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: PRKD1

Gene summary for PRKD1

Gene summary.

Gene information	Species	Human
	Gene symbol	PRKD1
	Gene ID	5587
	Gene name	protein kinase D1
	Gene Alias	CHDED
	Cytomap	14q12
	Gene Type	protein-coding
	GO ID	GO:0001503
	UniProtAcc	F8WBA3

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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
5587	PRKD1	AEH-subject1	Human	Endometrium	AEH	3.01e-12	3.58e-01	-0.3059
5587	PRKD1	AEH-subject4	Human	Endometrium	AEH	2.72e-03	3.02e-01	-0.2657
5587	PRKD1	AEH-subject5	Human	Endometrium	AEH	5.98e-04	2.86e-01	-0.2953
5587	PRKD1	EEC-subject1	Human	Endometrium	EEC	1.75e-03	2.70e-01	-0.2682
5587	PRKD1	RNA-P17T-P17T-2	Human	Lung	IAC	5.18e-04	6.70e-01	0.3371
5587	PRKD1	RNA-P17T-P17T-4	Human	Lung	IAC	7.57e-03	6.29e-01	0.343
5587	PRKD1	RNA-P17T-P17T-6	Human	Lung	IAC	4.91e-03	6.04e-01	0.3385
5587	PRKD1	RNA-P25T1-P25T1-1	Human	Lung	AIS	4.47e-19	8.93e-01	-0.2116
5587	PRKD1	RNA-P25T1-P25T1-2	Human	Lung	AIS	1.25e-07	8.28e-01	-0.1941
5587	PRKD1	RNA-P25T1-P25T1-3	Human	Lung	AIS	2.19e-08	8.45e-01	-0.2107
5587	PRKD1	RNA-P25T1-P25T1-4	Human	Lung	AIS	6.51e-18	9.13e-01	-0.2119
5587	PRKD1	RNA-P7T1-P7T1-1	Human	Lung	AIS	9.18e-03	5.86e-01	-0.0961
5587	PRKD1	RNA-P7T1-P7T1-2	Human	Lung	AIS	7.80e-07	6.31e-01	-0.0876
5587	PRKD1	RNA-P7T1-P7T1-3	Human	Lung	AIS	2.76e-06	7.19e-01	-0.0822
5587	PRKD1	RNA-P7T1-P7T1-4	Human	Lung	AIS	2.18e-07	6.32e-01	-0.0809
5587	PRKD1	RNA-P8T2-P8T2-3	Human	Lung	AIS	1.91e-04	8.96e-01	-0.1284
5587	PRKD1	HTA12-15-2	Human	Pancreas	PDAC	4.41e-04	3.11e-01	0.2315
5587	PRKD1	HTA12-25-1	Human	Pancreas	PDAC	3.33e-07	5.55e-01	0.313
5587	PRKD1	HTA12-26-1	Human	Pancreas	PDAC	4.88e-07	4.50e-01	0.3728
5587	PRKD1	HTA12-29-1	Human	Pancreas	PDAC	1.02e-28	6.89e-01	0.3722

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Endometrium		AEH: Atypical endometrial hyperplasia
Endometrium		EEC: Endometrioid Cancer
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
Prostate		BPH: Benign Prostatic Hyperplasia

