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: CDK10

Gene summary for CDK10

Gene summary.

Gene information	Species	Human
	Gene symbol	CDK10
	Gene ID	8558
	Gene name	cyclin dependent kinase 10
	Gene Alias	ALSAS
	Cytomap	16q24.3
	Gene Type	protein-coding
	GO ID	GO:0000082
	UniProtAcc	B7Z537

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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
8558	CDK10	LZE4T	Human	Esophagus	ESCC	2.50e-09	2.56e-01	0.0811
8558	CDK10	LZE7T	Human	Esophagus	ESCC	5.13e-11	3.45e-01	0.0667
8558	CDK10	LZE8T	Human	Esophagus	ESCC	2.14e-08	2.46e-01	0.067
8558	CDK10	LZE20T	Human	Esophagus	ESCC	5.05e-10	2.41e-01	0.0662
8558	CDK10	LZE21D1	Human	Esophagus	HGIN	6.01e-03	3.55e-01	0.0632
8558	CDK10	LZE22D1	Human	Esophagus	HGIN	1.02e-02	1.85e-01	0.0595
8558	CDK10	LZE22T	Human	Esophagus	ESCC	2.08e-06	3.95e-01	0.068
8558	CDK10	LZE24T	Human	Esophagus	ESCC	3.03e-15	3.03e-01	0.0596
8558	CDK10	LZE21T	Human	Esophagus	ESCC	8.30e-04	3.58e-01	0.0655
8558	CDK10	P1T-E	Human	Esophagus	ESCC	6.15e-12	5.14e-01	0.0875
8558	CDK10	P2T-E	Human	Esophagus	ESCC	2.34e-27	3.89e-01	0.1177
8558	CDK10	P4T-E	Human	Esophagus	ESCC	3.13e-20	4.11e-01	0.1323
8558	CDK10	P5T-E	Human	Esophagus	ESCC	6.26e-27	2.64e-01	0.1327
8558	CDK10	P8T-E	Human	Esophagus	ESCC	3.72e-28	5.10e-01	0.0889
8558	CDK10	P9T-E	Human	Esophagus	ESCC	3.27e-10	1.70e-01	0.1131
8558	CDK10	P10T-E	Human	Esophagus	ESCC	2.79e-19	3.05e-01	0.116
8558	CDK10	P11T-E	Human	Esophagus	ESCC	1.35e-12	4.20e-01	0.1426
8558	CDK10	P12T-E	Human	Esophagus	ESCC	2.00e-32	5.13e-01	0.1122
8558	CDK10	P15T-E	Human	Esophagus	ESCC	1.35e-22	3.49e-01	0.1149
8558	CDK10	P16T-E	Human	Esophagus	ESCC	3.30e-17	3.10e-01	0.1153

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:001063920	Esophagus	HGIN	negative regulation of organelle organization	79/2587	348/18723	4.12e-06	1.37e-04	79
GO:000734610	Esophagus	HGIN	regulation of mitotic cell cycle	98/2587	457/18723	4.39e-06	1.42e-04	98
GO:00447729	Esophagus	HGIN	mitotic cell cycle phase transition	89/2587	424/18723	2.80e-05	7.21e-04	89
GO:19021156	Esophagus	HGIN	regulation of organelle assembly	46/2587	186/18723	4.63e-05	1.12e-03	46
GO:19019906	Esophagus	HGIN	regulation of mitotic cell cycle phase transition	65/2587	299/18723	1.12e-04	2.36e-03	65
GO:20000456	Esophagus	HGIN	regulation of G1/S transition of mitotic cell cycle	36/2587	142/18723	1.74e-04	3.35e-03	36
GO:00000827	Esophagus	HGIN	G1/S transition of mitotic cell cycle	48/2587	214/18723	3.97e-04	6.07e-03	48
GO:00448437	Esophagus	HGIN	cell cycle G1/S phase transition	52/2587	241/18723	6.19e-04	8.58e-03	52
GO:19028065	Esophagus	HGIN	regulation of cell cycle G1/S phase transition	39/2587	168/18723	6.60e-04	9.03e-03	39
GO:003297027	Esophagus	HGIN	regulation of actin filament-based process	77/2587	397/18723	1.14e-03	1.39e-02	77
GO:003295627	Esophagus	HGIN	regulation of actin cytoskeleton organization	69/2587	358/18723	2.35e-03	2.39e-02	69
GO:19021162	Esophagus	HGIN	negative regulation of organelle assembly	13/2587	41/18723	2.62e-03	2.58e-02	13
GO:004593110	Esophagus	HGIN	positive regulation of mitotic cell cycle	28/2587	121/18723	3.72e-03	3.39e-02	28
GO:006049117	Esophagus	HGIN	regulation of cell projection assembly	39/2587	188/18723	5.61e-03	4.57e-02	39
GO:19019876	Esophagus	HGIN	regulation of cell cycle phase transition	72/2587	390/18723	5.78e-03	4.70e-02	72
GO:004477216	Esophagus	ESCC	mitotic cell cycle phase transition	281/8552	424/18723	4.63e-18	4.45e-16	281
GO:000734615	Esophagus	ESCC	regulation of mitotic cell cycle	293/8552	457/18723	8.00e-16	5.64e-14	293
GO:190198713	Esophagus	ESCC	regulation of cell cycle phase transition	242/8552	390/18723	3.86e-11	1.26e-09	242
GO:190199013	Esophagus	ESCC	regulation of mitotic cell cycle phase transition	191/8552	299/18723	1.35e-10	3.94e-09	191
GO:0010639110	Esophagus	ESCC	negative regulation of organelle organization	215/8552	348/18723	8.20e-10	2.01e-08	215

