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: STK24

Gene summary for STK24

Gene summary.

Gene information	Species	Human
	Gene symbol	STK24
	Gene ID	8428
	Gene name	serine/threonine kinase 24
	Gene Alias	HEL-S-95
	Cytomap	13q32.2
	Gene Type	protein-coding
	GO ID	GO:0000302
	UniProtAcc	Q5U0E6

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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
8428	STK24	CCI_1	Human	Cervix	CC	2.33e-09	1.03e+00	0.528
8428	STK24	CCI_2	Human	Cervix	CC	2.27e-13	1.67e+00	0.5249
8428	STK24	CCI_3	Human	Cervix	CC	3.57e-17	1.18e+00	0.516
8428	STK24	Tumor	Human	Cervix	CC	2.60e-03	3.04e-01	0.1241
8428	STK24	sample3	Human	Cervix	CC	3.11e-08	3.72e-01	0.1387
8428	STK24	T3	Human	Cervix	CC	8.74e-13	3.77e-01	0.1389
8428	STK24	HTA11_3410_2000001011	Human	Colorectum	AD	1.20e-06	-4.30e-01	0.0155
8428	STK24	HTA11_866_3004761011	Human	Colorectum	AD	8.58e-06	-4.21e-01	0.096
8428	STK24	HTA11_7696_3000711011	Human	Colorectum	AD	6.99e-05	-3.49e-01	0.0674
8428	STK24	HTA11_99999970781_79442	Human	Colorectum	MSS	5.83e-07	-3.50e-01	0.294
8428	STK24	HTA11_99999974143_84620	Human	Colorectum	MSS	8.19e-09	-4.13e-01	0.3005
8428	STK24	A015-C-203	Human	Colorectum	FAP	7.15e-22	-3.85e-01	-0.1294
8428	STK24	A015-C-204	Human	Colorectum	FAP	2.45e-06	-3.40e-01	-0.0228
8428	STK24	A014-C-040	Human	Colorectum	FAP	6.63e-03	-2.30e-01	-0.1184
8428	STK24	A002-C-201	Human	Colorectum	FAP	2.65e-11	-2.86e-01	0.0324
8428	STK24	A002-C-203	Human	Colorectum	FAP	1.87e-02	-1.28e-01	0.2786
8428	STK24	A001-C-119	Human	Colorectum	FAP	4.36e-05	-2.68e-01	-0.1557
8428	STK24	A001-C-108	Human	Colorectum	FAP	1.55e-13	-3.14e-01	-0.0272
8428	STK24	A002-C-205	Human	Colorectum	FAP	1.47e-18	-3.64e-01	-0.1236
8428	STK24	A001-C-104	Human	Colorectum	FAP	1.38e-03	-1.52e-01	0.0184

