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: CDK17

Gene summary for CDK17

Gene summary.

Gene information	Species	Human
	Gene symbol	CDK17
	Gene ID	5128
	Gene name	cyclin dependent kinase 17
	Gene Alias	PCTAIRE2
	Cytomap	12q23.1
	Gene Type	protein-coding
	GO ID	GO:0000082
	UniProtAcc	Q00537

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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
5128	CDK17	CCI_1	Human	Cervix	CC	1.10e-03	5.77e-01	0.528
5128	CDK17	CCI_2	Human	Cervix	CC	4.43e-08	1.05e+00	0.5249
5128	CDK17	CCI_3	Human	Cervix	CC	4.74e-14	9.54e-01	0.516
5128	CDK17	AEH-subject1	Human	Endometrium	AEH	1.53e-10	3.96e-01	-0.3059
5128	CDK17	AEH-subject2	Human	Endometrium	AEH	1.42e-02	2.18e-01	-0.2525
5128	CDK17	AEH-subject4	Human	Endometrium	AEH	1.80e-10	4.18e-01	-0.2657
5128	CDK17	AEH-subject5	Human	Endometrium	AEH	1.45e-06	3.56e-01	-0.2953
5128	CDK17	EEC-subject1	Human	Endometrium	EEC	6.94e-07	3.03e-01	-0.2682
5128	CDK17	GSM6177622_NYU_UCEC3_lib1_lib1	Human	Endometrium	EEC	9.22e-03	7.31e-02	-0.1917
5128	CDK17	LZE4T	Human	Esophagus	ESCC	9.32e-07	3.32e-01	0.0811
5128	CDK17	LZE7T	Human	Esophagus	ESCC	1.93e-02	1.14e-01	0.0667
5128	CDK17	LZE8T	Human	Esophagus	ESCC	2.93e-03	4.46e-02	0.067
5128	CDK17	LZE20T	Human	Esophagus	ESCC	5.34e-04	5.35e-02	0.0662
5128	CDK17	LZE24T	Human	Esophagus	ESCC	3.10e-10	2.91e-01	0.0596
5128	CDK17	P1T-E	Human	Esophagus	ESCC	1.71e-03	2.31e-01	0.0875
5128	CDK17	P2T-E	Human	Esophagus	ESCC	1.06e-30	6.16e-01	0.1177
5128	CDK17	P4T-E	Human	Esophagus	ESCC	5.75e-14	3.15e-01	0.1323
5128	CDK17	P5T-E	Human	Esophagus	ESCC	4.18e-14	2.82e-01	0.1327
5128	CDK17	P8T-E	Human	Esophagus	ESCC	4.43e-18	3.21e-01	0.0889
5128	CDK17	P9T-E	Human	Esophagus	ESCC	1.09e-06	1.84e-01	0.1131

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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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma

