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: PRKCE

Gene summary for PRKCE

Gene summary.

Gene information	Species	Human
	Gene symbol	PRKCE
	Gene ID	5581
	Gene name	protein kinase C epsilon
	Gene Alias	PKCE
	Cytomap	2p21
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	L7RTI5

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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
5581	PRKCE	CCI_1	Human	Cervix	CC	9.93e-16	1.24e+00	0.528
5581	PRKCE	CCI_2	Human	Cervix	CC	5.53e-12	1.03e+00	0.5249
5581	PRKCE	CCI_3	Human	Cervix	CC	2.32e-10	7.08e-01	0.516
5581	PRKCE	HTA11_3410_2000001011	Human	Colorectum	AD	2.07e-11	-5.48e-01	0.0155
5581	PRKCE	HTA11_347_2000001011	Human	Colorectum	AD	1.24e-07	5.48e-01	-0.1954
5581	PRKCE	HTA11_99999970781_79442	Human	Colorectum	MSS	1.03e-26	-7.05e-01	0.294
5581	PRKCE	HTA11_99999971662_82457	Human	Colorectum	MSS	2.82e-04	-3.43e-01	0.3859
5581	PRKCE	A001-C-207	Human	Colorectum	FAP	2.46e-04	-3.66e-01	0.1278
5581	PRKCE	A015-C-203	Human	Colorectum	FAP	1.04e-33	-3.98e-01	-0.1294
5581	PRKCE	A015-C-204	Human	Colorectum	FAP	6.86e-05	-3.49e-01	-0.0228
5581	PRKCE	A014-C-040	Human	Colorectum	FAP	3.95e-03	-2.84e-01	-0.1184
5581	PRKCE	A002-C-201	Human	Colorectum	FAP	9.45e-11	-2.08e-01	0.0324
5581	PRKCE	A001-C-119	Human	Colorectum	FAP	4.01e-10	-6.88e-01	-0.1557
5581	PRKCE	A001-C-108	Human	Colorectum	FAP	9.71e-22	-4.77e-01	-0.0272
5581	PRKCE	A002-C-205	Human	Colorectum	FAP	1.14e-21	-4.04e-01	-0.1236
5581	PRKCE	A001-C-104	Human	Colorectum	FAP	9.84e-08	-4.17e-01	0.0184
5581	PRKCE	A015-C-006	Human	Colorectum	FAP	2.32e-19	-7.23e-01	-0.0994
5581	PRKCE	A015-C-106	Human	Colorectum	FAP	2.11e-13	-3.55e-01	-0.0511
5581	PRKCE	A002-C-114	Human	Colorectum	FAP	5.73e-18	-4.02e-01	-0.1561
5581	PRKCE	A015-C-104	Human	Colorectum	FAP	4.94e-39	-6.15e-01	-0.1899

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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
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
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:003139713	Lung	AIS	negative regulation of protein ubiquitination	22/1849	83/18723	1.22e-05	4.71e-04	22
GO:011005313	Lung	AIS	regulation of actin filament organization	50/1849	278/18723	2.13e-05	7.27e-04	50
GO:004325413	Lung	AIS	regulation of protein-containing complex assembly	68/1849	428/18723	5.51e-05	1.56e-03	68
GO:005123512	Lung	AIS	maintenance of location	55/1849	327/18723	5.93e-05	1.65e-03	55
GO:005125813	Lung	AIS	protein polymerization	51/1849	297/18723	6.29e-05	1.70e-03	51
GO:000974313	Lung	AIS	response to carbohydrate	45/1849	253/18723	7.09e-05	1.88e-03	45
GO:190230512	Lung	AIS	regulation of sodium ion transmembrane transport	18/1849	68/18723	7.53e-05	1.94e-03	18
GO:000166713	Lung	AIS	ameboidal-type cell migration	73/1849	475/18723	8.91e-05	2.20e-03	73
GO:200064912	Lung	AIS	regulation of sodium ion transmembrane transporter activity	16/1849	58/18723	1.09e-04	2.57e-03	16
GO:005165113	Lung	AIS	maintenance of location in cell	39/1849	214/18723	1.23e-04	2.81e-03	39
GO:003133413	Lung	AIS	positive regulation of protein-containing complex assembly	42/1849	237/18723	1.32e-04	2.97e-03	42
GO:003629313	Lung	AIS	response to decreased oxygen levels	53/1849	322/18723	1.42e-04	3.09e-03	53
GO:000202811	Lung	AIS	regulation of sodium ion transport	21/1849	90/18723	1.44e-04	3.13e-03	21
GO:003227113	Lung	AIS	regulation of protein polymerization	41/1849	233/18723	1.85e-04	3.83e-03	41
GO:00434101	Lung	AIS	positive regulation of MAPK cascade	72/1849	480/18723	2.11e-04	4.32e-03	72
GO:003629412	Lung	AIS	cellular response to decreased oxygen levels	31/1849	161/18723	2.15e-04	4.36e-03	31
GO:007145312	Lung	AIS	cellular response to oxygen levels	33/1849	177/18723	2.56e-04	4.96e-03	33
GO:000166613	Lung	AIS	response to hypoxia	50/1849	307/18723	2.79e-04	5.26e-03	50
GO:007145612	Lung	AIS	cellular response to hypoxia	29/1849	151/18723	3.54e-04	6.32e-03	29
GO:003428413	Lung	AIS	response to monosaccharide	39/1849	225/18723	3.59e-04	6.39e-03	39

