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: PRKCA

Gene summary for PRKCA

Gene summary.

Gene information	Species	Human
	Gene symbol	PRKCA
	Gene ID	5578
	Gene name	protein kinase C alpha
	Gene Alias	AAG6
	Cytomap	17q24.2
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	P17252

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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
5578	PRKCA	HSIL_HPV_2	Human	Cervix	HSIL_HPV	6.30e-03	3.07e-01	0.0208
5578	PRKCA	CCI_1	Human	Cervix	CC	6.87e-04	8.64e-01	0.528
5578	PRKCA	H2	Human	Cervix	HSIL_HPV	2.39e-05	-2.18e-01	0.0632
5578	PRKCA	HTA11_3410_2000001011	Human	Colorectum	AD	4.77e-10	-4.57e-01	0.0155
5578	PRKCA	HTA11_347_2000001011	Human	Colorectum	AD	2.59e-05	4.75e-01	-0.1954
5578	PRKCA	HTA11_1391_2000001011	Human	Colorectum	AD	1.08e-05	5.91e-01	-0.059
5578	PRKCA	HTA11_8622_2000001021	Human	Colorectum	SER	1.35e-03	-6.44e-01	0.0528
5578	PRKCA	HTA11_99999970781_79442	Human	Colorectum	MSS	6.75e-42	-8.39e-01	0.294
5578	PRKCA	HTA11_99999965104_69814	Human	Colorectum	MSS	2.39e-08	6.93e-01	0.281
5578	PRKCA	HTA11_99999974143_84620	Human	Colorectum	MSS	6.50e-04	-3.60e-01	0.3005
5578	PRKCA	F007	Human	Colorectum	FAP	3.54e-02	5.82e-02	0.1176
5578	PRKCA	A015-C-203	Human	Colorectum	FAP	7.05e-36	-5.33e-01	-0.1294
5578	PRKCA	A015-C-204	Human	Colorectum	FAP	7.31e-05	-3.55e-01	-0.0228
5578	PRKCA	A014-C-040	Human	Colorectum	FAP	5.25e-07	-6.10e-01	-0.1184
5578	PRKCA	A002-C-201	Human	Colorectum	FAP	7.79e-08	-1.77e-01	0.0324
5578	PRKCA	A001-C-119	Human	Colorectum	FAP	2.96e-05	-3.61e-01	-0.1557
5578	PRKCA	A001-C-108	Human	Colorectum	FAP	9.35e-14	-2.77e-01	-0.0272
5578	PRKCA	A002-C-205	Human	Colorectum	FAP	4.21e-26	-6.51e-01	-0.1236
5578	PRKCA	A015-C-006	Human	Colorectum	FAP	7.69e-18	-5.85e-01	-0.0994
5578	PRKCA	A015-C-106	Human	Colorectum	FAP	1.91e-08	-2.81e-01	-0.0511

