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: PCNP

Gene summary for PCNP

Gene summary.

Gene information	Species	Human
	Gene symbol	PCNP
	Gene ID	57092
	Gene name	PEST proteolytic signal containing nuclear protein
	Gene Alias	PCNP
	Cytomap	3q12.3
	Gene Type	protein-coding
	GO ID	GO:0006464
	UniProtAcc	Q8WW12

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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
57092	PCNP	GSM4909280	Human	Breast	Precancer	4.55e-02	-2.61e-01	0.0305
57092	PCNP	GSM4909286	Human	Breast	IDC	3.64e-02	-3.26e-02	0.1081
57092	PCNP	GSM4909287	Human	Breast	IDC	9.77e-03	-3.29e-01	0.2057
57092	PCNP	GSM4909288	Human	Breast	IDC	5.68e-04	-2.24e-01	0.0988
57092	PCNP	GSM4909294	Human	Breast	IDC	3.15e-06	-2.61e-01	0.2022
57092	PCNP	GSM4909296	Human	Breast	IDC	1.14e-17	-4.17e-01	0.1524
57092	PCNP	GSM4909297	Human	Breast	IDC	8.99e-20	-1.32e-01	0.1517
57092	PCNP	GSM4909301	Human	Breast	IDC	5.97e-07	-3.20e-01	0.1577
57092	PCNP	GSM4909302	Human	Breast	IDC	4.41e-05	-3.21e-01	0.1545
57092	PCNP	GSM4909307	Human	Breast	IDC	4.66e-10	-3.40e-01	0.1569
57092	PCNP	GSM4909309	Human	Breast	IDC	9.42e-09	-3.66e-01	0.0483
57092	PCNP	GSM4909311	Human	Breast	IDC	1.87e-36	-4.96e-01	0.1534
57092	PCNP	GSM4909312	Human	Breast	IDC	7.44e-14	-2.21e-01	0.1552
57092	PCNP	GSM4909313	Human	Breast	IDC	3.86e-02	-1.78e-01	0.0391
57092	PCNP	GSM4909316	Human	Breast	IDC	4.79e-07	9.05e-02	0.21
57092	PCNP	GSM4909319	Human	Breast	IDC	1.04e-40	-5.36e-01	0.1563
57092	PCNP	GSM4909320	Human	Breast	IDC	3.38e-07	-5.22e-01	0.1575
57092	PCNP	GSM4909321	Human	Breast	IDC	3.72e-21	-3.45e-01	0.1559
57092	PCNP	brca2	Human	Breast	Precancer	2.65e-03	2.58e-01	-0.024
57092	PCNP	brca3	Human	Breast	Precancer	8.34e-06	2.91e-01	-0.0263

