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: CASK

Gene summary for CASK

Gene summary.

Gene information	Species	Human
	Gene symbol	CASK
	Gene ID	8573
	Gene name	calcium/calmodulin dependent serine protein kinase
	Gene Alias	CAGH39
	Cytomap	Xp11.4
	Gene Type	protein-coding
	GO ID	GO:0001505
	UniProtAcc	O14936

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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
8573	CASK	SYSMH1	Human	Oral cavity	OSCC	4.45e-29	7.24e-01	0.1127
8573	CASK	SYSMH2	Human	Oral cavity	OSCC	1.83e-07	1.91e-01	0.2326
8573	CASK	SYSMH3	Human	Oral cavity	OSCC	5.59e-10	3.63e-01	0.2442
8573	CASK	SYSMH6	Human	Oral cavity	OSCC	5.46e-05	9.14e-02	0.1275
8573	CASK	HTA12-26-1	Human	Pancreas	PDAC	4.12e-10	6.97e-01	0.3728
8573	CASK	HTA12-29-1	Human	Pancreas	PDAC	2.68e-19	5.13e-01	0.3722
8573	CASK	GSM5252132_BPH389PrGF	Human	Prostate	BPH	1.35e-03	3.82e-01	-0.2247
8573	CASK	GSM5252137_BPH556PrGA2_Fcol	Human	Prostate	BPH	4.96e-04	2.69e-01	-0.23
8573	CASK	047563_1562-all-cells	Human	Prostate	BPH	3.03e-11	4.22e-01	0.0791
8573	CASK	048752_1579-all-cells	Human	Prostate	BPH	1.98e-11	4.08e-01	0.1008
8573	CASK	052095_1628-all-cells	Human	Prostate	BPH	5.49e-20	4.86e-01	0.1032
8573	CASK	052097_1595-all-cells	Human	Prostate	BPH	1.07e-28	6.39e-01	0.0972
8573	CASK	052099_1652-all-cells	Human	Prostate	BPH	2.76e-22	5.86e-01	0.1038
8573	CASK	Dong_P1	Human	Prostate	Tumor	4.70e-06	6.06e-02	0.035
8573	CASK	Dong_P3	Human	Prostate	Tumor	1.23e-02	6.68e-02	0.0278
8573	CASK	Dong_P5	Human	Prostate	Tumor	3.73e-03	3.57e-03	0.053
8573	CASK	GSM5353221_PA_PB2A_Pool_1_3_S25_L001	Human	Prostate	Tumor	2.59e-02	3.82e-01	0.1633
8573	CASK	P1_S1_AK	Human	Skin	AK	3.52e-28	7.49e-01	-0.3399
8573	CASK	P2_S3_AK	Human	Skin	AK	1.36e-11	4.74e-01	-0.3287
8573	CASK	P3_S6_AK	Human	Skin	AK	3.30e-06	3.41e-01	-0.3256

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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
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
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

∗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:004206010	Cervix	CC	wound healing	109/2311	422/18723	1.84e-14	1.57e-11	109
GO:001081010	Cervix	CC	regulation of cell-substrate adhesion	69/2311	221/18723	8.57e-14	5.69e-11	69
GO:00315898	Cervix	CC	cell-substrate adhesion	96/2311	363/18723	1.48e-13	8.85e-11	96
GO:00506737	Cervix	CC	epithelial cell proliferation	98/2311	437/18723	2.01e-09	2.15e-07	98
GO:00019528	Cervix	CC	regulation of cell-matrix adhesion	40/2311	128/18723	1.32e-08	1.04e-06	40
GO:00071608	Cervix	CC	cell-matrix adhesion	60/2311	233/18723	1.58e-08	1.23e-06	60
GO:00071626	Cervix	CC	negative regulation of cell adhesion	72/2311	303/18723	2.36e-08	1.70e-06	72
GO:00506787	Cervix	CC	regulation of epithelial cell proliferation	83/2311	381/18723	1.31e-07	6.42e-06	83
GO:19030349	Cervix	CC	regulation of response to wounding	44/2311	167/18723	6.33e-07	2.31e-05	44
GO:00610418	Cervix	CC	regulation of wound healing	34/2311	134/18723	2.70e-05	4.52e-04	34
GO:00108122	Cervix	CC	negative regulation of cell-substrate adhesion	21/2311	68/18723	4.35e-05	6.66e-04	21
GO:00436164	Cervix	CC	keratinocyte proliferation	15/2311	46/18723	2.70e-04	2.97e-03	15
GO:00196939	Cervix	CC	ribose phosphate metabolic process	72/2311	396/18723	4.49e-04	4.48e-03	72
GO:00092599	Cervix	CC	ribonucleotide metabolic process	70/2311	385/18723	5.35e-04	5.18e-03	70
GO:00321022	Cervix	CC	negative regulation of response to external stimulus	75/2311	420/18723	5.96e-04	5.61e-03	75
GO:00108376	Cervix	CC	regulation of keratinocyte proliferation	12/2311	35/18723	6.55e-04	6.05e-03	12
GO:000915010	Cervix	CC	purine ribonucleotide metabolic process	66/2311	368/18723	1.09e-03	9.07e-03	66
GO:00171574	Cervix	CC	regulation of exocytosis	39/2311	202/18723	2.90e-03	1.93e-02	39
GO:000616310	Cervix	CC	purine nucleotide metabolic process	67/2311	396/18723	4.41e-03	2.69e-02	67
GO:007252110	Cervix	CC	purine-containing compound metabolic process	69/2311	416/18723	6.27e-03	3.54e-02	69

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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

CASK

SNV

Missense_Mutation

c.2668N>G

p.Ile890Val

p.I890V

O14936

protein_coding

tolerated(1)

benign(0)

TCGA-A1-A0SD-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CASK

SNV

Missense_Mutation

c.1870G>C

p.Asp624His

p.D624H

O14936

protein_coding

deleterious(0)

probably_damaging(0.965)

TCGA-A2-A04R-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxol

CASK

SNV

Missense_Mutation

c.1727N>T

p.Ser576Leu

p.S576L

O14936

protein_coding

tolerated(0.17)

benign(0)

TCGA-A2-A0YT-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

arimidex

CASK

SNV

Missense_Mutation

novel

c.527N>G

p.Ala176Gly

p.A176G

O14936

protein_coding

tolerated(0.25)

benign(0.017)

TCGA-A2-A4S1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CASK

SNV

Missense_Mutation

c.847G>A

p.Ala283Thr

p.A283T

O14936

protein_coding

deleterious(0.02)

benign(0.098)

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

CASK

SNV

Missense_Mutation

novel

c.1521G>A

p.Met507Ile

p.M507I

O14936

protein_coding

tolerated(0.25)

benign(0.015)

TCGA-BH-A2L8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

CASK

SNV

Missense_Mutation

c.2454N>G

p.Ile818Met

p.I818M

O14936

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-C8-A26Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CASK

SNV

Missense_Mutation

c.1916N>A

p.Arg639Gln

p.R639Q

O14936

protein_coding

tolerated(0.52)

benign(0.313)

TCGA-D8-A27G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CASK

insertion

Frame_Shift_Ins

novel

c.14_15insGTTGGGGTTATTGTTACCTTGCATGTACCATAGACCATTTTTGAAAC

p.Asp5GlufsTer29

p.D5Efs*29

O14936

protein_coding

TCGA-AN-A0FX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CASK

insertion

Frame_Shift_Ins

novel

c.1519dupA

p.Met507AsnfsTer3

p.M507Nfs*3

O14936

protein_coding

TCGA-BH-A2L8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

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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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