Missense_Mutation

c.119N>G

p.Ala40Gly

p.A40G

P30740

protein_coding

deleterious(0.05)

benign(0.068)

TCGA-C8-A27B-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

SERPINB1

SNV

Missense_Mutation

c.105N>G

p.Ile35Met

p.I35M

P30740

protein_coding

deleterious(0.02)

possibly_damaging(0.597)

TCGA-D8-A1XQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SERPINB1

insertion

In_Frame_Ins

novel

c.668_669insATTGTTTTA

p.Gly223_Glu224insLeuPheTyr

p.G223_E224insLFY

P30740

protein_coding

TCGA-A8-A0A4-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

SERPINB1

deletion

Frame_Shift_Del

c.1021delN

p.Ala341GlnfsTer6

p.A341Qfs*6

P30740

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

SERPINB1

SNV

Missense_Mutation

rs752211279

c.869G>A

p.Arg290His

p.R290H

P30740

protein_coding

tolerated(0.2)

benign(0.007)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SERPINB1

SNV

Missense_Mutation

c.703N>A

p.Asp235Asn

p.D235N

P30740

protein_coding

tolerated(0.11)

benign(0.04)

TCGA-C5-A7X3-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

SERPINB1

SNV

Missense_Mutation

c.1063N>A

p.Asp355Asn

p.D355N

P30740

protein_coding

tolerated(0.08)

possibly_damaging(0.503)

TCGA-F4-6704-01

Colorectum

colon adenocarcinoma

Male

<65

III/IV

Unknown

SERPINB1

deletion

Frame_Shift_Del

c.608_609delNN

p.Lys203IlefsTer10

p.K203Ifs*10

P30740

protein_coding

TCGA-D5-6530-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

SERPINB1

SNV

Missense_Mutation

rs775777099

c.34N>A

p.Ala12Thr

p.A12T

P30740

protein_coding

tolerated(0.13)

benign(0.293)

TCGA-A5-A0G1-01

Endometrium

uterine corpus endometrioid 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

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