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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
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
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:00104989	Breast	Precancer	proteasomal protein catabolic process	58/1080	490/18723	1.54e-07	8.05e-06	58
GO:00431619	Breast	Precancer	proteasome-mediated ubiquitin-dependent protein catabolic process	42/1080	412/18723	2.49e-04	3.72e-03	42
GO:001049814	Breast	IDC	proteasomal protein catabolic process	75/1434	490/18723	5.59e-09	4.41e-07	75
GO:004316114	Breast	IDC	proteasome-mediated ubiquitin-dependent protein catabolic process	57/1434	412/18723	9.55e-06	2.68e-04	57
GO:001049824	Breast	DCIS	proteasomal protein catabolic process	75/1390	490/18723	1.44e-09	1.40e-07	75
GO:004316124	Breast	DCIS	proteasome-mediated ubiquitin-dependent protein catabolic process	57/1390	412/18723	3.76e-06	1.16e-04	57
GO:0010498	Colorectum	AD	proteasomal protein catabolic process	174/3918	490/18723	3.18e-14	7.66e-12	174
GO:0043161	Colorectum	AD	proteasome-mediated ubiquitin-dependent protein catabolic process	141/3918	412/18723	1.77e-10	1.68e-08	141
GO:00104981	Colorectum	SER	proteasomal protein catabolic process	132/2897	490/18723	3.08e-11	5.55e-09	132
GO:00431611	Colorectum	SER	proteasome-mediated ubiquitin-dependent protein catabolic process	105/2897	412/18723	7.48e-08	4.70e-06	105
GO:00104982	Colorectum	MSS	proteasomal protein catabolic process	157/3467	490/18723	2.39e-13	5.25e-11	157
GO:00431612	Colorectum	MSS	proteasome-mediated ubiquitin-dependent protein catabolic process	127/3467	412/18723	7.70e-10	6.32e-08	127
GO:00104983	Colorectum	MSI-H	proteasomal protein catabolic process	71/1319	490/18723	4.67e-09	6.03e-07	71
GO:00431613	Colorectum	MSI-H	proteasome-mediated ubiquitin-dependent protein catabolic process	53/1319	412/18723	1.51e-05	6.62e-04	53
GO:00431614	Colorectum	FAP	proteasome-mediated ubiquitin-dependent protein catabolic process	98/2622	412/18723	5.41e-08	4.20e-06	98
GO:00104984	Colorectum	FAP	proteasomal protein catabolic process	110/2622	490/18723	2.12e-07	1.26e-05	110
GO:001049816	Endometrium	AEH	proteasomal protein catabolic process	108/2100	490/18723	2.73e-12	4.67e-10	108
GO:004316116	Endometrium	AEH	proteasome-mediated ubiquitin-dependent protein catabolic process	88/2100	412/18723	1.54e-09	1.36e-07	88
GO:001049817	Endometrium	EEC	proteasomal protein catabolic process	112/2168	490/18723	6.99e-13	1.40e-10	112
GO:004316117	Endometrium	EEC	proteasome-mediated ubiquitin-dependent protein catabolic process	92/2168	412/18723	3.01e-10	3.23e-08	92

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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

PCNP

SNV

Missense_Mutation

c.529N>C

p.Asp177His

p.D177H

Q8WW12

protein_coding

deleterious_low_confidence(0)

benign(0.22)

TCGA-C5-A1BM-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

PCNP

SNV

Missense_Mutation

c.428C>T

p.Ala143Val

p.A143V

Q8WW12

protein_coding

deleterious(0)

probably_damaging(0.986)

TCGA-G4-6302-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

PCNP

SNV

Missense_Mutation

c.534N>G

p.Asn178Lys

p.N178K

Q8WW12

protein_coding

deleterious_low_confidence(0)

benign(0.017)

TCGA-AG-A002-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

PCNP

SNV

Missense_Mutation

novel

c.220N>A

p.Ala74Thr

p.A74T

Q8WW12

protein_coding

deleterious(0.01)

benign(0.088)

TCGA-AP-A059-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

PCNP

SNV

Missense_Mutation

c.259N>G

p.Ser87Ala

p.S87A

Q8WW12

protein_coding

deleterious(0.04)

probably_damaging(0.98)

TCGA-B5-A11H-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Hormone Therapy

megace

PCNP

SNV

Missense_Mutation

novel

c.283N>A

p.Pro95Thr

p.P95T

Q8WW12

protein_coding

tolerated(0.12)

probably_damaging(0.976)

TCGA-B5-A1MR-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Unknown

PCNP

SNV

Missense_Mutation

c.529G>T

p.Asp177Tyr

p.D177Y

Q8WW12

protein_coding

deleterious_low_confidence(0)

benign(0.001)

TCGA-B5-A1MX-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Hormone Therapy

megace

PCNP

insertion

Frame_Shift_Ins

novel

c.123_124insG

p.Glu43GlyfsTer8

p.E43Gfs*8

Q8WW12

protein_coding

TCGA-DF-A2KY-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatin

PCNP

SNV

Missense_Mutation

c.379G>A

p.Glu127Lys

p.E127K

Q8WW12

protein_coding

deleterious(0)

possibly_damaging(0.828)

TCGA-44-A47A-01

Lung

lung adenocarcinoma

Female

>=65

I/II

Unknown

PCNP

SNV

Missense_Mutation

c.144C>A

p.Ser48Arg

p.S48R

Q8WW12

protein_coding

tolerated_low_confidence(0.06)

probably_damaging(0.918)

TCGA-49-4507-01

Lung

lung adenocarcinoma

Female

>=65

III/IV

Chemotherapy

taxol

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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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