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: PRKCB

Gene summary for PRKCB

Gene summary.

Gene information	Species	Human
	Gene symbol	PRKCB
	Gene ID	5579
	Gene name	protein kinase C beta
	Gene Alias	PKC-beta
	Cytomap	16p12.2-p12.1
	Gene Type	protein-coding
	GO ID	GO:0000278
	UniProtAcc	P05771

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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
5579	PRKCB	EOLP-1	Human	Oral cavity	EOLP	1.20e-22	7.29e-01	-0.0202
5579	PRKCB	EOLP-2	Human	Oral cavity	EOLP	5.10e-13	5.17e-01	-0.0203
5579	PRKCB	NEOLP-3	Human	Oral cavity	NEOLP	1.37e-02	1.88e-01	-0.0191

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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:001810514	Oral cavity	EOLP	peptidyl-serine phosphorylation	84/2218	315/18723	3.32e-13	1.05e-10	84
GO:001820914	Oral cavity	EOLP	peptidyl-serine modification	87/2218	338/18723	1.07e-12	2.46e-10	87
GO:000276413	Oral cavity	EOLP	immune response-regulating signaling pathway	108/2218	468/18723	4.04e-12	7.34e-10	108
GO:190165323	Oral cavity	EOLP	cellular response to peptide	85/2218	359/18723	2.06e-10	2.06e-08	85
GO:001657023	Oral cavity	EOLP	histone modification	98/2218	463/18723	5.58e-09	2.96e-07	98
GO:002241121	Oral cavity	EOLP	cellular component disassembly	94/2218	443/18723	1.00e-08	4.89e-07	94
GO:004343424	Oral cavity	EOLP	response to peptide hormone	89/2218	414/18723	1.29e-08	6.11e-07	89
GO:003286922	Oral cavity	EOLP	cellular response to insulin stimulus	53/2218	203/18723	1.65e-08	7.43e-07	53
GO:007137523	Oral cavity	EOLP	cellular response to peptide hormone stimulus	68/2218	290/18723	1.98e-08	8.62e-07	68
GO:003286823	Oral cavity	EOLP	response to insulin	62/2218	264/18723	7.78e-08	2.76e-06	62
GO:004312223	Oral cavity	EOLP	regulation of I-kappaB kinase/NF-kappaB signaling	58/2218	249/18723	2.72e-07	8.22e-06	58
GO:001821015	Oral cavity	EOLP	peptidyl-threonine modification	35/2218	125/18723	7.33e-07	1.85e-05	35
GO:000724924	Oral cavity	EOLP	I-kappaB kinase/NF-kappaB signaling	62/2218	281/18723	8.00e-07	2.02e-05	62
GO:001810715	Oral cavity	EOLP	peptidyl-threonine phosphorylation	33/2218	116/18723	1.02e-06	2.51e-05	33
GO:00027683	Oral cavity	EOLP	immune response-regulating cell surface receptor signaling pathway	66/2218	315/18723	2.44e-06	5.45e-05	66
GO:000828615	Oral cavity	EOLP	insulin receptor signaling pathway	32/2218	116/18723	3.06e-06	6.70e-05	32
GO:00510811	Oral cavity	EOLP	nuclear envelope disassembly	8/2218	11/18723	4.54e-06	9.41e-05	8
GO:00024292	Oral cavity	EOLP	immune response-activating cell surface receptor signaling pathway	60/2218	291/18723	1.16e-05	2.00e-04	60
GO:00027572	Oral cavity	EOLP	immune response-activating signal transduction	60/2218	291/18723	1.16e-05	2.00e-04	60
GO:00303971	Oral cavity	EOLP	membrane disassembly	8/2218	12/18723	1.22e-05	2.09e-04	8

