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: CAMK2N1

Gene summary for CAMK2N1

Gene summary.

Gene information	Species	Human
	Gene symbol	CAMK2N1
	Gene ID	55450
	Gene name	calcium/calmodulin dependent protein kinase II inhibitor 1
	Gene Alias	PRO1489
	Cytomap	1p36.12
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	Q7Z7J9

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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
55450	CAMK2N1	GSM4909285	Human	Breast	IDC	3.78e-02	-1.77e-01	0.21
55450	CAMK2N1	GSM4909286	Human	Breast	IDC	1.03e-04	-2.03e-01	0.1081
55450	CAMK2N1	GSM4909287	Human	Breast	IDC	4.38e-07	-2.14e-01	0.2057
55450	CAMK2N1	GSM4909290	Human	Breast	IDC	1.81e-04	-2.14e-01	0.2096
55450	CAMK2N1	GSM4909291	Human	Breast	IDC	1.25e-11	5.38e-01	0.1753
55450	CAMK2N1	GSM4909293	Human	Breast	IDC	8.37e-06	2.98e-01	0.1581
55450	CAMK2N1	GSM4909294	Human	Breast	IDC	3.10e-02	2.50e-01	0.2022
55450	CAMK2N1	GSM4909297	Human	Breast	IDC	5.90e-04	3.04e-01	0.1517
55450	CAMK2N1	GSM4909298	Human	Breast	IDC	3.35e-09	3.32e-01	0.1551
55450	CAMK2N1	GSM4909306	Human	Breast	IDC	1.27e-02	2.55e-01	0.1564
55450	CAMK2N1	GSM4909307	Human	Breast	IDC	2.07e-03	-1.80e-01	0.1569
55450	CAMK2N1	GSM4909308	Human	Breast	IDC	1.11e-03	-2.07e-01	0.158
55450	CAMK2N1	GSM4909311	Human	Breast	IDC	6.00e-06	-9.27e-02	0.1534
55450	CAMK2N1	GSM4909317	Human	Breast	IDC	2.93e-09	3.02e-01	0.1355
55450	CAMK2N1	GSM4909319	Human	Breast	IDC	9.19e-07	-1.63e-01	0.1563
55450	CAMK2N1	GSM4909321	Human	Breast	IDC	2.64e-07	3.73e-01	0.1559
55450	CAMK2N1	brca2	Human	Breast	Precancer	6.22e-04	1.16e-01	-0.024
55450	CAMK2N1	brca3	Human	Breast	Precancer	3.00e-04	1.62e-01	-0.0263
55450	CAMK2N1	NCCBC14	Human	Breast	DCIS	3.01e-23	8.46e-01	0.2021
55450	CAMK2N1	NCCBC5	Human	Breast	DCIS	2.16e-03	3.30e-01	0.2046