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0513120	Cervix	CC	Shigellosis	69/1267	247/8465	7.64e-08	1.03e-06	6.10e-07	69
hsa0453020	Cervix	CC	Tight junction	49/1267	169/8465	1.87e-06	1.78e-05	1.05e-05	49
hsa0466612	Cervix	CC	Fc gamma R-mediated phagocytosis	31/1267	97/8465	1.78e-05	1.42e-04	8.40e-05	31
hsa0407110	Cervix	CC	Sphingolipid signaling pathway	35/1267	121/8465	5.70e-05	3.93e-04	2.32e-04	35
hsa049336	Cervix	CC	AGE-RAGE signaling pathway in diabetic complications	25/1267	100/8465	5.64e-03	1.88e-02	1.11e-02	25
hsa05131110	Cervix	CC	Shigellosis	69/1267	247/8465	7.64e-08	1.03e-06	6.10e-07	69
hsa04530110	Cervix	CC	Tight junction	49/1267	169/8465	1.87e-06	1.78e-05	1.05e-05	49
hsa0466613	Cervix	CC	Fc gamma R-mediated phagocytosis	31/1267	97/8465	1.78e-05	1.42e-04	8.40e-05	31
hsa0407113	Cervix	CC	Sphingolipid signaling pathway	35/1267	121/8465	5.70e-05	3.93e-04	2.32e-04	35
hsa0493313	Cervix	CC	AGE-RAGE signaling pathway in diabetic complications	25/1267	100/8465	5.64e-03	1.88e-02	1.11e-02	25
hsa05131	Colorectum	AD	Shigellosis	109/2092	247/8465	1.09e-11	2.44e-10	1.55e-10	109
hsa04530	Colorectum	AD	Tight junction	76/2092	169/8465	5.49e-09	9.69e-08	6.18e-08	76
hsa04666	Colorectum	AD	Fc gamma R-mediated phagocytosis	46/2092	97/8465	9.10e-07	1.22e-05	7.77e-06	46
hsa04071	Colorectum	AD	Sphingolipid signaling pathway	43/2092	121/8465	4.83e-03	2.28e-02	1.45e-02	43
hsa051311	Colorectum	AD	Shigellosis	109/2092	247/8465	1.09e-11	2.44e-10	1.55e-10	109
hsa045301	Colorectum	AD	Tight junction	76/2092	169/8465	5.49e-09	9.69e-08	6.18e-08	76
hsa046661	Colorectum	AD	Fc gamma R-mediated phagocytosis	46/2092	97/8465	9.10e-07	1.22e-05	7.77e-06	46
hsa040711	Colorectum	AD	Sphingolipid signaling pathway	43/2092	121/8465	4.83e-03	2.28e-02	1.45e-02	43
hsa051314	Colorectum	MSS	Shigellosis	94/1875	247/8465	6.82e-09	1.34e-07	8.23e-08	94
hsa046664	Colorectum	MSS	Fc gamma R-mediated phagocytosis	45/1875	97/8465	9.30e-08	1.56e-06	9.55e-07	45

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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

PRKCE

SNV

Missense_Mutation

novel

c.256G>A

p.Asp86Asn

p.D86N

Q02156

protein_coding

tolerated(0.07)

benign(0.36)

