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: PKN2

Gene summary for PKN2

Gene summary.

Gene information	Species	Human
	Gene symbol	PKN2
	Gene ID	5586
	Gene name	protein kinase N2
	Gene Alias	PAK2
	Cytomap	1p22.2
	Gene Type	protein-coding
	GO ID	GO:0000278
	UniProtAcc	Q16513

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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
5586	PKN2	CA_HPV_1	Human	Cervix	CC	2.09e-03	-1.54e-01	0.0264
5586	PKN2	CA_HPV_3	Human	Cervix	CC	4.43e-03	-1.74e-02	0.0414
5586	PKN2	CCI_1	Human	Cervix	CC	1.03e-02	1.19e+00	0.528
5586	PKN2	CCI_2	Human	Cervix	CC	9.29e-11	1.18e+00	0.5249
5586	PKN2	CCI_3	Human	Cervix	CC	3.81e-07	9.86e-01	0.516
5586	PKN2	T1	Human	Cervix	CC	1.21e-02	-2.39e-01	0.0918
5586	PKN2	HTA11_3410_2000001011	Human	Colorectum	AD	3.46e-16	-6.18e-01	0.0155
5586	PKN2	HTA11_3361_2000001011	Human	Colorectum	AD	3.23e-09	-5.59e-01	-0.1207
5586	PKN2	HTA11_5216_2000001011	Human	Colorectum	SER	7.10e-04	-6.38e-01	-0.1462
5586	PKN2	HTA11_7862_2000001011	Human	Colorectum	AD	1.62e-04	-6.91e-01	-0.0179
5586	PKN2	HTA11_866_3004761011	Human	Colorectum	AD	4.35e-17	-6.59e-01	0.096
5586	PKN2	HTA11_8622_2000001021	Human	Colorectum	SER	6.25e-07	-7.72e-01	0.0528
5586	PKN2	HTA11_10711_2000001011	Human	Colorectum	AD	1.08e-03	-4.27e-01	0.0338
5586	PKN2	HTA11_7696_3000711011	Human	Colorectum	AD	4.09e-04	-3.76e-01	0.0674
5586	PKN2	HTA11_6818_2000001021	Human	Colorectum	AD	4.56e-03	-5.51e-01	0.0588
5586	PKN2	HTA11_99999970781_79442	Human	Colorectum	MSS	1.16e-22	-6.47e-01	0.294
5586	PKN2	HTA11_99999971662_82457	Human	Colorectum	MSS	1.87e-08	-4.28e-01	0.3859
5586	PKN2	HTA11_99999973899_84307	Human	Colorectum	MSS	1.24e-03	-5.73e-01	0.2585
5586	PKN2	HTA11_99999974143_84620	Human	Colorectum	MSS	3.41e-23	-6.13e-01	0.3005
5586	PKN2	A001-C-207	Human	Colorectum	FAP	6.39e-04	-1.48e-01	0.1278