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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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
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:003210323	Oral cavity	NEOLP	positive regulation of response to external stimulus	81/2005	427/18723	2.04e-07	6.74e-06	81
GO:000283131	Oral cavity	NEOLP	regulation of response to biotic stimulus	65/2005	327/18723	5.93e-07	1.74e-05	65
GO:007052722	Oral cavity	NEOLP	platelet aggregation	22/2005	67/18723	9.16e-07	2.46e-05	22
GO:004348732	Oral cavity	NEOLP	regulation of RNA stability	40/2005	170/18723	1.20e-06	3.12e-05	40
GO:005081722	Oral cavity	NEOLP	coagulation	48/2005	222/18723	1.51e-06	3.77e-05	48
GO:002240724	Oral cavity	NEOLP	regulation of cell-cell adhesion	81/2005	448/18723	1.54e-06	3.83e-05	81
GO:000759621	Oral cavity	NEOLP	blood coagulation	47/2005	217/18723	1.84e-06	4.44e-05	47
GO:003249631	Oral cavity	NEOLP	response to lipopolysaccharide	65/2005	343/18723	3.30e-06	7.40e-05	65
GO:000759921	Oral cavity	NEOLP	hemostasis	47/2005	222/18723	3.57e-06	7.85e-05	47
GO:005087825	Oral cavity	NEOLP	regulation of body fluid levels	70/2005	379/18723	3.62e-06	7.94e-05	70
GO:004354215	Oral cavity	NEOLP	endothelial cell migration	55/2005	279/18723	5.51e-06	1.13e-04	55
GO:000223731	Oral cavity	NEOLP	response to molecule of bacterial origin	67/2005	363/18723	5.94e-06	1.20e-04	67
GO:003465531	Oral cavity	NEOLP	nucleobase-containing compound catabolic process	73/2005	407/18723	6.69e-06	1.34e-04	73
GO:004593131	Oral cavity	NEOLP	positive regulation of mitotic cell cycle	30/2005	121/18723	8.28e-06	1.60e-04	30
GO:001063223	Oral cavity	NEOLP	regulation of epithelial cell migration	56/2005	292/18723	1.07e-05	1.98e-04	56
GO:190370632	Oral cavity	NEOLP	regulation of hemopoiesis	66/2005	367/18723	1.67e-05	2.83e-04	66
GO:000704318	Oral cavity	NEOLP	cell-cell junction assembly	33/2005	146/18723	2.42e-05	3.84e-04	33
GO:001810722	Oral cavity	NEOLP	peptidyl-threonine phosphorylation	28/2005	116/18723	2.78e-05	4.31e-04	28
GO:003016812	Oral cavity	NEOLP	platelet activation	29/2005	123/18723	3.23e-05	4.84e-04	29
GO:001063424	Oral cavity	NEOLP	positive regulation of epithelial cell migration	37/2005	176/18723	4.37e-05	6.14e-04	37

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0517120	Cervix	CC	Coronavirus disease - COVID-19	111/1267	232/8465	1.82e-33	5.90e-31	3.49e-31	111
hsa0541520	Cervix	CC	Diabetic cardiomyopathy	76/1267	203/8465	1.40e-15	6.46e-14	3.82e-14	76
hsa0502218	Cervix	CC	Pathways of neurodegeneration - multiple diseases	128/1267	476/8465	2.87e-12	9.29e-11	5.50e-11	128
hsa0541720	Cervix	CC	Lipid and atherosclerosis	65/1267	215/8465	6.47e-09	1.10e-07	6.52e-08	65
hsa0516318	Cervix	CC	Human cytomegalovirus infection	65/1267	225/8465	4.59e-08	6.47e-07	3.83e-07	65
hsa0520516	Cervix	CC	Proteoglycans in cancer	60/1267	205/8465	9.13e-08	1.18e-06	7.00e-07	60
hsa0451010	Cervix	CC	Focal adhesion	59/1267	203/8465	1.53e-07	1.84e-06	1.09e-06	59
hsa0467020	Cervix	CC	Leukocyte transendothelial migration	36/1267	114/8465	5.22e-06	4.83e-05	2.86e-05	36
hsa0401512	Cervix	CC	Rap1 signaling pathway	56/1267	210/8465	6.23e-06	5.61e-05	3.32e-05	56
hsa0466612	Cervix	CC	Fc gamma R-mediated phagocytosis	31/1267	97/8465	1.78e-05	1.42e-04	8.40e-05	31
hsa0472318	Cervix	CC	Retrograde endocannabinoid signaling	42/1267	148/8465	1.79e-05	1.42e-04	8.40e-05	42
hsa0517016	Cervix	CC	Human immunodeficiency virus 1 infection	55/1267	212/8465	1.80e-05	1.42e-04	8.40e-05	55
hsa0401210	Cervix	CC	ErbB signaling pathway	28/1267	85/8465	2.40e-05	1.82e-04	1.08e-04	28
hsa0407110	Cervix	CC	Sphingolipid signaling pathway	35/1267	121/8465	5.70e-05	3.93e-04	2.32e-04	35
hsa043609	Cervix	CC	Axon guidance	47/1267	182/8465	8.13e-05	5.38e-04	3.18e-04	47
hsa052148	Cervix	CC	Glioma	24/1267	75/8465	1.51e-04	9.20e-04	5.44e-04	24
hsa0511016	Cervix	CC	Vibrio cholerae infection	18/1267	50/8465	1.91e-04	1.11e-03	6.55e-04	18
hsa04664	Cervix	CC	Fc epsilon RI signaling pathway	22/1267	68/8465	2.35e-04	1.31e-03	7.77e-04	22
hsa043109	Cervix	CC	Wnt signaling pathway	43/1267	171/8465	3.03e-04	1.64e-03	9.68e-04	43
hsa0516414	Cervix	CC	Influenza A	43/1267	171/8465	3.03e-04	1.64e-03	9.68e-04	43