∗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:00447725	Cervix	CC	mitotic cell cycle phase transition	89/2311	424/18723	2.70e-07	1.12e-05	89
GO:00000824	Cervix	CC	G1/S transition of mitotic cell cycle	49/2311	214/18723	1.16e-05	2.48e-04	49
GO:00448434	Cervix	CC	cell cycle G1/S phase transition	53/2311	241/18723	1.76e-05	3.32e-04	53
GO:00447726	Endometrium	AEH	mitotic cell cycle phase transition	67/2100	424/18723	2.37e-03	1.78e-02	67
GO:004477213	Endometrium	EEC	mitotic cell cycle phase transition	71/2168	424/18723	8.68e-04	7.97e-03	71
GO:004477216	Esophagus	ESCC	mitotic cell cycle phase transition	281/8552	424/18723	4.63e-18	4.45e-16	281
GO:000008214	Esophagus	ESCC	G1/S transition of mitotic cell cycle	134/8552	214/18723	4.04e-07	5.55e-06	134
GO:004484314	Esophagus	ESCC	cell cycle G1/S phase transition	148/8552	241/18723	5.68e-07	7.48e-06	148
GO:00447728	Oral cavity	OSCC	mitotic cell cycle phase transition	255/7305	424/18723	5.29e-19	6.98e-17	255
GO:00000826	Oral cavity	OSCC	G1/S transition of mitotic cell cycle	120/7305	214/18723	2.86e-07	4.40e-06	120
GO:00448436	Oral cavity	OSCC	cell cycle G1/S phase transition	131/7305	241/18723	8.77e-07	1.20e-05	131
GO:004477222	Oral cavity	EOLP	mitotic cell cycle phase transition	81/2218	424/18723	8.32e-06	1.59e-04	81
GO:000008221	Oral cavity	EOLP	G1/S transition of mitotic cell cycle	46/2218	214/18723	4.02e-05	5.51e-04	46
GO:004484321	Oral cavity	EOLP	cell cycle G1/S phase transition	47/2218	241/18723	3.79e-04	3.41e-03	47
GO:000008231	Oral cavity	NEOLP	G1/S transition of mitotic cell cycle	40/2005	214/18723	3.21e-04	3.11e-03	40
GO:004477231	Oral cavity	NEOLP	mitotic cell cycle phase transition	67/2005	424/18723	7.30e-04	5.98e-03	67
GO:004484331	Oral cavity	NEOLP	cell cycle G1/S phase transition	41/2005	241/18723	1.87e-03	1.28e-02	41

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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

CDK17

SNV

Missense_Mutation

c.920N>C

p.Arg307Thr

p.R307T

Q00537

protein_coding

deleterious(0)

possibly_damaging(0.732)

TCGA-A2-A0EQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

CDK17

SNV

Missense_Mutation

c.116N>G

p.Asn39Ser

p.N39S

Q00537

protein_coding

tolerated_low_confidence(0.53)

benign(0)

TCGA-A8-A075-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

epirubicin

CDK17

SNV

Missense_Mutation

c.154N>G

p.His52Asp

p.H52D

Q00537

protein_coding

tolerated_low_confidence(0.63)

benign(0.001)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CDK17

SNV

Missense_Mutation

novel

c.895C>T

p.Arg299Cys

p.R299C

Q00537

protein_coding

deleterious(0)

probably_damaging(0.944)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CDK17

SNV

Missense_Mutation

novel

c.1189G>A

p.Glu397Lys

p.E397K

Q00537

protein_coding

deleterious(0)

possibly_damaging(0.803)

TCGA-AO-A0JC-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

fluorouracil

CDK17

SNV

Missense_Mutation

rs774240202

c.935N>A

p.Arg312Gln

p.R312Q

Q00537

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-C5-A1BQ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

CDK17

SNV

Missense_Mutation

rs376992444

c.248N>G

p.Ser83Cys

p.S83C

Q00537

protein_coding

deleterious_low_confidence(0.02)

benign(0)

TCGA-C5-A7UC-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

CDK17

SNV

Missense_Mutation

c.1303N>G

p.Leu435Val

p.L435V

Q00537

protein_coding

deleterious(0.04)

benign(0.04)

TCGA-EK-A2PG-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

CDK17

SNV

Missense_Mutation

novel

c.1081C>G

p.Leu361Val

p.L361V

Q00537

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-ZJ-A8QR-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

CDK17

SNV

Missense_Mutation

novel

c.442N>T

p.Pro148Ser

p.P148S

Q00537

protein_coding

deleterious(0.03)

probably_damaging(0.967)

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
5128	CDK17	SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME, TUMOR SUPPRESSOR	inhibitor	CHEMBL1230607	PHA-793887
5128	CDK17	SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME, TUMOR SUPPRESSOR	inhibitor	CHEMBL488436	AZD-5438
5128	CDK17	SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME, TUMOR SUPPRESSOR	inhibitor	CHEMBL445813	AT-7519
5128	CDK17	SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME, TUMOR SUPPRESSOR	inhibitor	CHEMBL3544942	RONICICLIB

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