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: PRKDC

Gene summary for PRKDC

Gene summary.

Gene information	Species	Human
	Gene symbol	PRKDC
	Gene ID	5591
	Gene name	protein kinase, DNA-activated, catalytic subunit
	Gene Alias	DNA-PKC
	Cytomap	8q11.21
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	P78527

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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
5591	PRKDC	GSM4909281	Human	Breast	IDC	9.06e-13	3.90e-01	0.21
5591	PRKDC	GSM4909282	Human	Breast	IDC	9.19e-13	3.20e-01	-0.0288
5591	PRKDC	GSM4909285	Human	Breast	IDC	2.06e-08	2.47e-01	0.21
5591	PRKDC	GSM4909287	Human	Breast	IDC	5.12e-06	3.20e-01	0.2057
5591	PRKDC	GSM4909291	Human	Breast	IDC	6.44e-05	3.39e-01	0.1753
5591	PRKDC	GSM4909293	Human	Breast	IDC	1.36e-51	7.30e-01	0.1581
5591	PRKDC	GSM4909301	Human	Breast	IDC	1.79e-06	2.61e-01	0.1577
5591	PRKDC	GSM4909304	Human	Breast	IDC	1.33e-30	5.56e-01	0.1636
5591	PRKDC	GSM4909306	Human	Breast	IDC	3.46e-09	3.13e-01	0.1564
5591	PRKDC	GSM4909307	Human	Breast	IDC	3.54e-02	1.48e-01	0.1569
5591	PRKDC	GSM4909311	Human	Breast	IDC	1.44e-05	-5.70e-02	0.1534
5591	PRKDC	GSM4909317	Human	Breast	IDC	2.66e-24	6.06e-01	0.1355
5591	PRKDC	GSM4909319	Human	Breast	IDC	1.92e-08	-6.15e-02	0.1563
5591	PRKDC	GSM4909321	Human	Breast	IDC	4.89e-02	1.72e-03	0.1559
5591	PRKDC	brca2	Human	Breast	Precancer	6.07e-07	9.07e-02	-0.024
5591	PRKDC	M1	Human	Breast	IDC	9.38e-12	4.79e-01	0.1577
5591	PRKDC	NCCBC2	Human	Breast	DCIS	2.32e-05	4.21e-01	0.1554
5591	PRKDC	NCCBC3	Human	Breast	DCIS	3.68e-09	3.35e-01	0.1198
5591	PRKDC	P1	Human	Breast	IDC	9.14e-05	6.90e-02	0.1527
5591	PRKDC	P2	Human	Breast	IDC	4.83e-09	4.94e-01	0.21

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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
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
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
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ
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:004227418	Prostate	BPH	ribosomal small subunit biogenesis	25/3107	73/18723	1.82e-04	1.53e-03	25
GO:000931414	Prostate	BPH	response to radiation	105/3107	456/18723	2.07e-04	1.70e-03	105
GO:00457863	Prostate	BPH	negative regulation of cell cycle	91/3107	385/18723	2.10e-04	1.71e-03	91
GO:004211010	Prostate	BPH	T cell activation	111/3107	487/18723	2.11e-04	1.72e-03	111
GO:00102127	Prostate	BPH	response to ionizing radiation	42/3107	148/18723	2.20e-04	1.78e-03	42
GO:20007363	Prostate	BPH	regulation of stem cell differentiation	21/3107	58/18723	2.44e-04	1.94e-03	21
GO:00026839	Prostate	BPH	negative regulation of immune system process	100/3107	434/18723	2.83e-04	2.20e-03	100
GO:00459303	Prostate	BPH	negative regulation of mitotic cell cycle	60/3107	235/18723	3.00e-04	2.32e-03	60
GO:00022444	Prostate	BPH	hematopoietic progenitor cell differentiation	34/3107	114/18723	3.08e-04	2.37e-03	34
GO:19031315	Prostate	BPH	mononuclear cell differentiation	98/3107	426/18723	3.43e-04	2.55e-03	98
GO:00903982	Prostate	BPH	cellular senescence	29/3107	93/18723	3.66e-04	2.71e-03	29
GO:00103325	Prostate	BPH	response to gamma radiation	20/3107	56/18723	4.19e-04	3.02e-03	20
GO:00315716	Prostate	BPH	mitotic G1 DNA damage checkpoint	13/3107	30/18723	5.11e-04	3.62e-03	13
GO:19020362	Prostate	BPH	regulation of hematopoietic stem cell differentiation	8/3107	14/18723	6.63e-04	4.46e-03	8
GO:00448196	Prostate	BPH	mitotic G1/S transition checkpoint	13/3107	31/18723	7.48e-04	4.95e-03	13
GO:00330023	Prostate	BPH	muscle cell proliferation	61/3107	248/18723	7.61e-04	5.02e-03	61
GO:00486605	Prostate	BPH	regulation of smooth muscle cell proliferation	47/3107	180/18723	7.63e-04	5.03e-03	47
GO:19019874	Prostate	BPH	regulation of cell cycle phase transition	89/3107	390/18723	8.17e-04	5.34e-03	89
GO:19028072	Prostate	BPH	negative regulation of cell cycle G1/S phase transition	28/3107	93/18723	8.54e-04	5.53e-03	28
GO:19019913	Prostate	BPH	negative regulation of mitotic cell cycle phase transition	46/3107	179/18723	1.24e-03	7.51e-03	46

