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: PNN

Gene summary for PNN

Gene summary.

Gene information	Species	Human
	Gene symbol	PNN
	Gene ID	5411
	Gene name	pinin, desmosome associated protein
	Gene Alias	DRS
	Cytomap	14q21.1
	Gene Type	protein-coding
	GO ID	GO:0000375
	UniProtAcc	Q9H307

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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
5411	PNN	HTA11_3410_2000001011	Human	Colorectum	AD	2.11e-10	-4.83e-01	0.0155
5411	PNN	HTA11_6818_2000001021	Human	Colorectum	AD	1.53e-02	-3.41e-01	0.0588
5411	PNN	A002-C-010	Human	Colorectum	FAP	1.23e-02	-6.47e-02	0.242
5411	PNN	A015-C-203	Human	Colorectum	FAP	3.86e-17	-5.39e-02	-0.1294
5411	PNN	A002-C-201	Human	Colorectum	FAP	5.42e-06	-4.42e-02	0.0324
5411	PNN	A001-C-119	Human	Colorectum	FAP	4.12e-02	-3.61e-02	-0.1557
5411	PNN	A001-C-108	Human	Colorectum	FAP	6.41e-13	2.48e-01	-0.0272
5411	PNN	A002-C-205	Human	Colorectum	FAP	1.33e-14	1.11e-01	-0.1236
5411	PNN	A001-C-104	Human	Colorectum	FAP	1.65e-05	3.08e-01	0.0184
5411	PNN	A015-C-006	Human	Colorectum	FAP	7.67e-21	5.29e-01	-0.0994
5411	PNN	A015-C-106	Human	Colorectum	FAP	9.87e-09	2.18e-01	-0.0511
5411	PNN	A002-C-114	Human	Colorectum	FAP	1.62e-13	2.16e-01	-0.1561
5411	PNN	A015-C-104	Human	Colorectum	FAP	4.33e-23	2.03e-01	-0.1899
5411	PNN	A001-C-014	Human	Colorectum	FAP	2.41e-07	1.33e-02	0.0135
5411	PNN	A002-C-016	Human	Colorectum	FAP	1.94e-14	4.37e-02	0.0521
5411	PNN	A015-C-002	Human	Colorectum	FAP	7.00e-04	-6.28e-02	-0.0763
5411	PNN	A001-C-007	Human	Colorectum	CRC	2.40e-05	5.60e-01	0.1899
5411	PNN	A001-C-203	Human	Colorectum	FAP	8.61e-04	3.48e-02	-0.0481
5411	PNN	A002-C-116	Human	Colorectum	FAP	1.75e-22	-1.75e-01	-0.0452
5411	PNN	A014-C-008	Human	Colorectum	FAP	1.40e-09	1.36e-01	-0.191

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:0008380	Colorectum	AD	RNA splicing	169/3918	434/18723	3.59e-18	2.04e-15	169
GO:0000377	Colorectum	AD	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	130/3918	320/18723	5.88e-16	2.16e-13	130
GO:0000398	Colorectum	AD	mRNA splicing, via spliceosome	130/3918	320/18723	5.88e-16	2.16e-13	130
GO:0000375	Colorectum	AD	RNA splicing, via transesterification reactions	131/3918	324/18723	7.11e-16	2.22e-13	131
GO:00083804	Colorectum	FAP	RNA splicing	108/2622	434/18723	7.90e-10	1.86e-07	108
GO:00003754	Colorectum	FAP	RNA splicing, via transesterification reactions	84/2622	324/18723	8.06e-09	1.10e-06	84
GO:00003774	Colorectum	FAP	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	83/2622	320/18723	9.66e-09	1.23e-06	83
GO:00003984	Colorectum	FAP	mRNA splicing, via spliceosome	83/2622	320/18723	9.66e-09	1.23e-06	83
GO:00083805	Colorectum	CRC	RNA splicing	90/2078	434/18723	2.80e-09	7.97e-07	90
GO:00003775	Colorectum	CRC	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	66/2078	320/18723	4.39e-07	3.37e-05	66
GO:00003985	Colorectum	CRC	mRNA splicing, via spliceosome	66/2078	320/18723	4.39e-07	3.37e-05	66
GO:00003755	Colorectum	CRC	RNA splicing, via transesterification reactions	66/2078	324/18723	7.00e-07	4.61e-05	66
GO:000838016	Endometrium	AEH	RNA splicing	111/2100	434/18723	2.42e-17	1.12e-14	111
GO:000037515	Endometrium	AEH	RNA splicing, via transesterification reactions	88/2100	324/18723	1.11e-15	3.91e-13	88
GO:000037715	Endometrium	AEH	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	87/2100	320/18723	1.51e-15	4.78e-13	87
GO:000039815	Endometrium	AEH	mRNA splicing, via spliceosome	87/2100	320/18723	1.51e-15	4.78e-13	87
GO:000838017	Endometrium	EEC	RNA splicing	111/2168	434/18723	2.45e-16	1.13e-13	111
GO:000037516	Endometrium	EEC	RNA splicing, via transesterification reactions	88/2168	324/18723	7.46e-15	2.63e-12	88
GO:000037716	Endometrium	EEC	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	87/2168	320/18723	9.97e-15	3.15e-12	87
GO:000039816	Endometrium	EEC	mRNA splicing, via spliceosome	87/2168	320/18723	9.97e-15	3.15e-12	87