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0517146	Oral cavity	EOLP	Coronavirus disease - COVID-19	108/1218	232/8465	8.08e-33	2.61e-30	1.54e-30	108
hsa0516442	Oral cavity	EOLP	Influenza A	58/1218	171/8465	7.01e-11	3.23e-09	1.91e-09	58
hsa0541545	Oral cavity	EOLP	Diabetic cardiomyopathy	64/1218	203/8465	2.48e-10	1.00e-08	5.91e-09	64
hsa0516345	Oral cavity	EOLP	Human cytomegalovirus infection	68/1218	225/8465	5.29e-10	1.90e-08	1.12e-08	68
hsa0407141	Oral cavity	EOLP	Sphingolipid signaling pathway	44/1218	121/8465	1.19e-09	3.51e-08	2.07e-08	44
hsa0517043	Oral cavity	EOLP	Human immunodeficiency virus 1 infection	63/1218	212/8465	4.85e-09	8.71e-08	5.14e-08	63
hsa0451026	Oral cavity	EOLP	Focal adhesion	60/1218	203/8465	1.42e-08	1.83e-07	1.08e-07	60
hsa0502245	Oral cavity	EOLP	Pathways of neurodegeneration - multiple diseases	110/1218	476/8465	1.09e-07	1.26e-06	7.40e-07	110
hsa0516141	Oral cavity	EOLP	Hepatitis B	49/1218	162/8465	1.38e-07	1.54e-06	9.07e-07	49
hsa04670210	Oral cavity	EOLP	Leukocyte transendothelial migration	37/1218	114/8465	7.00e-07	6.85e-06	4.04e-06	37
hsa046622	Oral cavity	EOLP	B cell receptor signaling pathway	29/1218	84/8465	2.75e-06	2.11e-05	1.25e-05	29
hsa0466623	Oral cavity	EOLP	Fc gamma R-mediated phagocytosis	31/1218	97/8465	7.90e-06	4.73e-05	2.79e-05	31
hsa0520543	Oral cavity	EOLP	Proteoglycans in cancer	53/1218	205/8465	9.07e-06	5.33e-05	3.14e-05	53
hsa04650	Oral cavity	EOLP	Natural killer cell mediated cytotoxicity	38/1218	132/8465	1.26e-05	7.01e-05	4.13e-05	38
hsa0406643	Oral cavity	EOLP	HIF-1 signaling pathway	33/1218	109/8465	1.48e-05	8.08e-05	4.76e-05	33
hsa0401223	Oral cavity	EOLP	ErbB signaling pathway	27/1218	85/8465	3.39e-05	1.69e-04	9.94e-05	27
hsa040642	Oral cavity	EOLP	NF-kappa B signaling pathway	31/1218	104/8465	3.72e-05	1.82e-04	1.07e-04	31
hsa0152124	Oral cavity	EOLP	EGFR tyrosine kinase inhibitor resistance	25/1218	79/8465	7.03e-05	3.25e-04	1.91e-04	25
hsa0401023	Oral cavity	EOLP	MAPK signaling pathway	68/1218	302/8465	7.48e-05	3.40e-04	2.01e-04	68
hsa0521424	Oral cavity	EOLP	Glioma	24/1218	75/8465	8.01e-05	3.59e-04	2.12e-04	24

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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

PRKCB

SNV

Missense_Mutation

rs767640161

c.1774N>T

p.Arg592Cys

p.R592C

P05771

protein_coding

deleterious(0.01)

possibly_damaging(0.877)

TCGA-A8-A091-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

PRKCB

SNV

Missense_Mutation

c.927N>C

p.Lys309Asn

p.K309N

P05771

protein_coding

tolerated(0.14)

benign(0.013)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PRKCB

SNV

Missense_Mutation

c.1834N>C

p.Glu612Gln

p.E612Q

P05771

protein_coding

tolerated(0.18)

benign(0.287)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PRKCB

SNV

Missense_Mutation

novel

c.371N>C

p.Gly124Ala

p.G124A

P05771

protein_coding

deleterious(0)

probably_damaging(0.98)

TCGA-AC-A6IW-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PRKCB

SNV

Missense_Mutation

rs747105951

c.586N>A

p.Val196Ile

p.V196I

P05771

protein_coding

tolerated(0.07)

benign(0.345)

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

PRKCB

SNV

Missense_Mutation

c.1007G>A

p.Arg336Gln

p.R336Q

P05771

protein_coding

tolerated(0.14)

benign(0.003)

TCGA-AR-A1AW-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

docetaxel

PRKCB

SNV

Missense_Mutation

c.1526N>T

p.Ala509Val

p.A509V

P05771

protein_coding

deleterious(0.02)

probably_damaging(0.999)

TCGA-BH-A0HB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

docetaxel

PRKCB

SNV

Missense_Mutation

rs775118763

c.2008N>A

p.Glu670Lys

p.E670K

P05771

protein_coding

tolerated_low_confidence(0.63)

benign(0.157)

TCGA-BH-A5J0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PRKCB

SNV

Missense_Mutation

c.1093G>A

p.Asp365Asn

p.D365N

P05771

protein_coding

deleterious(0.01)

benign(0.067)

TCGA-D8-A1JN-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozolum

PRKCB

SNV

Missense_Mutation

c.827N>T

p.Lys276Met

p.K276M

P05771

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-E9-A1RF-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

tamoxiphen

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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
5579	PRKCB	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYME, CLINICALLY ACTIONABLE, TRANSPORTER		BRYOSTATIN	BRYOSTATIN
5579	PRKCB	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYME, CLINICALLY ACTIONABLE, TRANSPORTER	inhibitor	178102647
5579	PRKCB	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYME, CLINICALLY ACTIONABLE, TRANSPORTER		atenolol	ATENOLOL
5579	PRKCB	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYME, CLINICALLY ACTIONABLE, TRANSPORTER		Sotrastaurin acetate
5579	PRKCB	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYME, CLINICALLY ACTIONABLE, TRANSPORTER		BISINDOLYLMALEIMIDE IX	BISINDOLYLMALEIMIDE IX	25058929
5579	PRKCB	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYME, CLINICALLY ACTIONABLE, TRANSPORTER	inhibitor	249565629	SOTRASTAURIN
5579	PRKCB	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYME, CLINICALLY ACTIONABLE, TRANSPORTER		dexmedetomidine	DEXMEDETOMIDINE
5579	PRKCB	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYME, CLINICALLY ACTIONABLE, TRANSPORTER		INGENOL MEBUTATE
5579	PRKCB	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYME, CLINICALLY ACTIONABLE, TRANSPORTER	inhibitor	178101880
5579	PRKCB	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYME, CLINICALLY ACTIONABLE, TRANSPORTER	inhibitor	CHEMBL494089	GSK-690693

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