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: PRKX

Gene summary for PRKX

Gene summary.

Gene information	Species	Human
	Gene symbol	PRKX
	Gene ID	5613
	Gene name	protein kinase X-linked
	Gene Alias	PKX1
	Cytomap	Xp22.33
	Gene Type	protein-coding
	GO ID	GO:0001525
	UniProtAcc	A0A024RBU5

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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
5613	PRKX	AEH-subject5	Human	Endometrium	AEH	1.63e-34	8.30e-01	-0.2953
5613	PRKX	EEC-subject4	Human	Endometrium	EEC	9.54e-11	5.04e-01	-0.2571
5613	PRKX	EEC-subject5	Human	Endometrium	EEC	2.83e-04	-1.79e-01	-0.249
5613	PRKX	GSM5276934	Human	Endometrium	EEC	8.54e-07	-2.04e-01	-0.0913
5613	PRKX	GSM6177620_NYU_UCEC1_lib1_lib1	Human	Endometrium	EEC	6.49e-08	1.72e-01	-0.1869
5613	PRKX	GSM6177620_NYU_UCEC1_lib2_lib2	Human	Endometrium	EEC	2.26e-04	1.04e-01	-0.1875
5613	PRKX	GSM6177620_NYU_UCEC1_lib3_lib3	Human	Endometrium	EEC	8.25e-06	5.06e-02	-0.1883
5613	PRKX	GSM6177621_NYU_UCEC2_lib1_lib1	Human	Endometrium	EEC	3.71e-08	-3.79e-02	-0.1934
5613	PRKX	GSM6177622_NYU_UCEC3_lib1_lib1	Human	Endometrium	EEC	5.28e-15	1.18e-01	-0.1917
5613	PRKX	GSM6177622_NYU_UCEC3_lib2_lib2	Human	Endometrium	EEC	2.20e-08	9.71e-02	-0.1916
5613	PRKX	LZE2T	Human	Esophagus	ESCC	1.09e-09	9.25e-01	0.082
5613	PRKX	LZE4T	Human	Esophagus	ESCC	1.49e-09	2.45e-01	0.0811
5613	PRKX	LZE7T	Human	Esophagus	ESCC	1.67e-10	5.64e-01	0.0667
5613	PRKX	LZE8T	Human	Esophagus	ESCC	1.33e-05	8.07e-02	0.067
5613	PRKX	LZE22T	Human	Esophagus	ESCC	1.47e-03	2.27e-01	0.068
5613	PRKX	LZE24T	Human	Esophagus	ESCC	1.58e-03	4.80e-02	0.0596
5613	PRKX	LZE21T	Human	Esophagus	ESCC	2.04e-11	4.95e-01	0.0655
5613	PRKX	P2T-E	Human	Esophagus	ESCC	8.01e-55	1.15e+00	0.1177
5613	PRKX	P4T-E	Human	Esophagus	ESCC	2.42e-34	9.79e-01	0.1323
5613	PRKX	P5T-E	Human	Esophagus	ESCC	1.74e-09	2.08e-01	0.1327

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:00315899	Endometrium	AEH	cell-substrate adhesion	87/2100	363/18723	3.51e-12	5.70e-10	87
GO:000166710	Endometrium	AEH	ameboidal-type cell migration	90/2100	475/18723	3.73e-07	1.57e-05	90
GO:00506738	Endometrium	AEH	epithelial cell proliferation	84/2100	437/18723	4.88e-07	1.94e-05	84
GO:009013014	Endometrium	AEH	tissue migration	73/2100	365/18723	5.79e-07	2.20e-05	73
GO:009013214	Endometrium	AEH	epithelium migration	72/2100	360/18723	6.90e-07	2.55e-05	72
GO:001063114	Endometrium	AEH	epithelial cell migration	71/2100	357/18723	1.02e-06	3.52e-05	71
GO:00016556	Endometrium	AEH	urogenital system development	67/2100	338/18723	2.30e-06	6.76e-05	67
GO:00720015	Endometrium	AEH	renal system development	61/2100	302/18723	3.43e-06	9.24e-05	61
GO:00605627	Endometrium	AEH	epithelial tube morphogenesis	63/2100	325/18723	9.63e-06	2.23e-04	63
GO:00435428	Endometrium	AEH	endothelial cell migration	55/2100	279/18723	2.11e-05	4.15e-04	55
GO:00018224	Endometrium	AEH	kidney development	57/2100	293/18723	2.25e-05	4.35e-04	57
GO:00609932	Endometrium	AEH	kidney morphogenesis	24/2100	93/18723	6.73e-05	1.04e-03	24
GO:00308564	Endometrium	AEH	regulation of epithelial cell differentiation	33/2100	154/18723	1.81e-04	2.32e-03	33
GO:00610052	Endometrium	AEH	cell differentiation involved in kidney development	15/2100	57/18723	1.20e-03	1.04e-02	15
GO:00358504	Endometrium	AEH	epithelial cell differentiation involved in kidney development	13/2100	47/18723	1.53e-03	1.26e-02	13
GO:2000696	Endometrium	AEH	regulation of epithelial cell differentiation involved in kidney development	7/2100	17/18723	1.55e-03	1.27e-02	7
GO:003009916	Endometrium	AEH	myeloid cell differentiation	62/2100	381/18723	1.67e-03	1.36e-02	62
GO:00181058	Endometrium	AEH	peptidyl-serine phosphorylation	50/2100	315/18723	7.20e-03	4.13e-02	50
GO:0001935	Endometrium	AEH	endothelial cell proliferation	33/2100	193/18723	8.99e-03	4.87e-02	33
GO:003158915	Endometrium	EEC	cell-substrate adhesion	87/2168	363/18723	1.95e-11	3.00e-09	87

