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: PRKACB

Gene summary for PRKACB

Gene summary.

Gene information	Species	Human
	Gene symbol	PRKACB
	Gene ID	5567
	Gene name	protein kinase cAMP-activated catalytic subunit beta
	Gene Alias	CAFD2
	Cytomap	1p31.1
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	P22694

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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
5567	PRKACB	GSM4909301	Human	Breast	IDC	5.38e-24	5.90e-01	0.1577
5567	PRKACB	M1	Human	Breast	IDC	3.69e-02	1.62e-01	0.1577
5567	PRKACB	NCCBC14	Human	Breast	DCIS	5.45e-05	3.60e-01	0.2021
5567	PRKACB	HTA11_3410_2000001011	Human	Colorectum	AD	2.38e-14	-5.77e-01	0.0155
5567	PRKACB	HTA11_2487_2000001011	Human	Colorectum	SER	1.17e-02	-4.29e-01	-0.1808
5567	PRKACB	HTA11_3361_2000001011	Human	Colorectum	AD	1.42e-04	-5.19e-01	-0.1207
5567	PRKACB	HTA11_696_2000001011	Human	Colorectum	AD	1.79e-04	-3.41e-01	-0.1464
5567	PRKACB	HTA11_866_2000001011	Human	Colorectum	AD	8.70e-03	-3.23e-01	-0.1001
5567	PRKACB	HTA11_1391_2000001011	Human	Colorectum	AD	4.66e-05	-4.40e-01	-0.059
5567	PRKACB	HTA11_866_3004761011	Human	Colorectum	AD	6.29e-08	-4.82e-01	0.096
5567	PRKACB	HTA11_10711_2000001011	Human	Colorectum	AD	9.49e-04	-4.89e-01	0.0338
5567	PRKACB	HTA11_7696_3000711011	Human	Colorectum	AD	2.02e-15	-5.17e-01	0.0674
5567	PRKACB	HTA11_6818_2000001021	Human	Colorectum	AD	2.27e-02	-4.96e-01	0.0588
5567	PRKACB	HTA11_99999970781_79442	Human	Colorectum	MSS	8.53e-13	-4.76e-01	0.294
5567	PRKACB	HTA11_99999965104_69814	Human	Colorectum	MSS	4.35e-02	-4.29e-01	0.281
5567	PRKACB	HTA11_99999971662_82457	Human	Colorectum	MSS	5.30e-22	-6.06e-01	0.3859
5567	PRKACB	HTA11_99999973899_84307	Human	Colorectum	MSS	1.04e-04	-5.89e-01	0.2585
5567	PRKACB	HTA11_99999974143_84620	Human	Colorectum	MSS	4.24e-27	-6.13e-01	0.3005
5567	PRKACB	F007	Human	Colorectum	FAP	1.10e-03	-4.24e-01	0.1176
5567	PRKACB	A001-C-207	Human	Colorectum	FAP	1.12e-02	-2.87e-01	0.1278