∗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:00321036	Endometrium	AEH	positive regulation of response to external stimulus	68/2100	427/18723	1.82e-03	1.44e-02	68
GO:003166810	Endometrium	AEH	cellular response to extracellular stimulus	43/2100	246/18723	2.10e-03	1.63e-02	43
GO:00181077	Endometrium	AEH	peptidyl-threonine phosphorylation	24/2100	116/18723	2.14e-03	1.65e-02	24
GO:00425949	Endometrium	AEH	response to starvation	36/2100	197/18723	2.15e-03	1.65e-02	36
GO:00510905	Endometrium	AEH	regulation of DNA-binding transcription factor activity	69/2100	440/18723	2.51e-03	1.87e-02	69
GO:00170389	Endometrium	AEH	protein import	37/2100	206/18723	2.56e-03	1.89e-02	37
GO:00182107	Endometrium	AEH	peptidyl-threonine modification	25/2100	125/18723	2.84e-03	2.04e-02	25
GO:00456692	Endometrium	AEH	positive regulation of osteoblast differentiation	16/2100	69/18723	3.46e-03	2.39e-02	16
GO:00435342	Endometrium	AEH	blood vessel endothelial cell migration	32/2100	176/18723	3.97e-03	2.66e-02	32
GO:00192165	Endometrium	AEH	regulation of lipid metabolic process	53/2100	331/18723	4.86e-03	3.07e-02	53
GO:19045916	Endometrium	AEH	positive regulation of protein import	11/2100	43/18723	6.60e-03	3.89e-02	11
GO:00181058	Endometrium	AEH	peptidyl-serine phosphorylation	50/2100	315/18723	7.20e-03	4.13e-02	50
GO:00509214	Endometrium	AEH	positive regulation of chemotaxis	26/2100	141/18723	7.31e-03	4.18e-02	26
GO:19045897	Endometrium	AEH	regulation of protein import	14/2100	63/18723	8.93e-03	4.84e-02	14
GO:0001935	Endometrium	AEH	endothelial cell proliferation	33/2100	193/18723	8.99e-03	4.87e-02	33
GO:19040623	Endometrium	AEH	regulation of cation transmembrane transport	55/2100	357/18723	9.18e-03	4.96e-02	55
GO:003164717	Endometrium	EEC	regulation of protein stability	80/2168	298/18723	2.48e-13	5.96e-11	80
GO:000989617	Endometrium	EEC	positive regulation of catabolic process	108/2168	492/18723	2.55e-11	3.64e-09	108
GO:000697917	Endometrium	EEC	response to oxidative stress	99/2168	446/18723	9.02e-11	1.13e-08	99
GO:007259415	Endometrium	EEC	establishment of protein localization to organelle	94/2168	422/18723	2.22e-10	2.51e-08	94

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0520826	Endometrium	AEH	Chemical carcinogenesis - reactive oxygen species	91/1197	223/8465	3.28e-23	1.33e-21	9.76e-22	91
hsa0401514	Endometrium	AEH	Rap1 signaling pathway	49/1197	210/8465	2.03e-04	1.78e-03	1.30e-03	49
hsa05208112	Endometrium	AEH	Chemical carcinogenesis - reactive oxygen species	91/1197	223/8465	3.28e-23	1.33e-21	9.76e-22	91
hsa0401515	Endometrium	AEH	Rap1 signaling pathway	49/1197	210/8465	2.03e-04	1.78e-03	1.30e-03	49
hsa0520827	Endometrium	EEC	Chemical carcinogenesis - reactive oxygen species	94/1237	223/8465	4.11e-24	1.93e-22	1.44e-22	94
hsa0401522	Endometrium	EEC	Rap1 signaling pathway	49/1237	210/8465	4.45e-04	3.47e-03	2.59e-03	49
hsa0520836	Endometrium	EEC	Chemical carcinogenesis - reactive oxygen species	94/1237	223/8465	4.11e-24	1.93e-22	1.44e-22	94
hsa0401532	Endometrium	EEC	Rap1 signaling pathway	49/1237	210/8465	4.45e-04	3.47e-03	2.59e-03	49
hsa0520816	Lung	IAC	Chemical carcinogenesis - reactive oxygen species	51/1053	223/8465	8.45e-06	2.14e-04	1.42e-04	51
hsa0401510	Lung	IAC	Rap1 signaling pathway	41/1053	210/8465	2.01e-03	1.07e-02	7.10e-03	41
hsa0520817	Lung	IAC	Chemical carcinogenesis - reactive oxygen species	51/1053	223/8465	8.45e-06	2.14e-04	1.42e-04	51
hsa0401511	Lung	IAC	Rap1 signaling pathway	41/1053	210/8465	2.01e-03	1.07e-02	7.10e-03	41
hsa0520823	Lung	AIS	Chemical carcinogenesis - reactive oxygen species	47/961	223/8465	1.63e-05	3.77e-04	2.41e-04	47
hsa0401521	Lung	AIS	Rap1 signaling pathway	41/961	210/8465	3.23e-04	3.38e-03	2.16e-03	41
hsa0520833	Lung	AIS	Chemical carcinogenesis - reactive oxygen species	47/961	223/8465	1.63e-05	3.77e-04	2.41e-04	47
hsa0401531	Lung	AIS	Rap1 signaling pathway	41/961	210/8465	3.23e-04	3.38e-03	2.16e-03	41
hsa0520828	Prostate	BPH	Chemical carcinogenesis - reactive oxygen species	114/1718	223/8465	3.05e-25	1.44e-23	8.91e-24	114
hsa0401516	Prostate	BPH	Rap1 signaling pathway	61/1718	210/8465	1.40e-03	5.85e-03	3.62e-03	61
hsa05208113	Prostate	BPH	Chemical carcinogenesis - reactive oxygen species	114/1718	223/8465	3.05e-25	1.44e-23	8.91e-24	114
hsa0401517	Prostate	BPH	Rap1 signaling pathway	61/1718	210/8465	1.40e-03	5.85e-03	3.62e-03	61