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa03015	Colorectum	AD	mRNA surveillance pathway	35/2092	97/8465	7.95e-03	3.13e-02	2.00e-02	35
hsa030151	Colorectum	AD	mRNA surveillance pathway	35/2092	97/8465	7.95e-03	3.13e-02	2.00e-02	35
hsa030152	Colorectum	FAP	mRNA surveillance pathway	26/1404	97/8465	7.11e-03	2.64e-02	1.60e-02	26
hsa030153	Colorectum	FAP	mRNA surveillance pathway	26/1404	97/8465	7.11e-03	2.64e-02	1.60e-02	26
hsa0301321	Esophagus	ESCC	Nucleocytoplasmic transport	89/4205	108/8465	1.20e-12	2.37e-11	1.21e-11	89
hsa0301524	Esophagus	ESCC	mRNA surveillance pathway	72/4205	97/8465	6.12e-07	4.10e-06	2.10e-06	72
hsa0301331	Esophagus	ESCC	Nucleocytoplasmic transport	89/4205	108/8465	1.20e-12	2.37e-11	1.21e-11	89
hsa0301534	Esophagus	ESCC	mRNA surveillance pathway	72/4205	97/8465	6.12e-07	4.10e-06	2.10e-06	72
hsa030154	Liver	Cirrhotic	mRNA surveillance pathway	46/2530	97/8465	1.92e-04	1.30e-03	8.03e-04	46
hsa0301511	Liver	Cirrhotic	mRNA surveillance pathway	46/2530	97/8465	1.92e-04	1.30e-03	8.03e-04	46
hsa03013	Liver	HCC	Nucleocytoplasmic transport	81/4020	108/8465	4.28e-09	6.83e-08	3.80e-08	81
hsa0301521	Liver	HCC	mRNA surveillance pathway	66/4020	97/8465	3.16e-05	1.88e-04	1.04e-04	66
hsa030131	Liver	HCC	Nucleocytoplasmic transport	81/4020	108/8465	4.28e-09	6.83e-08	3.80e-08	81
hsa0301531	Liver	HCC	mRNA surveillance pathway	66/4020	97/8465	3.16e-05	1.88e-04	1.04e-04	66
hsa030136	Oral cavity	OSCC	Nucleocytoplasmic transport	82/3704	108/8465	7.93e-12	1.33e-10	6.77e-11	82
hsa030158	Oral cavity	OSCC	mRNA surveillance pathway	75/3704	97/8465	1.30e-11	2.01e-10	1.02e-10	75
hsa0301311	Oral cavity	OSCC	Nucleocytoplasmic transport	82/3704	108/8465	7.93e-12	1.33e-10	6.77e-11	82
hsa0301513	Oral cavity	OSCC	mRNA surveillance pathway	75/3704	97/8465	1.30e-11	2.01e-10	1.02e-10	75
hsa0301523	Oral cavity	LP	mRNA surveillance pathway	50/2418	97/8465	1.39e-06	1.50e-05	9.66e-06	50
hsa030132	Oral cavity	LP	Nucleocytoplasmic transport	53/2418	108/8465	4.68e-06	4.10e-05	2.64e-05	53

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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

PNN

SNV

Missense_Mutation

novel

c.95G>A

p.Arg32Gln

p.R32Q

Q9H307

protein_coding

deleterious(0.01)

probably_damaging(0.96)

TCGA-A2-A0CL-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

PNN

SNV

Missense_Mutation

rs866120482

c.793N>A

p.Ala265Thr

p.A265T

Q9H307

protein_coding

tolerated(0.1)

possibly_damaging(0.526)

TCGA-A8-A09X-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

PNN

SNV

Missense_Mutation

c.230N>C

p.Arg77Thr

p.R77T

Q9H307

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PNN

SNV

Missense_Mutation

rs747455268

c.506N>A

p.Arg169Gln

p.R169Q

Q9H307

protein_coding

tolerated(0.05)

possibly_damaging(0.546)

TCGA-D8-A1XJ-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

tamoxiphen

PNN

deletion

Frame_Shift_Del

novel

c.1051_1052delNN

p.Lys351ArgfsTer14

p.K351Rfs*14

Q9H307

protein_coding

TCGA-AR-A5QN-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

taxotere

PNN

SNV

Missense_Mutation

novel

c.1384G>C

p.Glu462Gln

p.E462Q

Q9H307

protein_coding

tolerated_low_confidence(0.62)

benign(0.005)

TCGA-C5-A2LX-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

PNN

SNV

Missense_Mutation

c.289N>T

p.Arg97Cys

p.R97C

Q9H307

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-EA-A410-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

PNN

SNV

Missense_Mutation

c.640G>C

p.Glu214Gln

p.E214Q

Q9H307

protein_coding

deleterious(0.03)

possibly_damaging(0.771)

TCGA-IR-A3LH-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

PNN

SNV

Missense_Mutation

c.1704N>G

p.Asn568Lys

p.N568K

Q9H307

protein_coding

deleterious_low_confidence(0.05)

possibly_damaging(0.736)

TCGA-LP-A7HU-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

PNN

SNV

Missense_Mutation

novel

c.1951N>A

p.Asp651Asn

p.D651N

Q9H307

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.602)

TCGA-VS-A9U6-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

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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