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: CCNK

Gene summary for CCNK

Gene summary.

Gene information	Species	Human
	Gene symbol	CCNK
	Gene ID	8812
	Gene name	cyclin K
	Gene Alias	CPR4
	Cytomap	14q32.2
	Gene Type	protein-coding
	GO ID	GO:0000079
	UniProtAcc	A0A024R6K1

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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
8812	CCNK	LZE2D	Human	Esophagus	HGIN	2.39e-02	2.72e-01	0.0642
8812	CCNK	LZE2T	Human	Esophagus	ESCC	2.77e-03	8.05e-01	0.082
8812	CCNK	LZE4T	Human	Esophagus	ESCC	9.30e-20	5.90e-01	0.0811
8812	CCNK	LZE5T	Human	Esophagus	ESCC	1.14e-04	5.76e-01	0.0514
8812	CCNK	LZE7T	Human	Esophagus	ESCC	6.56e-06	2.39e-01	0.0667
8812	CCNK	LZE8T	Human	Esophagus	ESCC	8.98e-09	1.96e-01	0.067
8812	CCNK	LZE20T	Human	Esophagus	ESCC	1.48e-20	5.89e-01	0.0662
8812	CCNK	LZE22D1	Human	Esophagus	HGIN	4.39e-03	2.13e-02	0.0595
8812	CCNK	LZE22T	Human	Esophagus	ESCC	3.92e-07	3.78e-01	0.068
8812	CCNK	LZE24T	Human	Esophagus	ESCC	2.07e-41	1.18e+00	0.0596
8812	CCNK	LZE6T	Human	Esophagus	ESCC	3.58e-07	1.06e-01	0.0845
8812	CCNK	P1T-E	Human	Esophagus	ESCC	2.81e-16	6.15e-01	0.0875
8812	CCNK	P2T-E	Human	Esophagus	ESCC	5.00e-27	3.90e-01	0.1177
8812	CCNK	P4T-E	Human	Esophagus	ESCC	1.45e-22	5.76e-01	0.1323
8812	CCNK	P5T-E	Human	Esophagus	ESCC	1.73e-17	3.82e-01	0.1327
8812	CCNK	P8T-E	Human	Esophagus	ESCC	3.89e-25	5.52e-01	0.0889
8812	CCNK	P9T-E	Human	Esophagus	ESCC	7.44e-17	3.08e-01	0.1131
8812	CCNK	P10T-E	Human	Esophagus	ESCC	7.91e-44	7.47e-01	0.116
8812	CCNK	P11T-E	Human	Esophagus	ESCC	1.36e-13	4.92e-01	0.1426
8812	CCNK	P12T-E	Human	Esophagus	ESCC	5.11e-47	8.58e-01	0.1122