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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
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:00310992	Liver	HCC	regeneration	107/7958	198/18723	6.67e-04	4.12e-03	107
GO:001097511	Liver	HCC	regulation of neuron projection development	220/7958	445/18723	1.68e-03	8.78e-03	220
GO:003647312	Liver	HCC	cell death in response to oxidative stress	55/7958	95/18723	1.76e-03	9.12e-03	55
GO:0097194	Liver	HCC	execution phase of apoptosis	48/7958	85/18723	6.47e-03	2.63e-02	48
GO:00971938	Lung	IAC	intrinsic apoptotic signaling pathway	72/2061	288/18723	1.36e-11	4.83e-09	72
GO:00467776	Lung	IAC	protein autophosphorylation	51/2061	227/18723	4.85e-07	3.10e-05	51
GO:00109756	Lung	IAC	regulation of neuron projection development	82/2061	445/18723	1.82e-06	8.78e-05	82
GO:00069798	Lung	IAC	response to oxidative stress	82/2061	446/18723	1.99e-06	9.18e-05	82
GO:00621978	Lung	IAC	cellular response to chemical stress	64/2061	337/18723	8.92e-06	3.01e-04	64
GO:00714968	Lung	IAC	cellular response to external stimulus	60/2061	320/18723	2.50e-05	6.76e-04	60
GO:00316687	Lung	IAC	cellular response to extracellular stimulus	48/2061	246/18723	5.62e-05	1.24e-03	48
GO:00345998	Lung	IAC	cellular response to oxidative stress	54/2061	288/18723	6.20e-05	1.35e-03	54
GO:00003028	Lung	IAC	response to reactive oxygen species	44/2061	222/18723	7.69e-05	1.59e-03	44
GO:00615646	Lung	IAC	axon development	78/2061	467/18723	1.12e-04	2.15e-03	78
GO:00316696	Lung	IAC	cellular response to nutrient levels	41/2061	215/18723	3.13e-04	4.98e-03	41
GO:00316678	Lung	IAC	response to nutrient levels	76/2061	474/18723	4.87e-04	7.08e-03	76
GO:00425428	Lung	IAC	response to hydrogen peroxide	28/2061	146/18723	2.39e-03	2.31e-02	28
GO:00364738	Lung	IAC	cell death in response to oxidative stress	20/2061	95/18723	3.15e-03	2.75e-02	20
GO:00092676	Lung	IAC	cellular response to starvation	29/2061	156/18723	3.26e-03	2.80e-02	29
GO:2000146	Lung	IAC	negative regulation of cell motility	56/2061	359/18723	4.58e-03	3.62e-02	56

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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

STK24

SNV

Missense_Mutation

novel

c.1008N>G

p.Asp336Glu

p.D336E

Q9Y6E0

protein_coding

tolerated(0.65)

benign(0)

TCGA-AC-A3W5-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

docetaxel

STK24

SNV

Missense_Mutation

novel

c.225N>T

p.Glu75Asp

p.E75D

Q9Y6E0

protein_coding

tolerated(0.13)

benign(0.125)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

STK24

SNV

Missense_Mutation

novel

c.1153G>A

p.Ala385Thr

p.A385T

Q9Y6E0

protein_coding

tolerated_low_confidence(0.21)

benign(0.003)

TCGA-EW-A6SB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

STK24

SNV

Missense_Mutation

rs748012213

c.952G>A

p.Glu318Lys

p.E318K

Q9Y6E0

protein_coding

tolerated(0.11)

benign(0.251)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

STK24

SNV

Missense_Mutation

novel

c.1254N>G

p.Ile418Met

p.I418M

Q9Y6E0

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.861)

TCGA-VS-A8EL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

STK24

SNV

Missense_Mutation

rs200464604

c.1214N>A

p.Arg405Gln

p.R405Q

Q9Y6E0

protein_coding

tolerated_low_confidence(0.15)

benign(0.001)

TCGA-VS-A9V2-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

STK24

SNV

Missense_Mutation

c.113A>C

p.Lys38Thr

p.K38T

Q9Y6E0

protein_coding

deleterious(0.04)

possibly_damaging(0.74)

TCGA-A6-6141-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Chemotherapy

5-fu

STK24

SNV

Missense_Mutation

c.493N>C

p.Ser165Pro

p.S165P

Q9Y6E0

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-AA-3663-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

STK24

SNV

Missense_Mutation

rs367740523

c.355G>A

p.Ala119Thr

p.A119T

Q9Y6E0

protein_coding

deleterious(0)

probably_damaging(0.963)

TCGA-AA-3864-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

STK24

SNV

Missense_Mutation

novel

c.892G>A

p.Glu298Lys

p.E298K

Q9Y6E0

protein_coding

deleterious(0)

possibly_damaging(0.588)

TCGA-AA-3984-01

Colorectum

colon adenocarcinoma

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
8428	STK24	KINASE, DRUGGABLE GENOME, SERINE THREONINE KINASE, ENZYME	inhibitor	178102336	BOSUTINIB

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