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
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
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:005087813	Breast	IDC	regulation of body fluid levels	50/1434	379/18723	1.12e-04	2.10e-03	50
GO:006056212	Breast	IDC	epithelial tube morphogenesis	44/1434	325/18723	1.58e-04	2.73e-03	44
GO:003514812	Breast	IDC	tube formation	23/1434	148/18723	8.79e-04	1.02e-02	23
GO:000183812	Breast	IDC	embryonic epithelial tube formation	19/1434	121/18723	2.10e-03	1.97e-02	19
GO:00721756	Breast	IDC	epithelial tube formation	19/1434	132/18723	5.63e-03	4.08e-02	19
GO:005160413	Breast	IDC	protein maturation	35/1434	294/18723	6.18e-03	4.40e-02	35
GO:005087823	Breast	DCIS	regulation of body fluid levels	50/1390	379/18723	5.17e-05	1.06e-03	50
GO:006056221	Breast	DCIS	epithelial tube morphogenesis	41/1390	325/18723	5.98e-04	7.60e-03	41
GO:003514821	Breast	DCIS	tube formation	21/1390	148/18723	3.08e-03	2.62e-02	21
GO:000183821	Breast	DCIS	embryonic epithelial tube formation	18/1390	121/18723	3.54e-03	2.92e-02	18
GO:005160422	Breast	DCIS	protein maturation	34/1390	294/18723	6.72e-03	4.66e-02	34
GO:00030144	Breast	DCIS	renal system process	16/1390	110/18723	7.16e-03	4.85e-02	16
GO:0050878	Colorectum	AD	regulation of body fluid levels	108/3918	379/18723	2.54e-04	3.20e-03	108
GO:0060562	Colorectum	AD	epithelial tube morphogenesis	93/3918	325/18723	5.65e-04	6.00e-03	93
GO:0051604	Colorectum	AD	protein maturation	85/3918	294/18723	6.73e-04	6.91e-03	85
GO:0014020	Colorectum	AD	primary neural tube formation	33/3918	94/18723	1.02e-03	9.50e-03	33
GO:0001841	Colorectum	AD	neural tube formation	35/3918	102/18723	1.16e-03	1.05e-02	35
GO:0001843	Colorectum	AD	neural tube closure	30/3918	88/18723	2.83e-03	2.12e-02	30
GO:0060606	Colorectum	AD	tube closure	30/3918	89/18723	3.42e-03	2.49e-02	30
GO:0035148	Colorectum	AD	tube formation	45/3918	148/18723	4.13e-03	2.87e-02	45

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0491925	Prostate	Tumor	Thyroid hormone signaling pathway	40/1791	121/8465	1.47e-03	6.26e-03	3.88e-03	40
hsa0491022	Prostate	Tumor	Insulin signaling pathway	44/1791	137/8465	1.69e-03	7.10e-03	4.40e-03	44
hsa0496221	Prostate	Tumor	Vasopressin-regulated water reabsorption	18/1791	44/8465	2.31e-03	8.85e-03	5.49e-03	18
hsa0503121	Prostate	Tumor	Amphetamine addiction	25/1791	69/8465	2.78e-03	1.05e-02	6.48e-03	25
hsa0492822	Prostate	Tumor	Parathyroid hormone synthesis, secretion and action	35/1791	106/8465	2.89e-03	1.07e-02	6.67e-03	35
hsa0414023	Prostate	Tumor	Autophagy - animal	44/1791	141/8465	3.16e-03	1.15e-02	7.12e-03	44
hsa0431023	Prostate	Tumor	Wnt signaling pathway	50/1791	171/8465	7.32e-03	2.37e-02	1.47e-02	50
hsa0501237	Prostate	Tumor	Parkinson disease	144/1791	266/8465	3.33e-33	1.10e-30	6.83e-31	144
hsa0502036	Prostate	Tumor	Prion disease	142/1791	273/8465	2.80e-30	3.09e-28	1.92e-28	142
hsa0471437	Prostate	Tumor	Thermogenesis	110/1791	232/8465	1.56e-19	3.96e-18	2.46e-18	110
hsa0453037	Prostate	Tumor	Tight junction	69/1791	169/8465	3.92e-09	6.18e-08	3.83e-08	69
hsa0516532	Prostate	Tumor	Human papillomavirus infection	110/1791	331/8465	1.31e-07	1.51e-06	9.36e-07	110
hsa0516637	Prostate	Tumor	Human T-cell leukemia virus 1 infection	78/1791	222/8465	7.99e-07	8.02e-06	4.97e-06	78
hsa0520535	Prostate	Tumor	Proteoglycans in cancer	73/1791	205/8465	1.01e-06	9.82e-06	6.09e-06	73
hsa0520333	Prostate	Tumor	Viral carcinogenesis	70/1791	204/8465	7.53e-06	6.56e-05	4.07e-05	70
hsa0511035	Prostate	Tumor	Vibrio cholerae infection	24/1791	50/8465	2.10e-05	1.70e-04	1.05e-04	24
hsa0516336	Prostate	Tumor	Human cytomegalovirus infection	74/1791	225/8465	2.27e-05	1.79e-04	1.11e-04	74
hsa0472335	Prostate	Tumor	Retrograde endocannabinoid signaling	51/1791	148/8465	1.12e-04	7.25e-04	4.49e-04	51
hsa0152231	Prostate	Tumor	Endocrine resistance	37/1791	98/8465	1.17e-04	7.42e-04	4.60e-04	37
hsa0491536	Prostate	Tumor	Estrogen signaling pathway	48/1791	138/8465	1.36e-04	8.33e-04	5.17e-04	48

