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: SLK

Gene summary for SLK

Gene summary.

Gene information	Species	Human
	Gene symbol	SLK
	Gene ID	9748
	Gene name	STE20 like kinase
	Gene Alias	LOSK
	Cytomap	10q24.33-q25.1
	Gene Type	protein-coding
	GO ID	GO:0000226
	UniProtAcc	Q9H2G2

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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
9748	SLK	CCI_1	Human	Cervix	CC	1.55e-04	7.48e-01	0.528
9748	SLK	CCI_2	Human	Cervix	CC	5.31e-12	1.09e+00	0.5249
9748	SLK	sample3	Human	Cervix	CC	8.00e-11	3.50e-01	0.1387
9748	SLK	H2	Human	Cervix	HSIL_HPV	2.28e-05	3.65e-01	0.0632
9748	SLK	T3	Human	Cervix	CC	6.73e-11	3.67e-01	0.1389
9748	SLK	HTA11_3410_2000001011	Human	Colorectum	AD	4.10e-03	-3.46e-01	0.0155
9748	SLK	HTA11_347_2000001011	Human	Colorectum	AD	1.66e-02	2.70e-01	-0.1954
9748	SLK	HTA11_99999974143_84620	Human	Colorectum	MSS	2.55e-07	-4.00e-01	0.3005
9748	SLK	A015-C-203	Human	Colorectum	FAP	8.84e-14	-6.08e-02	-0.1294
9748	SLK	A002-C-201	Human	Colorectum	FAP	2.20e-06	-7.81e-02	0.0324
9748	SLK	A001-C-119	Human	Colorectum	FAP	4.37e-02	3.61e-02	-0.1557
9748	SLK	A001-C-108	Human	Colorectum	FAP	1.42e-11	3.04e-01	-0.0272
9748	SLK	A002-C-205	Human	Colorectum	FAP	2.03e-15	8.12e-02	-0.1236
9748	SLK	A015-C-006	Human	Colorectum	FAP	6.32e-12	1.90e-01	-0.0994
9748	SLK	A015-C-106	Human	Colorectum	FAP	1.28e-06	6.84e-02	-0.0511
9748	SLK	A002-C-114	Human	Colorectum	FAP	1.16e-12	6.58e-02	-0.1561
9748	SLK	A015-C-104	Human	Colorectum	FAP	4.31e-19	9.81e-02	-0.1899
9748	SLK	A001-C-014	Human	Colorectum	FAP	1.06e-06	2.21e-01	0.0135
9748	SLK	A002-C-016	Human	Colorectum	FAP	7.79e-09	2.43e-02	0.0521
9748	SLK	A015-C-002	Human	Colorectum	FAP	1.17e-05	-1.60e-01	-0.0763

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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
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
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:001081017	Prostate	BPH	regulation of cell-substrate adhesion	74/3107	221/18723	5.40e-10	2.70e-08	74
GO:00480419	Prostate	BPH	focal adhesion assembly	39/3107	87/18723	6.07e-10	2.91e-08	39
GO:005189310	Prostate	BPH	regulation of focal adhesion assembly	32/3107	66/18723	1.85e-09	7.63e-08	32
GO:009010910	Prostate	BPH	regulation of cell-substrate junction assembly	32/3107	66/18723	1.85e-09	7.63e-08	32
GO:000195210	Prostate	BPH	regulation of cell-matrix adhesion	48/3107	128/18723	9.98e-09	3.34e-07	48
GO:003432910	Prostate	BPH	cell junction assembly	114/3107	420/18723	2.52e-08	7.49e-07	114
GO:000716010	Prostate	BPH	cell-matrix adhesion	72/3107	233/18723	4.17e-08	1.16e-06	72
GO:19018888	Prostate	BPH	regulation of cell junction assembly	62/3107	204/18723	6.71e-07	1.30e-05	62
GO:00311225	Prostate	BPH	cytoplasmic microtubule organization	22/3107	56/18723	4.21e-05	4.48e-04	22
GO:00467778	Prostate	BPH	protein autophosphorylation	52/3107	227/18723	8.26e-03	3.59e-02	52
GO:015011516	Prostate	Tumor	cell-substrate junction organization	46/3246	101/18723	4.27e-11	2.82e-09	46
GO:000704415	Prostate	Tumor	cell-substrate junction assembly	43/3246	95/18723	2.33e-10	1.34e-08	43
GO:003158916	Prostate	Tumor	cell-substrate adhesion	109/3246	363/18723	1.41e-09	6.71e-08	109
GO:015011616	Prostate	Tumor	regulation of cell-substrate junction organization	34/3246	71/18723	2.86e-09	1.18e-07	34
GO:001081018	Prostate	Tumor	regulation of cell-substrate adhesion	73/3246	221/18723	9.68e-09	3.62e-07	73
GO:005189315	Prostate	Tumor	regulation of focal adhesion assembly	31/3246	66/18723	2.52e-08	8.33e-07	31
GO:009010915	Prostate	Tumor	regulation of cell-substrate junction assembly	31/3246	66/18723	2.52e-08	8.33e-07	31
GO:004804114	Prostate	Tumor	focal adhesion assembly	36/3246	87/18723	1.15e-07	3.01e-06	36
GO:000195214	Prostate	Tumor	regulation of cell-matrix adhesion	47/3246	128/18723	1.20e-07	3.14e-06	47
GO:003432915	Prostate	Tumor	cell junction assembly	113/3246	420/18723	4.94e-07	1.07e-05	113

