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: CDK11B

Gene summary for CDK11B

Gene summary.

Gene information	Species	Human
	Gene symbol	CDK11B
	Gene ID	984
	Gene name	cyclin dependent kinase 11B
	Gene Alias	CDC2L1
	Cytomap	1p36.33
	Gene Type	protein-coding
	GO ID	GO:0000278
	UniProtAcc	B7ZVY7

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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
984	CDK11B	LZE2D	Human	Esophagus	HGIN	5.78e-03	3.06e-01	0.0642
984	CDK11B	LZE4T	Human	Esophagus	ESCC	4.63e-11	3.43e-01	0.0811
984	CDK11B	LZE5T	Human	Esophagus	ESCC	1.19e-02	2.08e-01	0.0514
984	CDK11B	LZE7T	Human	Esophagus	ESCC	3.91e-14	4.63e-01	0.0667
984	CDK11B	LZE20T	Human	Esophagus	ESCC	1.90e-08	2.19e-01	0.0662
984	CDK11B	LZE22T	Human	Esophagus	ESCC	5.47e-09	3.17e-01	0.068
984	CDK11B	LZE24T	Human	Esophagus	ESCC	7.49e-13	2.76e-01	0.0596
984	CDK11B	LZE6T	Human	Esophagus	ESCC	3.37e-03	1.32e-01	0.0845
984	CDK11B	P1T-E	Human	Esophagus	ESCC	3.87e-15	5.41e-01	0.0875
984	CDK11B	P2T-E	Human	Esophagus	ESCC	3.65e-27	5.74e-01	0.1177
984	CDK11B	P4T-E	Human	Esophagus	ESCC	5.25e-38	8.97e-01	0.1323
984	CDK11B	P5T-E	Human	Esophagus	ESCC	4.90e-22	4.18e-01	0.1327
984	CDK11B	P8T-E	Human	Esophagus	ESCC	1.96e-41	7.72e-01	0.0889
984	CDK11B	P9T-E	Human	Esophagus	ESCC	3.03e-15	2.42e-01	0.1131
984	CDK11B	P10T-E	Human	Esophagus	ESCC	7.63e-29	5.11e-01	0.116
984	CDK11B	P11T-E	Human	Esophagus	ESCC	7.38e-08	3.43e-01	0.1426
984	CDK11B	P12T-E	Human	Esophagus	ESCC	1.35e-16	3.09e-01	0.1122
984	CDK11B	P15T-E	Human	Esophagus	ESCC	3.71e-16	3.67e-01	0.1149
984	CDK11B	P16T-E	Human	Esophagus	ESCC	1.68e-12	2.65e-01	0.1153
984	CDK11B	P17T-E	Human	Esophagus	ESCC	2.50e-12	3.15e-01	0.1278

