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:00085446	Cervix	CC	epidermis development	83/2311	324/18723	3.91e-11	8.54e-09	83
GO:00435884	Cervix	CC	skin development	71/2311	263/18723	8.04e-11	1.46e-08	71
GO:190382910	Cervix	CC	positive regulation of cellular protein localization	72/2311	276/18723	3.20e-10	4.46e-08	72
GO:007265910	Cervix	CC	protein localization to plasma membrane	73/2311	284/18723	4.95e-10	6.73e-08	73
GO:19907788	Cervix	CC	protein localization to cell periphery	78/2311	333/18723	1.22e-08	9.73e-07	78
GO:00302164	Cervix	CC	keratinocyte differentiation	42/2311	139/18723	1.74e-08	1.28e-06	42
GO:00452169	Cervix	CC	cell-cell junction organization	53/2311	200/18723	3.83e-08	2.53e-06	53
GO:00099137	Cervix	CC	epidermal cell differentiation	53/2311	202/18723	5.48e-08	3.25e-06	53
GO:00027644	Cervix	CC	immune response-regulating signaling pathway	97/2311	468/18723	1.49e-07	7.07e-06	97
GO:00343298	Cervix	CC	cell junction assembly	88/2311	420/18723	3.42e-07	1.38e-05	88
GO:19043779	Cervix	CC	positive regulation of protein localization to cell periphery	24/2311	69/18723	1.21e-06	4.15e-05	24
GO:00070439	Cervix	CC	cell-cell junction assembly	39/2311	146/18723	1.86e-06	5.94e-05	39
GO:00510904	Cervix	CC	regulation of DNA-binding transcription factor activity	87/2311	440/18723	4.85e-06	1.22e-04	87
GO:00456822	Cervix	CC	regulation of epidermis development	22/2311	65/18723	5.56e-06	1.38e-04	22
GO:00107206	Cervix	CC	positive regulation of cell development	64/2311	298/18723	5.69e-06	1.41e-04	64
GO:19030788	Cervix	CC	positive regulation of protein localization to plasma membrane	21/2311	62/18723	8.91e-06	2.03e-04	21
GO:00456042	Cervix	CC	regulation of epidermal cell differentiation	20/2311	58/18723	1.07e-05	2.33e-04	20
GO:00432978	Cervix	CC	apical junction assembly	24/2311	78/18723	1.36e-05	2.73e-04	24
GO:19054778	Cervix	CC	positive regulation of protein localization to membrane	29/2311	106/18723	2.29e-05	4.01e-04	29
GO:00181057	Cervix	CC	peptidyl-serine phosphorylation	63/2311	315/18723	6.65e-05	9.47e-04	63

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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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