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa041146	Esophagus	ESCC	Oocyte meiosis	77/4205	131/8465	2.19e-02	4.80e-02	2.46e-02	77
hsa0411411	Esophagus	ESCC	Oocyte meiosis	77/4205	131/8465	2.19e-02	4.80e-02	2.46e-02	77
hsa04114	Oral cavity	OSCC	Oocyte meiosis	74/3704	131/8465	2.13e-03	5.75e-03	2.92e-03	74
hsa041141	Oral cavity	OSCC	Oocyte meiosis	74/3704	131/8465	2.13e-03	5.75e-03	2.92e-03	74
hsa041142	Oral cavity	EOLP	Oocyte meiosis	33/1218	131/8465	7.09e-04	2.69e-03	1.59e-03	33
hsa041143	Oral cavity	EOLP	Oocyte meiosis	33/1218	131/8465	7.09e-04	2.69e-03	1.59e-03	33
hsa041144	Oral cavity	NEOLP	Oocyte meiosis	31/1112	131/8465	6.64e-04	3.52e-03	2.21e-03	31
hsa041145	Oral cavity	NEOLP	Oocyte meiosis	31/1112	131/8465	6.64e-04	3.52e-03	2.21e-03	31

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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

SLK

SNV

Missense_Mutation

rs771440768

c.1735N>A

p.Glu579Lys

p.E579K

Q9H2G2

protein_coding

tolerated(0.74)

benign(0.001)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SLK

SNV

Missense_Mutation

novel

c.3034N>A

p.Glu1012Lys

p.E1012K

Q9H2G2

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-AO-A0JC-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

fluorouracil

SLK

SNV

Missense_Mutation

c.1360N>T

p.Asn454Tyr

p.N454Y

Q9H2G2

protein_coding

deleterious(0.01)

benign(0.115)

TCGA-BH-A0DK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

SLK

SNV

Missense_Mutation

c.688N>A

p.Glu230Lys

p.E230K

Q9H2G2

protein_coding

deleterious(0)

benign(0.175)

TCGA-D8-A27G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SLK

SNV

Missense_Mutation

novel

c.179N>A

p.Ala60Asp

p.A60D

Q9H2G2

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-C5-A8YQ-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

SLK

SNV

Missense_Mutation

novel

c.2483G>A

p.Arg828His

p.R828H

Q9H2G2

protein_coding

deleterious(0.01)

probably_damaging(0.998)

TCGA-EA-A3HS-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SLK

SNV

Missense_Mutation

c.1618N>T

p.Asp540Tyr

p.D540Y

Q9H2G2

protein_coding

deleterious(0.01)

benign(0)

TCGA-FU-A3HZ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SLK

SNV

Missense_Mutation

rs554070501

c.2774N>A

p.Arg925Gln

p.R925Q

Q9H2G2

protein_coding

tolerated(0.06)

possibly_damaging(0.453)

TCGA-FU-A3HZ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SLK

SNV

Missense_Mutation

c.64N>A

p.Glu22Lys

p.E22K

Q9H2G2

protein_coding

deleterious(0)

probably_damaging(0.97)

TCGA-IR-A3LK-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

SLK

insertion

Nonsense_Mutation

novel

c.2732_2733insTAACTAGTATTTAAATTT

p.Gln911delinsHisAsnTerTyrLeuAsnLeu

p.Q911delinsHN*YLNL

Q9H2G2

protein_coding

TCGA-DS-A1OD-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

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
9748	SLK	DRUGGABLE GENOME, ENZYME, SERINE THREONINE KINASE, KINASE		ALISERTIB	ALISERTIB
9748	SLK	DRUGGABLE GENOME, ENZYME, SERINE THREONINE KINASE, KINASE		CYC-116	CYC-116
9748	SLK	DRUGGABLE GENOME, ENZYME, SERINE THREONINE KINASE, KINASE	inhibitor	249565620	DANUSERTIB
9748	SLK	DRUGGABLE GENOME, ENZYME, SERINE THREONINE KINASE, KINASE		SNS-314	SNS-314
9748	SLK	DRUGGABLE GENOME, ENZYME, SERINE THREONINE KINASE, KINASE		OSI-632	OSI-632
9748	SLK	DRUGGABLE GENOME, ENZYME, SERINE THREONINE KINASE, KINASE		ENTRECTINIB	ENTRECTINIB
9748	SLK	DRUGGABLE GENOME, ENZYME, SERINE THREONINE KINASE, KINASE		BAY-613606	CHEMBL541400
9748	SLK	DRUGGABLE GENOME, ENZYME, SERINE THREONINE KINASE, KINASE		RG-1530	RG-1530
9748	SLK	DRUGGABLE GENOME, ENZYME, SERINE THREONINE KINASE, KINASE		GEFITINIB	GEFITINIB
9748	SLK	DRUGGABLE GENOME, ENZYME, SERINE THREONINE KINASE, KINASE		GW441756X	GW441756X

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