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: CDC25B

Gene summary for CDC25B

Gene summary.

Gene information	Species	Human
	Gene symbol	CDC25B
	Gene ID	994
	Gene name	cell division cycle 25B
	Gene Alias	CDC25B
	Cytomap	20p13
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	B4DIG0

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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
994	CDC25B	HTA11_1938_2000001011	Human	Colorectum	AD	2.34e-04	2.09e-01	-0.0811
994	CDC25B	HTA11_696_2000001011	Human	Colorectum	AD	1.21e-07	2.86e-01	-0.1464
994	CDC25B	HTA11_866_2000001011	Human	Colorectum	AD	9.46e-03	1.50e-01	-0.1001
994	CDC25B	HTA11_1391_2000001011	Human	Colorectum	AD	1.06e-11	4.91e-01	-0.059
994	CDC25B	HTA11_546_2000001011	Human	Colorectum	AD	1.50e-04	3.65e-01	-0.0842
994	CDC25B	HTA11_866_3004761011	Human	Colorectum	AD	4.78e-18	5.00e-01	0.096
994	CDC25B	HTA11_10711_2000001011	Human	Colorectum	AD	2.86e-03	2.07e-01	0.0338
994	CDC25B	HTA11_99999970781_79442	Human	Colorectum	MSS	4.10e-12	2.82e-01	0.294
994	CDC25B	HTA11_99999965104_69814	Human	Colorectum	MSS	2.26e-05	1.79e-01	0.281
994	CDC25B	HTA11_99999973899_84307	Human	Colorectum	MSS	2.35e-24	8.31e-01	0.2585
994	CDC25B	HTA11_99999974143_84620	Human	Colorectum	MSS	3.35e-22	5.38e-01	0.3005
994	CDC25B	LZE2T	Human	Esophagus	ESCC	9.51e-04	3.12e-01	0.082
994	CDC25B	LZE4T	Human	Esophagus	ESCC	9.36e-14	7.82e-02	0.0811
994	CDC25B	LZE8T	Human	Esophagus	ESCC	4.41e-03	3.55e-02	0.067
994	CDC25B	P1T-E	Human	Esophagus	ESCC	2.11e-04	3.71e-01	0.0875
994	CDC25B	P2T-E	Human	Esophagus	ESCC	3.87e-09	4.98e-01	0.1177
994	CDC25B	P4T-E	Human	Esophagus	ESCC	3.82e-10	3.75e-01	0.1323
994	CDC25B	P5T-E	Human	Esophagus	ESCC	7.62e-16	1.77e-01	0.1327
994	CDC25B	P8T-E	Human	Esophagus	ESCC	2.29e-02	1.43e-02	0.0889
994	CDC25B	P9T-E	Human	Esophagus	ESCC	1.50e-06	2.54e-01	0.1131

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:0016311	Colorectum	AD	dephosphorylation	123/3918	417/18723	1.84e-05	3.82e-04	123
GO:0006470	Colorectum	AD	protein dephosphorylation	88/3918	281/18723	2.56e-05	4.89e-04	88
GO:0000910	Colorectum	AD	cytokinesis	59/3918	173/18723	3.74e-05	6.75e-04	59
GO:0033674	Colorectum	AD	positive regulation of kinase activity	131/3918	467/18723	1.28e-04	1.85e-03	131
GO:0045860	Colorectum	AD	positive regulation of protein kinase activity	107/3918	386/18723	8.01e-04	7.92e-03	107
GO:0007346	Colorectum	AD	regulation of mitotic cell cycle	119/3918	457/18723	4.60e-03	3.14e-02	119
GO:0045787	Colorectum	AD	positive regulation of cell cycle	85/3918	313/18723	4.76e-03	3.22e-02	85
GO:0045931	Colorectum	AD	positive regulation of mitotic cell cycle	37/3918	121/18723	7.88e-03	4.73e-02	37
GO:00336742	Colorectum	MSS	positive regulation of kinase activity	122/3467	467/18723	2.50e-05	5.21e-04	122
GO:00458602	Colorectum	MSS	positive regulation of protein kinase activity	102/3467	386/18723	6.93e-05	1.20e-03	102
GO:00009102	Colorectum	MSS	cytokinesis	49/3467	173/18723	1.02e-03	1.02e-02	49
GO:00457871	Colorectum	MSS	positive regulation of cell cycle	80/3467	313/18723	1.15e-03	1.12e-02	80
GO:00064702	Colorectum	MSS	protein dephosphorylation	73/3467	281/18723	1.15e-03	1.12e-02	73
GO:00163112	Colorectum	MSS	dephosphorylation	101/3467	417/18723	1.98e-03	1.70e-02	101
GO:00073461	Colorectum	MSS	regulation of mitotic cell cycle	108/3467	457/18723	3.30e-03	2.50e-02	108
GO:0090068	Colorectum	MSS	positive regulation of cell cycle process	60/3467	236/18723	5.01e-03	3.46e-02	60
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:00482853	Esophagus	ESCC	organelle fission	301/8552	488/18723	4.64e-13	2.12e-11	301
GO:00002802	Esophagus	ESCC	nuclear division	270/8552	439/18723	1.17e-11	4.24e-10	270