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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:190331120	Esophagus	HGIN	regulation of mRNA metabolic process	91/2587	288/18723	5.06e-15	9.78e-13	91
GO:005068419	Esophagus	HGIN	regulation of mRNA processing	55/2587	137/18723	2.17e-14	3.94e-12	55
GO:000734610	Esophagus	HGIN	regulation of mitotic cell cycle	98/2587	457/18723	4.39e-06	1.42e-04	98
GO:001604919	Esophagus	HGIN	cell growth	93/2587	482/18723	4.49e-04	6.62e-03	93
GO:000155818	Esophagus	HGIN	regulation of cell growth	76/2587	414/18723	5.40e-03	4.42e-02	76
GO:1903311110	Esophagus	ESCC	regulation of mRNA metabolic process	210/8552	288/18723	3.25e-21	5.56e-19	210
GO:0050684110	Esophagus	ESCC	regulation of mRNA processing	109/8552	137/18723	3.51e-16	2.59e-14	109
GO:000734615	Esophagus	ESCC	regulation of mitotic cell cycle	293/8552	457/18723	8.00e-16	5.64e-14	293
GO:0016049110	Esophagus	ESCC	cell growth	289/8552	482/18723	1.29e-10	3.77e-09	289
GO:000155819	Esophagus	ESCC	regulation of cell growth	248/8552	414/18723	2.97e-09	6.45e-08	248
GO:190331121	Liver	HCC	regulation of mRNA metabolic process	205/7958	288/18723	3.38e-23	6.90e-21	205
GO:005068421	Liver	HCC	regulation of mRNA processing	106/7958	137/18723	7.64e-17	7.12e-15	106
GO:001604921	Liver	HCC	cell growth	269/7958	482/18723	1.84e-09	5.35e-08	269
GO:000734611	Liver	HCC	regulation of mitotic cell cycle	255/7958	457/18723	4.96e-09	1.30e-07	255
GO:000155821	Liver	HCC	regulation of cell growth	228/7958	414/18723	1.34e-07	2.55e-06	228
GO:190331118	Oral cavity	OSCC	regulation of mRNA metabolic process	197/7305	288/18723	2.83e-24	7.16e-22	197
GO:005068417	Oral cavity	OSCC	regulation of mRNA processing	104/7305	137/18723	1.32e-18	1.58e-16	104
GO:00073469	Oral cavity	OSCC	regulation of mitotic cell cycle	266/7305	457/18723	3.87e-17	3.41e-15	266
GO:001604917	Oral cavity	OSCC	cell growth	268/7305	482/18723	6.55e-14	3.51e-12	268
GO:000155816	Oral cavity	OSCC	regulation of cell growth	228/7305	414/18723	1.74e-11	6.09e-10	228

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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

CDK11B

SNV

Missense_Mutation

rs753220778

c.1543N>A

p.Val515Met

p.V515M

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-AC-A8OQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CDK11B

SNV

Missense_Mutation

c.211N>C

p.Asp71His

p.D71H

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.999)

TCGA-AR-A1AO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

CDK11B

SNV

Missense_Mutation

c.163N>A

p.Asp55Asn

p.D55N

protein_coding

deleterious_low_confidence(0.04)

possibly_damaging(0.698)

TCGA-D8-A27G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CDK11B

SNV

Missense_Mutation

novel

c.1349G>C

p.Gly450Ala

p.G450A

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-E2-A10C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

CDK11B

SNV

Missense_Mutation

c.1453G>A

p.Glu485Lys

p.E485K

protein_coding

deleterious(0)

probably_damaging(0.979)

TCGA-E9-A1NA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

CDK11B

SNV

Missense_Mutation

novel

c.2012T>C

p.Val671Ala

p.V671A

protein_coding

tolerated(0.26)

probably_damaging(0.968)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CDK11B

SNV

Missense_Mutation

c.1784N>A

p.Thr595Asn

p.T595N

protein_coding

deleterious(0)

probably_damaging(0.99)

TCGA-DS-A0VM-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CDK11B

SNV

Missense_Mutation

c.79N>C

p.Glu27Gln

p.E27Q

protein_coding

deleterious_low_confidence(0.04)

probably_damaging(0.985)

TCGA-IR-A3LA-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CDK11B

SNV

Missense_Mutation

novel

c.1399N>G

p.Lys467Glu

p.K467E

protein_coding

deleterious(0)

possibly_damaging(0.73)

TCGA-VS-A9UR-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CDK11B

SNV

Missense_Mutation

novel

c.1924N>G

p.Ser642Ala

p.S642A

protein_coding

deleterious(0.02)

probably_damaging(0.979)

TCGA-A6-2680-01

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
984	CDK11B	KINASE, DRUGGABLE GENOME, ENZYME, SERINE THREONINE KINASE	inhibitor	CHEMBL3544942	RONICICLIB
984	CDK11B	KINASE, DRUGGABLE GENOME, ENZYME, SERINE THREONINE KINASE	inhibitor	CHEMBL445813	AT-7519
984	CDK11B	KINASE, DRUGGABLE GENOME, ENZYME, SERINE THREONINE KINASE	inhibitor	CHEMBL1230607	PHA-793887
984	CDK11B	KINASE, DRUGGABLE GENOME, ENZYME, SERINE THREONINE KINASE	inhibitor	CHEMBL488436	AZD-5438

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