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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
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
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
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:004593618	Prostate	BPH	negative regulation of phosphate metabolic process	124/3107	441/18723	5.95e-10	2.90e-08	124
GO:005122217	Prostate	BPH	positive regulation of protein transport	93/3107	303/18723	6.94e-10	3.25e-08	93
GO:001056318	Prostate	BPH	negative regulation of phosphorus metabolic process	124/3107	442/18723	6.94e-10	3.25e-08	124
GO:004232617	Prostate	BPH	negative regulation of phosphorylation	110/3107	385/18723	2.08e-09	8.35e-08	110
GO:000193317	Prostate	BPH	negative regulation of protein phosphorylation	97/3107	342/18723	2.74e-08	8.11e-07	97
GO:004586118	Prostate	BPH	negative regulation of proteolysis	98/3107	351/18723	5.43e-08	1.49e-06	98
GO:005134818	Prostate	BPH	negative regulation of transferase activity	78/3107	268/18723	1.94e-07	4.29e-06	78
GO:000646916	Prostate	BPH	negative regulation of protein kinase activity	62/3107	212/18723	2.81e-06	4.45e-05	62
GO:003367315	Prostate	BPH	negative regulation of kinase activity	67/3107	237/18723	4.15e-06	6.25e-05	67
GO:19040292	Prostate	BPH	regulation of cyclin-dependent protein kinase activity	34/3107	98/18723	1.00e-05	1.39e-04	34
GO:000974318	Prostate	BPH	response to carbohydrate	67/3107	253/18723	4.20e-05	4.48e-04	67
GO:003428418	Prostate	BPH	response to monosaccharide	61/3107	225/18723	4.34e-05	4.60e-04	61
GO:004340915	Prostate	BPH	negative regulation of MAPK cascade	51/3107	180/18723	5.20e-05	5.35e-04	51
GO:000974617	Prostate	BPH	response to hexose	58/3107	219/18723	1.33e-04	1.19e-03	58
GO:00457863	Prostate	BPH	negative regulation of cell cycle	91/3107	385/18723	2.10e-04	1.71e-03	91
GO:000974915	Prostate	BPH	response to glucose	55/3107	212/18723	3.42e-04	2.55e-03	55
GO:1904030	Prostate	BPH	negative regulation of cyclin-dependent protein kinase activity	14/3107	33/18723	4.08e-04	2.97e-03	14
GO:000167810	Prostate	BPH	cellular glucose homeostasis	44/3107	172/18723	1.71e-03	9.87e-03	44
GO:007133310	Prostate	BPH	cellular response to glucose stimulus	39/3107	151/18723	2.52e-03	1.35e-02	39
GO:00716928	Prostate	BPH	protein localization to extracellular region	82/3107	368/18723	2.59e-03	1.39e-02	82

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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

CAMK2N1

SNV

Missense_Mutation

novel

c.203N>C

p.Lys68Thr

p.K68T

Q7Z7J9

protein_coding

deleterious_low_confidence(0.01)

possibly_damaging(0.563)

TCGA-AJ-A5DW-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

CAMK2N1

SNV

Missense_Mutation

novel

c.196N>A

p.Val66Met

p.V66M

Q7Z7J9

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.706)

TCGA-AP-A1DK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

CAMK2N1

SNV

Missense_Mutation

novel

c.185G>T

p.Arg62Met

p.R62M

Q7Z7J9

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.993)

TCGA-FI-A2D5-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatinum

CAMK2N1

SNV

Missense_Mutation

c.113N>G

p.Ala38Gly

p.A38G

Q7Z7J9

protein_coding

tolerated_low_confidence(1)

benign(0)

TCGA-CC-A7IH-01

Liver

liver hepatocellular carcinoma

Male

<65

III/IV

Unknown

CAMK2N1

SNV

Missense_Mutation

c.219N>T

p.Lys73Asn

p.K73N

Q7Z7J9

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(0.991)

TCGA-50-5930-01

Lung

lung adenocarcinoma

Male

<65

III/IV

Chemotherapy

taxotere

CAMK2N1

SNV

Missense_Mutation

novel

c.195N>A

p.Asp65Glu

p.D65E

Q7Z7J9

protein_coding

tolerated_low_confidence(0.57)

benign(0.005)

TCGA-78-7155-01

Lung

lung adenocarcinoma

Male

>=65

I/II

Chemotherapy

carboplatin

CAMK2N1

SNV

Missense_Mutation

c.95N>A

p.Thr32Asn

p.T32N

Q7Z7J9

protein_coding

deleterious_low_confidence(0.01)

benign(0)

TCGA-97-7937-01

Lung

lung adenocarcinoma

Male

>=65

I/II

Unknown

CAMK2N1

SNV

Missense_Mutation

novel

c.220N>T

p.Ala74Ser

p.A74S

Q7Z7J9

protein_coding

tolerated_low_confidence(1)

benign(0.003)

TCGA-39-5040-01

Lung

lung squamous cell carcinoma

Male

<65

III/IV

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

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