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: PRKCH

Gene summary for PRKCH

Gene summary.

Gene information	Species	Human
	Gene symbol	PRKCH
	Gene ID	5583
	Gene name	protein kinase C eta
	Gene Alias	PKC-L
	Cytomap	14q23.1
	Gene Type	protein-coding
	GO ID	GO:0002253
	UniProtAcc	P24723

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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
5583	PRKCH	CCI_1	Human	Cervix	CC	1.51e-21	1.06e+00	0.528
5583	PRKCH	CCI_2	Human	Cervix	CC	2.05e-17	1.52e+00	0.5249
5583	PRKCH	CCI_3	Human	Cervix	CC	5.19e-22	8.49e-01	0.516
5583	PRKCH	sample3	Human	Cervix	CC	1.59e-07	1.60e-01	0.1387
5583	PRKCH	AEH-subject1	Human	Endometrium	AEH	7.18e-18	4.42e-01	-0.3059
5583	PRKCH	AEH-subject2	Human	Endometrium	AEH	8.46e-10	3.60e-01	-0.2525
5583	PRKCH	AEH-subject3	Human	Endometrium	AEH	1.03e-04	2.83e-01	-0.2576
5583	PRKCH	AEH-subject4	Human	Endometrium	AEH	9.73e-17	5.34e-01	-0.2657
5583	PRKCH	AEH-subject5	Human	Endometrium	AEH	1.82e-28	6.65e-01	-0.2953
5583	PRKCH	EEC-subject1	Human	Endometrium	EEC	1.04e-02	2.78e-01	-0.2682
5583	PRKCH	EEC-subject2	Human	Endometrium	EEC	2.73e-08	3.46e-01	-0.2607
5583	PRKCH	EEC-subject4	Human	Endometrium	EEC	4.06e-18	5.31e-01	-0.2571
5583	PRKCH	EEC-subject5	Human	Endometrium	EEC	4.57e-16	4.88e-01	-0.249
5583	PRKCH	LZE4T	Human	Esophagus	ESCC	7.68e-07	2.14e-01	0.0811
5583	PRKCH	LZE7T	Human	Esophagus	ESCC	5.98e-07	3.91e-01	0.0667
5583	PRKCH	LZE8T	Human	Esophagus	ESCC	1.57e-02	1.05e-01	0.067
5583	PRKCH	LZE20T	Human	Esophagus	ESCC	4.19e-08	2.57e-01	0.0662
5583	PRKCH	LZE22T	Human	Esophagus	ESCC	1.07e-04	5.00e-01	0.068
5583	PRKCH	LZE24T	Human	Esophagus	ESCC	2.47e-17	2.70e-01	0.0596
5583	PRKCH	LZE6T	Human	Esophagus	ESCC	1.39e-04	2.55e-01	0.0845

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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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
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

∗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:00302166	Oral cavity	OSCC	keratinocyte differentiation	81/7305	139/18723	3.16e-06	3.81e-05	81
GO:00507696	Oral cavity	OSCC	positive regulation of neurogenesis	120/7305	225/18723	8.45e-06	9.02e-05	120
GO:00099139	Oral cavity	OSCC	epidermal cell differentiation	109/7305	202/18723	1.08e-05	1.14e-04	109
GO:00420635	Oral cavity	OSCC	gliogenesis	154/7305	301/18723	1.10e-05	1.14e-04	154
GO:00510917	Oral cavity	OSCC	positive regulation of DNA-binding transcription factor activity	134/7305	260/18723	2.52e-05	2.35e-04	134
GO:0034350	Oral cavity	OSCC	regulation of glial cell apoptotic process	11/7305	11/18723	3.17e-05	2.87e-04	11
GO:00507679	Oral cavity	OSCC	regulation of neurogenesis	179/7305	364/18723	4.49e-05	3.84e-04	179
GO:0014009	Oral cavity	OSCC	glial cell proliferation	34/7305	51/18723	5.83e-05	4.80e-04	34
GO:00456825	Oral cavity	OSCC	regulation of epidermis development	41/7305	65/18723	7.29e-05	5.73e-04	41
GO:190437716	Oral cavity	OSCC	positive regulation of protein localization to cell periphery	43/7305	69/18723	7.43e-05	5.81e-04	43
GO:190307815	Oral cavity	OSCC	positive regulation of protein localization to plasma membrane	39/7305	62/18723	1.19e-04	8.54e-04	39
GO:00510925	Oral cavity	OSCC	positive regulation of NF-kappaB transcription factor activity	82/7305	152/18723	1.28e-04	9.13e-04	82
GO:00519624	Oral cavity	OSCC	positive regulation of nervous system development	135/7305	272/18723	2.20e-04	1.44e-03	135
GO:00456045	Oral cavity	OSCC	regulation of epidermal cell differentiation	36/7305	58/18723	3.15e-04	1.96e-03	36
GO:0014015	Oral cavity	OSCC	positive regulation of gliogenesis	39/7305	66/18723	7.46e-04	4.07e-03	39
GO:00519605	Oral cavity	OSCC	regulation of nervous system development	205/7305	443/18723	9.80e-04	5.11e-03	205
GO:0060251	Oral cavity	OSCC	regulation of glial cell proliferation	23/7305	36/18723	2.19e-03	9.95e-03	23
GO:00027646	Oral cavity	OSCC	immune response-regulating signaling pathway	212/7305	468/18723	2.93e-03	1.27e-02	212
GO:00456166	Oral cavity	OSCC	regulation of keratinocyte differentiation	23/7305	37/18723	3.66e-03	1.51e-02	23
GO:004521618	Oral cavity	OSCC	cell-cell junction organization	97/7305	200/18723	3.83e-03	1.57e-02	97