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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
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:001603210	Cervix	CC	viral process	109/2311	415/18723	5.40e-15	6.46e-12	109
GO:001905810	Cervix	CC	viral life cycle	87/2311	317/18723	2.20e-13	1.20e-10	87
GO:009013210	Cervix	CC	epithelium migration	90/2311	360/18723	2.45e-11	6.11e-09	90
GO:00016679	Cervix	CC	ameboidal-type cell migration	110/2311	475/18723	2.66e-11	6.36e-09	110
GO:001063110	Cervix	CC	epithelial cell migration	89/2311	357/18723	3.72e-11	8.54e-09	89
GO:009013010	Cervix	CC	tissue migration	90/2311	365/18723	5.42e-11	1.05e-08	90
GO:00452169	Cervix	CC	cell-cell junction organization	53/2311	200/18723	3.83e-08	2.53e-06	53
GO:00343298	Cervix	CC	cell junction assembly	88/2311	420/18723	3.42e-07	1.38e-05	88
GO:00070439	Cervix	CC	cell-cell junction assembly	39/2311	146/18723	1.86e-06	5.94e-05	39
GO:001907910	Cervix	CC	viral genome replication	35/2311	131/18723	6.11e-06	1.49e-04	35
GO:00457876	Cervix	CC	positive regulation of cell cycle	66/2311	313/18723	7.78e-06	1.81e-04	66
GO:00073466	Cervix	CC	regulation of mitotic cell cycle	88/2311	457/18723	1.26e-05	2.60e-04	88
GO:00432978	Cervix	CC	apical junction assembly	24/2311	78/18723	1.36e-05	2.73e-04	24
GO:00459316	Cervix	CC	positive regulation of mitotic cell cycle	32/2311	121/18723	1.88e-05	3.47e-04	32
GO:00181057	Cervix	CC	peptidyl-serine phosphorylation	63/2311	315/18723	6.65e-05	9.47e-04	63
GO:005079210	Cervix	CC	regulation of viral process	38/2311	164/18723	8.12e-05	1.10e-03	38
GO:00900685	Cervix	CC	positive regulation of cell cycle process	50/2311	236/18723	8.25e-05	1.11e-03	50
GO:00182096	Cervix	CC	peptidyl-serine modification	66/2311	338/18723	9.58e-05	1.25e-03	66
GO:00513021	Cervix	CC	regulation of cell division	39/2311	177/18723	2.05e-04	2.33e-03	39
GO:190390010	Cervix	CC	regulation of viral life cycle	33/2311	148/18723	4.86e-04	4.76e-03	33

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0513533	Lung	AIS	Yersinia infection	30/961	137/8465	2.70e-04	2.92e-03	1.87e-03	30
hsa0415131	Lung	AIS	PI3K-Akt signaling pathway	57/961	354/8465	3.72e-03	2.00e-02	1.28e-02	57
hsa0513520	Oral cavity	OSCC	Yersinia infection	94/3704	137/8465	2.85e-09	3.08e-08	1.57e-08	94
hsa046218	Oral cavity	OSCC	NOD-like receptor signaling pathway	108/3704	186/8465	5.13e-05	2.07e-04	1.05e-04	108
hsa041516	Oral cavity	OSCC	PI3K-Akt signaling pathway	185/3704	354/8465	6.26e-04	1.86e-03	9.49e-04	185
hsa05135110	Oral cavity	OSCC	Yersinia infection	94/3704	137/8465	2.85e-09	3.08e-08	1.57e-08	94
hsa0462113	Oral cavity	OSCC	NOD-like receptor signaling pathway	108/3704	186/8465	5.13e-05	2.07e-04	1.05e-04	108
hsa0415113	Oral cavity	OSCC	PI3K-Akt signaling pathway	185/3704	354/8465	6.26e-04	1.86e-03	9.49e-04	185
hsa0513544	Oral cavity	EOLP	Yersinia infection	44/1218	137/8465	8.88e-08	1.06e-06	6.27e-07	44
hsa046214	Oral cavity	EOLP	NOD-like receptor signaling pathway	48/1218	186/8465	2.51e-05	1.31e-04	7.70e-05	48
hsa0415123	Oral cavity	EOLP	PI3K-Akt signaling pathway	73/1218	354/8465	7.03e-04	2.69e-03	1.59e-03	73
hsa0513554	Oral cavity	EOLP	Yersinia infection	44/1218	137/8465	8.88e-08	1.06e-06	6.27e-07	44
hsa046215	Oral cavity	EOLP	NOD-like receptor signaling pathway	48/1218	186/8465	2.51e-05	1.31e-04	7.70e-05	48
hsa0415133	Oral cavity	EOLP	PI3K-Akt signaling pathway	73/1218	354/8465	7.03e-04	2.69e-03	1.59e-03	73
hsa0415141	Oral cavity	NEOLP	PI3K-Akt signaling pathway	79/1112	354/8465	8.42e-07	9.92e-06	6.24e-06	79
hsa0513561	Oral cavity	NEOLP	Yersinia infection	33/1112	137/8465	3.20e-04	2.00e-03	1.26e-03	33
hsa046216	Oral cavity	NEOLP	NOD-like receptor signaling pathway	39/1112	186/8465	1.79e-03	7.91e-03	4.98e-03	39
hsa0415151	Oral cavity	NEOLP	PI3K-Akt signaling pathway	79/1112	354/8465	8.42e-07	9.92e-06	6.24e-06	79
hsa0513571	Oral cavity	NEOLP	Yersinia infection	33/1112	137/8465	3.20e-04	2.00e-03	1.26e-03	33
hsa046217	Oral cavity	NEOLP	NOD-like receptor signaling pathway	39/1112	186/8465	1.79e-03	7.91e-03	4.98e-03	39