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa041106	Cervix	CC	Cell cycle	36/1267	157/8465	4.94e-03	1.67e-02	9.86e-03	36
hsa0411013	Cervix	CC	Cell cycle	36/1267	157/8465	4.94e-03	1.67e-02	9.86e-03	36
hsa041109	Esophagus	HGIN	Cell cycle	38/1383	157/8465	6.70e-03	4.37e-02	3.47e-02	38
hsa0411016	Esophagus	HGIN	Cell cycle	38/1383	157/8465	6.70e-03	4.37e-02	3.47e-02	38
hsa0411023	Esophagus	ESCC	Cell cycle	126/4205	157/8465	1.34e-15	5.60e-14	2.87e-14	126
hsa0411033	Esophagus	ESCC	Cell cycle	126/4205	157/8465	1.34e-15	5.60e-14	2.87e-14	126
hsa041104	Liver	Cirrhotic	Cell cycle	61/2530	157/8465	9.53e-03	3.21e-02	1.98e-02	61
hsa0411011	Liver	Cirrhotic	Cell cycle	61/2530	157/8465	9.53e-03	3.21e-02	1.98e-02	61
hsa041102	Liver	HCC	Cell cycle	106/4020	157/8465	2.54e-07	3.04e-06	1.69e-06	106
hsa041103	Liver	HCC	Cell cycle	106/4020	157/8465	2.54e-07	3.04e-06	1.69e-06	106
hsa041105	Lung	IAC	Cell cycle	30/1053	157/8465	1.03e-02	3.83e-02	2.54e-02	30
hsa0411012	Lung	IAC	Cell cycle	30/1053	157/8465	1.03e-02	3.83e-02	2.54e-02	30
hsa041108	Oral cavity	OSCC	Cell cycle	118/3704	157/8465	7.15e-16	2.66e-14	1.35e-14	118
hsa0411015	Oral cavity	OSCC	Cell cycle	118/3704	157/8465	7.15e-16	2.66e-14	1.35e-14	118
hsa0411022	Oral cavity	LP	Cell cycle	70/2418	157/8465	1.17e-05	8.27e-05	5.33e-05	70
hsa0411032	Oral cavity	LP	Cell cycle	70/2418	157/8465	1.17e-05	8.27e-05	5.33e-05	70
hsa0411041	Oral cavity	EOLP	Cell cycle	42/1218	157/8465	3.20e-05	1.61e-04	9.52e-05	42
hsa0411051	Oral cavity	EOLP	Cell cycle	42/1218	157/8465	3.20e-05	1.61e-04	9.52e-05	42
hsa0411061	Oral cavity	NEOLP	Cell cycle	37/1112	157/8465	2.29e-04	1.58e-03	9.95e-04	37
hsa0411071	Oral cavity	NEOLP	Cell cycle	37/1112	157/8465	2.29e-04	1.58e-03	9.95e-04	37