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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

PRKX

SNV

Missense_Mutation

c.844N>A

p.Asp282Asn

p.D282N

P51817

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PRKX

SNV

Missense_Mutation

c.769C>A

p.Leu257Ile

p.L257I

P51817

protein_coding

tolerated(0.08)

probably_damaging(0.999)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PRKX

SNV

Missense_Mutation

c.178N>G

p.Phe60Val

p.F60V

P51817

protein_coding

deleterious(0)

probably_damaging(0.974)

TCGA-B6-A0X1-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PRKX

SNV

Missense_Mutation

rs141998823

c.910N>T

p.Arg304Cys

p.R304C

P51817

protein_coding

deleterious(0.01)

possibly_damaging(0.794)

TCGA-BH-A0EE-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

docetaxel

PRKX

SNV

Missense_Mutation

c.769N>A

p.Leu257Ile

p.L257I

P51817

protein_coding

tolerated(0.08)

probably_damaging(0.999)

TCGA-BH-A201-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PRKX

SNV

Missense_Mutation

rs770062921

c.481G>A

p.Glu161Lys

p.E161K

P51817

protein_coding

tolerated(0.06)

probably_damaging(0.91)

TCGA-VS-A959-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

PRKX

SNV

Missense_Mutation

novel

c.250N>A

p.Asp84Asn

p.D84N

P51817

protein_coding

deleterious(0.02)

probably_damaging(0.936)

TCGA-AA-3947-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

PRKX

SNV

Missense_Mutation

novel

c.995A>C

p.Asn332Thr

p.N332T

P51817

protein_coding

deleterious(0)

possibly_damaging(0.882)

TCGA-A5-A0G1-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

PRKX

SNV

Missense_Mutation

novel

c.385N>A

p.Val129Met

p.V129M

P51817

protein_coding

deleterious(0)

probably_damaging(0.943)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

PRKX

SNV

Missense_Mutation

c.1000N>A

p.Glu334Lys

p.E334K

P51817

protein_coding

deleterious(0.01)

benign(0.385)

TCGA-AP-A056-01

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
5613	PRKX	DRUGGABLE GENOME, KINASE, ENZYME, SERINE THREONINE KINASE	inhibitor	178101884	GSK-690693
5613	PRKX	DRUGGABLE GENOME, KINASE, ENZYME, SERINE THREONINE KINASE		FASUDIL	FASUDIL	22257127
5613	PRKX	DRUGGABLE GENOME, KINASE, ENZYME, SERINE THREONINE KINASE		PD-0166285	PD-0166285
5613	PRKX	DRUGGABLE GENOME, KINASE, ENZYME, SERINE THREONINE KINASE		GSK-269962A	GSK-269962A
5613	PRKX	DRUGGABLE GENOME, KINASE, ENZYME, SERINE THREONINE KINASE		DOVITINIB	DOVITINIB
5613	PRKX	DRUGGABLE GENOME, KINASE, ENZYME, SERINE THREONINE KINASE		PALBOCICLIB	PALBOCICLIB
5613	PRKX	DRUGGABLE GENOME, KINASE, ENZYME, SERINE THREONINE KINASE		681640	CHEMBL379975
5613	PRKX	DRUGGABLE GENOME, KINASE, ENZYME, SERINE THREONINE KINASE		CENISERTIB	CENISERTIB
5613	PRKX	DRUGGABLE GENOME, KINASE, ENZYME, SERINE THREONINE KINASE		GW843682X	GW843682X
5613	PRKX	DRUGGABLE GENOME, KINASE, ENZYME, SERINE THREONINE KINASE		Y-27632	Y-27632	22257127

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