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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

PKN2

SNV

Missense_Mutation

c.1450N>A

p.Glu484Lys

p.E484K

Q16513

protein_coding

deleterious(0)

probably_damaging(0.985)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

PKN2

SNV

Missense_Mutation

rs200905692

c.2900C>T

p.Ser967Leu

p.S967L

Q16513

protein_coding

tolerated(0.07)

benign(0.003)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PKN2

SNV

Missense_Mutation

c.164A>C

p.Glu55Ala

p.E55A

Q16513

protein_coding

tolerated(0.32)

probably_damaging(0.989)

TCGA-AR-A1AU-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

PKN2

SNV

Missense_Mutation

c.2692N>T

p.Arg898Trp

p.R898W

Q16513

protein_coding

deleterious(0)

possibly_damaging(0.727)

TCGA-BH-A0DK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

PKN2

SNV

Missense_Mutation

c.2479G>A

p.Glu827Lys

p.E827K

Q16513

protein_coding

deleterious(0)

probably_damaging(0.98)

TCGA-C8-A26Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PKN2

SNV

Missense_Mutation

c.2479N>C

p.Glu827Gln

p.E827Q

Q16513

protein_coding

deleterious(0)

probably_damaging(0.932)

TCGA-D8-A1JD-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

PKN2

SNV

Missense_Mutation

novel

c.2371N>A

p.Asp791Asn

p.D791N

Q16513

protein_coding

deleterious(0.01)

probably_damaging(0.971)

TCGA-S3-AA17-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

anastrozole

PKN2

insertion

Frame_Shift_Ins

novel

c.463_464insTCAAGACTAGCCTGGCCAAGATGGTGAAACC

p.Ala155ValfsTer57

p.A155Vfs*57

Q16513

protein_coding

TCGA-A2-A0EY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

PKN2

insertion

Frame_Shift_Ins

novel

c.232_233insACATACAAAT

p.Ser78AsnfsTer17

p.S78Nfs*17

Q16513

protein_coding

TCGA-AC-A3QQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PKN2

insertion

Frame_Shift_Ins

novel

c.1148_1149insC

p.Leu384SerfsTer5

p.L384Sfs*5

Q16513

protein_coding

TCGA-AC-A3QQ-01

Breast

breast invasive 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
5586	PKN2	DRUGGABLE GENOME, KINASE, ENZYME, SERINE THREONINE KINASE		PF-562271	PF-00562271
5586	PKN2	DRUGGABLE GENOME, KINASE, ENZYME, SERINE THREONINE KINASE		ERLOTINIB	ERLOTINIB
5586	PKN2	DRUGGABLE GENOME, KINASE, ENZYME, SERINE THREONINE KINASE		DOVITINIB	DOVITINIB
5586	PKN2	DRUGGABLE GENOME, KINASE, ENZYME, SERINE THREONINE KINASE		BAY-613606	CHEMBL541400
5586	PKN2	DRUGGABLE GENOME, KINASE, ENZYME, SERINE THREONINE KINASE	inhibitor	178101973
5586	PKN2	DRUGGABLE GENOME, KINASE, ENZYME, SERINE THREONINE KINASE		ENTRECTINIB	ENTRECTINIB
5586	PKN2	DRUGGABLE GENOME, KINASE, ENZYME, SERINE THREONINE KINASE		RG-1530	RG-1530
5586	PKN2	DRUGGABLE GENOME, KINASE, ENZYME, SERINE THREONINE KINASE		ILORASERTIB	ILORASERTIB
5586	PKN2	DRUGGABLE GENOME, KINASE, ENZYME, SERINE THREONINE KINASE		681640	CHEMBL379975
5586	PKN2	DRUGGABLE GENOME, KINASE, ENZYME, SERINE THREONINE KINASE		DASATINIB	DASATINIB

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