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0411023	Esophagus	ESCC	Cell cycle	126/4205	157/8465	1.34e-15	5.60e-14	2.87e-14	126
hsa0411033	Esophagus	ESCC	Cell cycle	126/4205	157/8465	1.34e-15	5.60e-14	2.87e-14	126
hsa041102	Liver	HCC	Cell cycle	106/4020	157/8465	2.54e-07	3.04e-06	1.69e-06	106
hsa041103	Liver	HCC	Cell cycle	106/4020	157/8465	2.54e-07	3.04e-06	1.69e-06	106
hsa041108	Oral cavity	OSCC	Cell cycle	118/3704	157/8465	7.15e-16	2.66e-14	1.35e-14	118
hsa0401014	Oral cavity	OSCC	MAPK signaling pathway	165/3704	302/8465	7.11e-05	2.74e-04	1.40e-04	165
hsa0411015	Oral cavity	OSCC	Cell cycle	118/3704	157/8465	7.15e-16	2.66e-14	1.35e-14	118
hsa0401015	Oral cavity	OSCC	MAPK signaling pathway	165/3704	302/8465	7.11e-05	2.74e-04	1.40e-04	165

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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

CDC25B

SNV

Missense_Mutation

c.1293C>G

p.Ile431Met

p.I431M

P30305

protein_coding

tolerated(0.05)

benign(0.04)

TCGA-A2-A0YH-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

CDC25B

SNV

Missense_Mutation

c.1634T>C

p.Met545Thr

p.M545T

P30305

protein_coding

deleterious(0)

probably_damaging(0.995)

TCGA-A8-A081-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CDC25B

SNV

Missense_Mutation

novel

c.275N>A

p.Arg92Gln

p.R92Q

P30305

protein_coding

deleterious(0.04)

possibly_damaging(0.652)

TCGA-AC-A62V-01

Breast

breast invasive carcinoma

Male

<65

III/IV

Targeted Molecular therapy

denosumab

CDC25B

SNV

Missense_Mutation

c.1055N>A

p.Arg352Gln

p.R352Q

P30305

protein_coding

deleterious(0.01)

benign(0.254)

TCGA-BH-A0EE-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

docetaxel

CDC25B

insertion

In_Frame_Ins

novel

c.401_402insCTCCCTGTCGTCTGA

p.Ala134_Ala135insSerLeuSerSerGlu

p.A134_A135insSLSSE

P30305

protein_coding

TCGA-A8-A08S-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

CDC25B

deletion

Frame_Shift_Del

novel

c.589_590delNN

p.Phe197CysfsTer43

p.F197Cfs*43

P30305

protein_coding

TCGA-AR-A2LH-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

CDC25B

SNV

Missense_Mutation

rs767534464

c.659N>A

p.Arg220His

p.R220H

P30305

protein_coding

tolerated(0.13)

probably_damaging(0.919)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CDC25B

SNV

Missense_Mutation

rs770335566

c.1169N>A

p.Arg390Gln

p.R390Q

P30305

protein_coding

deleterious(0.04)

possibly_damaging(0.711)

TCGA-C5-A1MN-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

CDC25B

SNV

Missense_Mutation

c.1072N>A

p.Glu358Lys

p.E358K

P30305

protein_coding

tolerated(0.15)

benign(0.403)

TCGA-FU-A3WB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CDC25B

SNV

Missense_Mutation

novel

c.1489N>G

p.Met497Val

p.M497V

P30305

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-5M-AAT6-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

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
994	CDC25B	DRUGGABLE GENOME, PROTEIN PHOSPHATASE, KINASE		Avastin+/-Tarceva
994	CDC25B	DRUGGABLE GENOME, PROTEIN PHOSPHATASE, KINASE		NSC-663284	CHEMBL337173	25703307
994	CDC25B	DRUGGABLE GENOME, PROTEIN PHOSPHATASE, KINASE		NSC-156744	CHEMBL1481453	22524450
994	CDC25B	DRUGGABLE GENOME, PROTEIN PHOSPHATASE, KINASE		NSC-125252	CHEMBL1408031	22524450
994	CDC25B	DRUGGABLE GENOME, PROTEIN PHOSPHATASE, KINASE		NSC-109483	CHEMBL507159	22524450
994	CDC25B	DRUGGABLE GENOME, PROTEIN PHOSPHATASE, KINASE		NSC-122400	CHEMBL2059067	22524450
994	CDC25B	DRUGGABLE GENOME, PROTEIN PHOSPHATASE, KINASE		NSC-46080	CHEMBL1331754	22524450
994	CDC25B	DRUGGABLE GENOME, PROTEIN PHOSPHATASE, KINASE		NSC-601364	CHEMBL1270061	22524450
994	CDC25B	DRUGGABLE GENOME, PROTEIN PHOSPHATASE, KINASE		NSC-119915	CHEMBL1481974	22524450
994	CDC25B	DRUGGABLE GENOME, PROTEIN PHOSPHATASE, KINASE		NSC-127133	CHEMBL1172911	22524450

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