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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

CDK10

SNV

Missense_Mutation

rs369118585

c.58N>A

p.Gly20Ser

p.G20S

Q15131

protein_coding

tolerated(0.37)

benign(0.003)

TCGA-A2-A0CP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

CDK10

SNV

Missense_Mutation

c.365A>G

p.Gln122Arg

p.Q122R

Q15131

protein_coding

deleterious(0)

possibly_damaging(0.596)

TCGA-AR-A252-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

CDK10

SNV

Missense_Mutation

c.995C>A

p.Pro332Gln

p.P332Q

Q15131

protein_coding

deleterious(0.01)

possibly_damaging(0.862)

TCGA-D8-A27E-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen+anastrazolum

CDK10

SNV

Missense_Mutation

c.77N>G

p.Pro26Arg

p.P26R

Q15131

protein_coding

tolerated(0.07)

benign(0.062)

TCGA-E9-A1NA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

CDK10

insertion

In_Frame_Ins

novel

c.552_553insCTCACGCCTGTGATCCCAGCACTTTTGGGA

p.Leu184_Ala185insLeuThrProValIleProAlaLeuLeuGly

p.L184_A185insLTPVIPALLG

Q15131

protein_coding

TCGA-AO-A0JF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

CDK10

insertion

Nonsense_Mutation

novel

c.598_599insGGTTTCCAACTTGCTCATGACCGACAAGGGT

p.Val200GlyfsTer7

p.V200Gfs*7

Q15131

protein_coding

TCGA-BH-A0HQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

CDK10

SNV

Missense_Mutation

rs145469184

c.661G>A

p.Asp221Asn

p.D221N

Q15131

protein_coding

deleterious(0)

probably_damaging(0.979)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CDK10

SNV

Missense_Mutation

c.184G>C

p.Asp62His

p.D62H

Q15131

protein_coding

deleterious(0.03)

benign(0.053)

TCGA-EK-A2PL-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

CDK10

SNV

Missense_Mutation

rs373968493

c.275N>A

p.Arg92His

p.R92H

Q15131

protein_coding

deleterious(0.04)

possibly_damaging(0.82)

TCGA-HG-A2PA-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unspecific

Taxol

CDK10

SNV

Missense_Mutation

novel

c.222N>C

p.Lys74Asn

p.K74N

Q15131

protein_coding

tolerated(0.26)

benign(0.013)

TCGA-HM-A4S6-01

Cervix

cervical & endocervical cancer

Female

<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
8558	CDK10	DRUGGABLE GENOME, KINASE, TRANSCRIPTION FACTOR, ENZYME, SERINE THREONINE KINASE	inhibitor	CHEMBL488436	AZD-5438
8558	CDK10	DRUGGABLE GENOME, KINASE, TRANSCRIPTION FACTOR, ENZYME, SERINE THREONINE KINASE	inhibitor	CHEMBL1230607	PHA-793887
8558	CDK10	DRUGGABLE GENOME, KINASE, TRANSCRIPTION FACTOR, ENZYME, SERINE THREONINE KINASE	inhibitor	CHEMBL3544942	RONICICLIB
8558	CDK10	DRUGGABLE GENOME, KINASE, TRANSCRIPTION FACTOR, ENZYME, SERINE THREONINE KINASE		ALVOCIDIB	ALVOCIDIB
8558	CDK10	DRUGGABLE GENOME, KINASE, TRANSCRIPTION FACTOR, ENZYME, SERINE THREONINE KINASE	inhibitor	CHEMBL445813	AT-7519

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