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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
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:004578710	Esophagus	ESCC	positive regulation of cell cycle	196/8552	313/18723	9.27e-10	2.24e-08	196
GO:003278412	Esophagus	ESCC	regulation of DNA-templated transcription, elongation	45/8552	53/18723	3.64e-09	7.61e-08	45
GO:19040294	Esophagus	ESCC	regulation of cyclin-dependent protein kinase activity	69/8552	98/18723	6.04e-07	7.91e-06	69
GO:00000794	Esophagus	ESCC	regulation of cyclin-dependent protein serine/threonine kinase activity	66/8552	94/18723	1.24e-06	1.53e-05	66
GO:00719029	Esophagus	ESCC	positive regulation of protein serine/threonine kinase activity	124/8552	200/18723	2.27e-06	2.61e-05	124
GO:003278613	Esophagus	ESCC	positive regulation of DNA-templated transcription, elongation	24/8552	27/18723	3.48e-06	3.84e-05	24
GO:004586018	Esophagus	ESCC	positive regulation of protein kinase activity	219/8552	386/18723	6.91e-06	6.97e-05	219
GO:003367420	Esophagus	ESCC	positive regulation of kinase activity	260/8552	467/18723	7.26e-06	7.22e-05	260
GO:005185115	Esophagus	ESCC	modulation by host of symbiont process	43/8552	60/18723	4.00e-05	3.22e-04	43
GO:00708161	Esophagus	ESCC	phosphorylation of RNA polymerase II C-terminal domain	12/8552	12/18723	8.21e-05	6.01e-04	12
GO:19040312	Esophagus	ESCC	positive regulation of cyclin-dependent protein kinase activity	26/8552	33/18723	1.06e-04	7.43e-04	26
GO:005181714	Esophagus	ESCC	modulation of process of other organism involved in symbiotic interaction	54/8552	81/18723	1.09e-04	7.64e-04	54
GO:00457372	Esophagus	ESCC	positive regulation of cyclin-dependent protein serine/threonine kinase activity	23/8552	29/18723	2.25e-04	1.40e-03	23
GO:003582114	Esophagus	ESCC	modulation of process of other organism	64/8552	106/18723	1.61e-03	7.50e-03	64
GO:004478815	Esophagus	ESCC	modulation by host of viral process	22/8552	30/18723	1.98e-03	8.90e-03	22
GO:005170214	Esophagus	ESCC	biological process involved in interaction with symbiont	57/8552	94/18723	2.46e-03	1.07e-02	57
GO:004482714	Esophagus	ESCC	modulation by host of viral genome replication	14/8552	19/18723	1.27e-02	4.21e-02	14
GO:001603212	Liver	Cirrhotic	viral process	203/4634	415/18723	5.40e-27	3.76e-24	203
GO:001905812	Liver	Cirrhotic	viral life cycle	148/4634	317/18723	1.12e-17	1.64e-15	148
GO:004440312	Liver	Cirrhotic	biological process involved in symbiotic interaction	131/4634	290/18723	2.00e-14	1.84e-12	131

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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

CCNK

SNV

Missense_Mutation

rs867757117

c.1360G>A

p.Glu454Lys

p.E454K

O75909

protein_coding

deleterious_low_confidence(0)

benign(0)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

CCNK

SNV

Missense_Mutation

novel

c.986N>A

p.Ser329Tyr

p.S329Y

O75909

protein_coding

deleterious(0)

benign(0.054)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CCNK

SNV

Missense_Mutation

c.656N>G

p.Lys219Arg

p.K219R

O75909

protein_coding

deleterious(0.04)

benign(0.348)

TCGA-E2-A15L-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

CCNK

deletion

Frame_Shift_Del

c.209delN

p.Leu71TrpfsTer5

p.L71Wfs*5

O75909

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

CCNK

deletion

Frame_Shift_Del

novel

c.806delN

p.His271IlefsTer112

p.H271Ifs*112

O75909

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

CCNK

SNV

Missense_Mutation

c.1298N>G

p.Ser433Cys

p.S433C

O75909

protein_coding

deleterious_low_confidence(0)

benign(0.339)

TCGA-EK-A2RC-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

CCNK

SNV

Missense_Mutation

novel

c.149N>C

p.Arg50Pro

p.R50P

O75909

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-VS-A9V1-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CCNK

SNV

Missense_Mutation

novel

c.206N>T

p.Asp69Val

p.D69V

O75909

protein_coding

tolerated(0.4)

possibly_damaging(0.584)

TCGA-AA-3950-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

CCNK

SNV

Missense_Mutation

c.568N>G

p.Asn190Asp

p.N190D

O75909

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-G4-6588-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

CCNK

SNV

Missense_Mutation

c.1606N>G

p.Pro536Ala

p.P536A

O75909

protein_coding

deleterious_low_confidence(0.01)

benign(0.283)

TCGA-NH-A6GB-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Chemotherapy

oxaliplatin

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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
8812	CCNK	KINASE		fluorouracil	FLUOROURACIL
8812	CCNK	KINASE		epirubicin	EPIRUBICIN
8812	CCNK	KINASE		cyclophosphamide	CYCLOPHOSPHAMIDE

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