TCGA-3C-AALI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Poly E

Complete Response

PRKCE

SNV

Missense_Mutation

novel

c.404C>T

p.Ser135Leu

p.S135L

Q02156

protein_coding

tolerated(0.28)

benign(0.006)

TCGA-A7-A13F-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

PRKCE

SNV

Missense_Mutation

novel

c.1219N>A

p.Glu407Lys

p.E407K

Q02156

protein_coding

deleterious(0)

benign(0.017)

TCGA-AC-A6IW-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PRKCE

SNV

Missense_Mutation

c.1441N>A

p.Arg481Ser

p.R481S

Q02156

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PRKCE

SNV

Missense_Mutation

novel

c.634N>C

p.Cys212Arg

p.C212R

Q02156

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AN-A0FX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PRKCE

SNV

Missense_Mutation

c.202N>A

p.Glu68Lys

p.E68K

Q02156

protein_coding

tolerated(0.19)

benign(0.022)

TCGA-C8-A137-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PRKCE

SNV

Missense_Mutation

novel

c.79N>T

p.His27Tyr

p.H27Y

Q02156

protein_coding

deleterious(0.03)

possibly_damaging(0.898)

TCGA-E2-A2P6-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

PRKCE

insertion

Nonsense_Mutation

novel

c.2059_2060insACCTCGTAGGGCATTAGGATGAAATGAGTTGATA

p.Pro687HisfsTer6

p.P687Hfs*6

Q02156

protein_coding

TCGA-A8-A09C-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PRKCE

insertion

Frame_Shift_Ins

novel

c.460_461insTAACCAACAGACATTCACTTCTCACAGTTTT

p.Arg154IlefsTer131

p.R154Ifs*131

Q02156

protein_coding

TCGA-AN-A03X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PRKCE

insertion

In_Frame_Ins

novel

c.2056_2057insTCTTCATTGGTTCTGCCTCTACTTACACTTTGGAGCTGC

p.Lys686delinsIlePheIleGlySerAlaSerThrTyrThrLeuGluLeuGln

p.K686delinsIFIGSASTYTLELQ

Q02156

protein_coding

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

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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
5581	PRKCE	SERINE THREONINE KINASE, DRUGGABLE GENOME, KINASE, ION CHANNEL, TRANSCRIPTION FACTOR, ENZYME		PHORBOL MYRISTATE ACETATE	PHORBOL MYRISTATE ACETATE	22579485
5581	PRKCE	SERINE THREONINE KINASE, DRUGGABLE GENOME, KINASE, ION CHANNEL, TRANSCRIPTION FACTOR, ENZYME		INGENOL MEBUTATE
5581	PRKCE	SERINE THREONINE KINASE, DRUGGABLE GENOME, KINASE, ION CHANNEL, TRANSCRIPTION FACTOR, ENZYME		[3H]-PHORBOL 12,13-DIBUTYRATE	CHEMBL27768	24794745
5581	PRKCE	SERINE THREONINE KINASE, DRUGGABLE GENOME, KINASE, ION CHANNEL, TRANSCRIPTION FACTOR, ENZYME		KAI-1455
5581	PRKCE	SERINE THREONINE KINASE, DRUGGABLE GENOME, KINASE, ION CHANNEL, TRANSCRIPTION FACTOR, ENZYME	inhibitor	CHEMBL608533	MIDOSTAURIN
5581	PRKCE	SERINE THREONINE KINASE, DRUGGABLE GENOME, KINASE, ION CHANNEL, TRANSCRIPTION FACTOR, ENZYME	inhibitor	249565629	SOTRASTAURIN
5581	PRKCE	SERINE THREONINE KINASE, DRUGGABLE GENOME, KINASE, ION CHANNEL, TRANSCRIPTION FACTOR, ENZYME	inhibitor	178102576	CHELERYTHRINE
5581	PRKCE	SERINE THREONINE KINASE, DRUGGABLE GENOME, KINASE, ION CHANNEL, TRANSCRIPTION FACTOR, ENZYME	inhibitor	CHEMBL3545332	CEP-2563
5581	PRKCE	SERINE THREONINE KINASE, DRUGGABLE GENOME, KINASE, ION CHANNEL, TRANSCRIPTION FACTOR, ENZYME		BRYOSTATIN	BRYOSTATIN
5581	PRKCE	SERINE THREONINE KINASE, DRUGGABLE GENOME, KINASE, ION CHANNEL, TRANSCRIPTION FACTOR, ENZYME		radiotherapy		25054431

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