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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

PRKACB

SNV

Missense_Mutation

novel

c.658C>A

p.Leu220Ile

p.L220I

P22694

protein_coding

tolerated(0.43)

benign(0.089)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PRKACB

SNV

Missense_Mutation

c.732N>T

p.Trp244Cys

p.W244C

P22694

protein_coding

deleterious(0)

benign(0.102)

TCGA-AA-3815-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

PRKACB

SNV

Missense_Mutation

c.1022N>A

p.Thr341Asn

p.T341N

P22694

protein_coding

tolerated(1)

benign(0)

TCGA-CM-4748-01

Colorectum

colon adenocarcinoma

Male

<65

III/IV

Chemotherapy

fluorouracil

PRKACB

SNV

Missense_Mutation

novel

c.260N>A

p.Gly87Glu

p.G87E

P22694

protein_coding

tolerated(0.27)

benign(0.003)

TCGA-AJ-A5DW-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

PRKACB

SNV

Missense_Mutation

c.515C>A

p.Pro172His

p.P172H

P22694

protein_coding

tolerated(0.11)

possibly_damaging(0.833)

TCGA-AP-A051-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

PRKACB

SNV

Missense_Mutation

novel

c.565N>A

p.Pro189Thr

p.P189T

P22694

protein_coding

deleterious(0.05)

benign(0.066)

TCGA-AP-A059-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

PRKACB

SNV

Missense_Mutation

rs148797911

c.259N>A

p.Gly87Arg

p.G87R

P22694

protein_coding

tolerated(0.13)

benign(0.005)

TCGA-AP-A1DV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

PRKACB

SNV

Missense_Mutation

novel

c.574C>T

p.Arg192Trp

p.R192W

P22694

protein_coding

deleterious(0.02)

probably_damaging(0.997)

TCGA-AX-A1CE-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

PRKACB

SNV

Missense_Mutation

novel

c.68A>G

p.Glu23Gly

p.E23G

P22694

protein_coding

tolerated_low_confidence(0.06)

benign(0.223)

TCGA-AX-A2HD-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Unknown

PRKACB

SNV

Missense_Mutation

c.341A>C

p.Glu114Ala

p.E114A

P22694

protein_coding

tolerated(0.27)

benign(0.015)

TCGA-B5-A0JY-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

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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
5567	PRKACB	ENZYME, KINASE, CLINICALLY ACTIONABLE, G PROTEIN COUPLED RECEPTOR, DRUGGABLE GENOME, SERINE THREONINE KINASE	inhibitor	178101884	GSK-690693
5567	PRKACB	ENZYME, KINASE, CLINICALLY ACTIONABLE, G PROTEIN COUPLED RECEPTOR, DRUGGABLE GENOME, SERINE THREONINE KINASE		FASUDIL	FASUDIL	22257127
5567	PRKACB	ENZYME, KINASE, CLINICALLY ACTIONABLE, G PROTEIN COUPLED RECEPTOR, DRUGGABLE GENOME, SERINE THREONINE KINASE	inhibitor	135652717	STAUROSPORINE
5567	PRKACB	ENZYME, KINASE, CLINICALLY ACTIONABLE, G PROTEIN COUPLED RECEPTOR, DRUGGABLE GENOME, SERINE THREONINE KINASE	inhibitor	CHEMBL494089	GSK-690693

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