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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

PRKCA

SNV

Missense_Mutation

novel

c.756N>T

p.Arg252Ser

p.R252S

P17252

protein_coding

tolerated(0.14)

benign(0.1)

TCGA-A2-A25A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Cytoxan

PRKCA

SNV

Missense_Mutation

rs776243082

c.430N>A

p.Val144Ile

p.V144I

P17252

protein_coding

tolerated(0.19)

benign(0.059)

TCGA-A8-A06O-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

letrozole

PRKCA

SNV

Missense_Mutation

novel

c.1621N>A

p.Glu541Lys

p.E541K

P17252

protein_coding

deleterious(0.01)

benign(0.397)

TCGA-AN-A0FZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

PRKCA

insertion

Frame_Shift_Ins

novel

c.788_789insGGCA

p.Ser264AlafsTer17

p.S264Afs*17

P17252

protein_coding

TCGA-AO-A0JF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

PRKCA

insertion

Frame_Shift_Ins

novel

c.789_790insGATCTCAGCTCACTGCAGCCTCCGCC

p.Ser264AspfsTer12

p.S264Dfs*12

P17252

protein_coding

TCGA-AO-A0JF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

PRKCA

insertion

Nonsense_Mutation

novel

c.353_354insAATGATCCATTTAGGGTTGTTCTGTTCACTTCACAAACACACCGATT

p.Cys118Ter

p.C118*

P17252

protein_coding

TCGA-BH-A1FD-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PRKCA

SNV

Missense_Mutation

novel

c.1663N>A

p.Val555Ile

p.V555I

P17252

protein_coding

tolerated(0.07)

benign(0.213)

TCGA-HM-A3JJ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

PRKCA

SNV

Missense_Mutation

rs140466753

c.1895G>A

p.Arg632Gln

p.R632Q

P17252

protein_coding

tolerated(0.07)

benign(0.029)

TCGA-IR-A3LL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

PRKCA

SNV

Missense_Mutation

novel

c.1627G>A

p.Glu543Lys

p.E543K

P17252

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

PRKCA

SNV

Missense_Mutation

c.916N>A

p.Glu306Lys

p.E306K

P17252

protein_coding

tolerated(0.15)

benign(0.014)

TCGA-UC-A7PF-01

Cervix

cervical & endocervical cancer

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
5578	PRKCA	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, CLINICALLY ACTIONABLE, ENZYME	inhibitor	178102320	ENZASTAURIN
5578	PRKCA	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, CLINICALLY ACTIONABLE, ENZYME		BRYOSTATIN	BRYOSTATIN	22579485
5578	PRKCA	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, CLINICALLY ACTIONABLE, ENZYME	inhibitor	SOPHORETIN	QUERCETIN
5578	PRKCA	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, CLINICALLY ACTIONABLE, ENZYME		Sodium phenylbutyrate
5578	PRKCA	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, CLINICALLY ACTIONABLE, ENZYME	inhibitor	178101880
5578	PRKCA	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, CLINICALLY ACTIONABLE, ENZYME		hydrochlorothiazide	HYDROCHLOROTHIAZIDE
5578	PRKCA	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, CLINICALLY ACTIONABLE, ENZYME	inhibitor	MIDOSTAURIN	MIDOSTAURIN
5578	PRKCA	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, CLINICALLY ACTIONABLE, ENZYME		BRYOSTATIN-1
5578	PRKCA	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, CLINICALLY ACTIONABLE, ENZYME	inhibitor	178102596
5578	PRKCA	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, CLINICALLY ACTIONABLE, ENZYME		ENOXOLONE	ENOXOLONE	24461294

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