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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

PRKDC

SNV

Missense_Mutation

c.1855G>C

p.Asp619His

p.D619H

P78527

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-3C-AALI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Poly E

Complete Response

PRKDC

SNV

Missense_Mutation

novel

c.3658N>G

p.Leu1220Val

p.L1220V

P78527

protein_coding

deleterious(0.01)

possibly_damaging(0.622)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

PRKDC

SNV

Missense_Mutation

novel

c.1504N>A

p.Glu502Lys

p.E502K

P78527

protein_coding

tolerated(0.18)

benign(0.076)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

PRKDC

SNV

Missense_Mutation

novel

c.5396N>G

p.Glu1799Gly

p.E1799G

P78527

protein_coding

tolerated(0.13)

benign(0.118)

TCGA-A2-A0EQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

PRKDC

SNV

Missense_Mutation

c.9458C>G

p.Ser3153Cys

p.S3153C

P78527

protein_coding

deleterious(0)

possibly_damaging(0.907)

TCGA-A7-A13D-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

PRKDC

SNV

Missense_Mutation

novel

c.5745N>C

p.Leu1915Phe

p.L1915F

P78527

protein_coding

deleterious(0)

probably_damaging(0.914)

TCGA-A7-A6VV-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

PRKDC

SNV

Missense_Mutation

c.2706A>T

p.Lys902Asn

p.K902N

P78527

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-A7-A6VX-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

docetaxel

PRKDC

SNV

Missense_Mutation

c.2210N>T

p.Pro737Leu

p.P737L

P78527

protein_coding

deleterious(0.01)

benign(0.354)

TCGA-A8-A099-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

exemestane

PRKDC

SNV

Missense_Mutation

c.6367N>T

p.Pro2123Ser

p.P2123S

P78527

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PRKDC

SNV

Missense_Mutation

c.3394N>A

p.Asp1132Asn

p.D1132N

P78527

protein_coding

tolerated(0.21)

benign(0.055)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

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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
5591	PRKDC	TRANSCRIPTION FACTOR COMPLEX, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME, PHOSPHATIDYLINOSITOL 3 KINASE, CLINICALLY ACTIONABLE	inhibitor	252827496
5591	PRKDC	TRANSCRIPTION FACTOR COMPLEX, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME, PHOSPHATIDYLINOSITOL 3 KINASE, CLINICALLY ACTIONABLE		M9831
5591	PRKDC	TRANSCRIPTION FACTOR COMPLEX, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME, PHOSPHATIDYLINOSITOL 3 KINASE, CLINICALLY ACTIONABLE		KU-0060648	CHEMBL1086377	23855836
5591	PRKDC	TRANSCRIPTION FACTOR COMPLEX, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME, PHOSPHATIDYLINOSITOL 3 KINASE, CLINICALLY ACTIONABLE	inhibitor	178102582
5591	PRKDC	TRANSCRIPTION FACTOR COMPLEX, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME, PHOSPHATIDYLINOSITOL 3 KINASE, CLINICALLY ACTIONABLE	inhibitor	249565693
5591	PRKDC	TRANSCRIPTION FACTOR COMPLEX, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME, PHOSPHATIDYLINOSITOL 3 KINASE, CLINICALLY ACTIONABLE	inhibitor	354702239
5591	PRKDC	TRANSCRIPTION FACTOR COMPLEX, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME, PHOSPHATIDYLINOSITOL 3 KINASE, CLINICALLY ACTIONABLE	inhibitor	178102681	WORTMANNIN
5591	PRKDC	TRANSCRIPTION FACTOR COMPLEX, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME, PHOSPHATIDYLINOSITOL 3 KINASE, CLINICALLY ACTIONABLE		SF1126
5591	PRKDC	TRANSCRIPTION FACTOR COMPLEX, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME, PHOSPHATIDYLINOSITOL 3 KINASE, CLINICALLY ACTIONABLE	inhibitor	249565692
5591	PRKDC	TRANSCRIPTION FACTOR COMPLEX, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME, PHOSPHATIDYLINOSITOL 3 KINASE, CLINICALLY ACTIONABLE	inhibitor	404859048

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