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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

PRKD1

SNV

Missense_Mutation

novel

c.865C>T

p.Pro289Ser

p.P289S

protein_coding

deleterious(0)

probably_damaging(0.995)

TCGA-AC-A6IX-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

PRKD1

SNV

Missense_Mutation

c.1780N>C

p.Asp594His

p.D594H

protein_coding

deleterious(0)

probably_damaging(0.916)

TCGA-AR-A1AI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

PRKD1

SNV

Missense_Mutation

novel

c.1466N>T

p.Ala489Val

p.A489V

protein_coding

tolerated(0.18)

benign(0.009)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

PRKD1

SNV

Missense_Mutation

novel

c.950A>G

p.His317Arg

p.H317R

protein_coding

deleterious(0.01)

probably_damaging(0.998)

TCGA-BH-A8FY-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PRKD1

SNV

Missense_Mutation

rs368595371

c.314N>A

p.Arg105His

p.R105H

protein_coding

deleterious(0.02)

benign(0.349)

TCGA-D8-A1XQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PRKD1

SNV

Missense_Mutation

c.766A>G

p.Asn256Asp

p.N256D

protein_coding

tolerated(0.33)

benign(0.022)

TCGA-GM-A2DB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxol

PRKD1

SNV

Missense_Mutation

novel

c.2488N>T

p.Val830Leu

p.V830L

protein_coding

deleterious(0)

benign(0.272)

TCGA-LL-A6FQ-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

PRKD1

insertion

Nonsense_Mutation

novel

c.2582_2583insTTCTGTTTGGTGTGTCCCATTGGTGTTGTCATTGTAAA

p.Lys862SerfsTer12

p.K862Sfs*12

protein_coding

TCGA-A2-A0EY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

PRKD1

insertion

Nonsense_Mutation

novel

c.2356_2357insCTTACAGCTGATAGAGCTCTAAAACAAT

p.Ser786ThrfsTer4

p.S786Tfs*4

protein_coding

TCGA-AN-A04A-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

PRKD1

SNV

Missense_Mutation

c.2710N>A

p.Glu904Lys

p.E904K

protein_coding

tolerated_low_confidence(0.66)

benign(0.015)

TCGA-DG-A2KK-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

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
5587	PRKD1	DRUGGABLE GENOME, KINASE, ENZYME, TRANSCRIPTION FACTOR, SERINE THREONINE KINASE	inhibitor	178102596
5587	PRKD1	DRUGGABLE GENOME, KINASE, ENZYME, TRANSCRIPTION FACTOR, SERINE THREONINE KINASE	inhibitor	SOPHORETIN	QUERCETIN
5587	PRKD1	DRUGGABLE GENOME, KINASE, ENZYME, TRANSCRIPTION FACTOR, SERINE THREONINE KINASE	inhibitor	249565728
5587	PRKD1	DRUGGABLE GENOME, KINASE, ENZYME, TRANSCRIPTION FACTOR, SERINE THREONINE KINASE	inhibitor	328083472
5587	PRKD1	DRUGGABLE GENOME, KINASE, ENZYME, TRANSCRIPTION FACTOR, SERINE THREONINE KINASE		RESVERATROL	RESVERATROL	11008129
5587	PRKD1	DRUGGABLE GENOME, KINASE, ENZYME, TRANSCRIPTION FACTOR, SERINE THREONINE KINASE	inhibitor	CHEMBL494089	GSK-690693
5587	PRKD1	DRUGGABLE GENOME, KINASE, ENZYME, TRANSCRIPTION FACTOR, SERINE THREONINE KINASE	inhibitor	348353640
5587	PRKD1	DRUGGABLE GENOME, KINASE, ENZYME, TRANSCRIPTION FACTOR, SERINE THREONINE KINASE		VASOPRESSIN	VASOPRESSIN	11514571
5587	PRKD1	DRUGGABLE GENOME, KINASE, ENZYME, TRANSCRIPTION FACTOR, SERINE THREONINE KINASE	inhibitor	CHEMBL608533	MIDOSTAURIN
5587	PRKD1	DRUGGABLE GENOME, KINASE, ENZYME, TRANSCRIPTION FACTOR, SERINE THREONINE KINASE	inhibitor	328083471

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