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa042704	Oral cavity	NEOLP	Vascular smooth muscle contraction	30/1112	134/8465	2.06e-03	8.97e-03	5.64e-03	30
hsa0427011	Oral cavity	NEOLP	Vascular smooth muscle contraction	30/1112	134/8465	2.06e-03	8.97e-03	5.64e-03	30

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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

PRKCH

SNV

Missense_Mutation

novel

c.1532N>A

p.Thr511Lys

p.T511K

P24723

protein_coding

deleterious(0)

probably_damaging(0.984)

TCGA-A2-A1G1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PRKCH

SNV

Missense_Mutation

novel

c.208N>A

p.Glu70Lys

p.E70K

P24723

protein_coding

tolerated(0.06)

probably_damaging(0.941)

TCGA-AR-A2LE-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

PRKCH

SNV

Missense_Mutation

c.1771N>G

p.Lys591Glu

p.K591E

P24723

protein_coding

deleterious(0)

probably_damaging(0.974)

TCGA-BH-A0BZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

PRKCH

SNV

Missense_Mutation

novel

c.1511G>C

p.Gly504Ala

p.G504A

P24723

protein_coding

deleterious(0)

possibly_damaging(0.607)

TCGA-BH-A0DS-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

cyclophosphamide

PRKCH

SNV

Missense_Mutation

c.291N>A

p.Phe97Leu

p.F97L

P24723

protein_coding

tolerated(0.12)

probably_damaging(1)

TCGA-E2-A152-01

Breast

breast invasive carcinoma

Female

<65

I/II

Targeted Molecular therapy

trastuzumab

PRKCH

SNV

Missense_Mutation

novel

c.1738G>T

p.Asp580Tyr

p.D580Y

P24723

protein_coding

deleterious(0)

probably_damaging(0.969)

TCGA-E9-A1N9-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

PRKCH

insertion

Frame_Shift_Ins

novel

c.1247_1248insAAACCCAGGATCCTGGGTTATGCTTTTGTCTGGGGACCAGGCAGGA

p.Thr417AsnfsTer39

p.T417Nfs*39

P24723

protein_coding

TCGA-BH-A0B1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

adriamycin

PRKCH

insertion

Nonsense_Mutation

novel

c.1982_1983insGCTCCAGCCTGGGCAACTGAGTTAGACTTTGTCTCAAAAA

p.His662LeufsTer8

p.H662Lfs*8

P24723

protein_coding

TCGA-BH-A0HW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

PRKCH

SNV

Missense_Mutation

c.291N>G

p.Phe97Leu

p.F97L

P24723

protein_coding

tolerated(0.12)

probably_damaging(1)

TCGA-C5-A1BQ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

PRKCH

SNV

Missense_Mutation

novel

c.671N>A

p.Cys224Tyr

p.C224Y

P24723

protein_coding

tolerated(0.19)

possibly_damaging(0.793)

TCGA-MY-A5BF-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

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
5583	PRKCH	ENZYME, KINASE, DRUGGABLE GENOME, SERINE THREONINE KINASE	inhibitor	249565629	SOTRASTAURIN
5583	PRKCH	ENZYME, KINASE, DRUGGABLE GENOME, SERINE THREONINE KINASE	inhibitor	CHEMBL3545332	CEP-2563
5583	PRKCH	ENZYME, KINASE, DRUGGABLE GENOME, SERINE THREONINE KINASE		BRYOSTATIN-1
5583	PRKCH	ENZYME, KINASE, DRUGGABLE GENOME, SERINE THREONINE KINASE		BRYOSTATIN	BRYOSTATIN
5583	PRKCH	ENZYME, KINASE, DRUGGABLE GENOME, SERINE THREONINE KINASE	inhibitor	CHEMBL494089	GSK-690693
5583	PRKCH	ENZYME, KINASE, DRUGGABLE GENOME, SERINE THREONINE KINASE	inhibitor	CHEMBL565612	SOTRASTAURIN
5583	PRKCH	ENZYME, KINASE, DRUGGABLE GENOME, SERINE THREONINE KINASE		INGENOL MEBUTATE
5583	PRKCH	ENZYME, KINASE, DRUGGABLE GENOME, SERINE THREONINE KINASE	inhibitor	CHEMBL608533	MIDOSTAURIN
5583	PRKCH	ENZYME, KINASE, DRUGGABLE GENOME, SERINE THREONINE KINASE	inhibitor	249565822	BALANOL
5583	PRKCH	ENZYME, KINASE, DRUGGABLE GENOME, SERINE THREONINE KINASE	inhibitor	SOPHORETIN	QUERCETIN

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