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: CDC27

Gene summary for CDC27

Gene summary.

Gene information	Species	Human
	Gene symbol	CDC27
	Gene ID	996
	Gene name	cell division cycle 27
	Gene Alias	ANAPC3
	Cytomap	17q21.32
	Gene Type	protein-coding
	GO ID	GO:0000070
	UniProtAcc	P30260

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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
996	CDC27	LZE4T	Human	Esophagus	ESCC	5.71e-12	5.02e-01	0.0811
996	CDC27	LZE7T	Human	Esophagus	ESCC	6.61e-06	4.22e-01	0.0667
996	CDC27	LZE8T	Human	Esophagus	ESCC	4.22e-07	2.24e-01	0.067
996	CDC27	LZE20T	Human	Esophagus	ESCC	1.95e-05	7.29e-02	0.0662
996	CDC27	LZE24T	Human	Esophagus	ESCC	3.42e-09	2.90e-01	0.0596
996	CDC27	P2T-E	Human	Esophagus	ESCC	6.74e-16	4.12e-01	0.1177
996	CDC27	P4T-E	Human	Esophagus	ESCC	2.29e-19	4.71e-01	0.1323
996	CDC27	P5T-E	Human	Esophagus	ESCC	3.40e-20	4.17e-01	0.1327
996	CDC27	P8T-E	Human	Esophagus	ESCC	9.90e-24	4.06e-01	0.0889
996	CDC27	P9T-E	Human	Esophagus	ESCC	3.29e-08	1.95e-01	0.1131
996	CDC27	P10T-E	Human	Esophagus	ESCC	3.70e-20	8.74e-02	0.116
996	CDC27	P11T-E	Human	Esophagus	ESCC	2.12e-14	5.60e-01	0.1426
996	CDC27	P12T-E	Human	Esophagus	ESCC	1.37e-14	2.92e-01	0.1122
996	CDC27	P15T-E	Human	Esophagus	ESCC	3.03e-10	2.87e-01	0.1149
996	CDC27	P16T-E	Human	Esophagus	ESCC	6.97e-19	2.58e-01	0.1153
996	CDC27	P17T-E	Human	Esophagus	ESCC	2.35e-03	2.74e-01	0.1278
996	CDC27	P19T-E	Human	Esophagus	ESCC	2.00e-05	8.06e-01	0.1662
996	CDC27	P20T-E	Human	Esophagus	ESCC	7.27e-11	3.29e-01	0.1124
996	CDC27	P21T-E	Human	Esophagus	ESCC	5.95e-36	6.69e-01	0.1617
996	CDC27	P22T-E	Human	Esophagus	ESCC	7.03e-19	4.07e-01	0.1236

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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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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:0010498111	Esophagus	ESCC	proteasomal protein catabolic process	369/8552	490/18723	1.13e-41	1.80e-38	369
GO:0043161111	Esophagus	ESCC	proteasome-mediated ubiquitin-dependent protein catabolic process	312/8552	412/18723	3.53e-36	4.48e-33	312
GO:014001414	Esophagus	ESCC	mitotic nuclear division	218/8552	287/18723	6.17e-26	1.78e-23	218
GO:000007011	Esophagus	ESCC	mitotic sister chromatid segregation	138/8552	168/18723	1.37e-22	2.63e-20	138
GO:00008194	Esophagus	ESCC	sister chromatid segregation	157/8552	202/18723	8.41e-21	1.33e-18	157
GO:003304416	Esophagus	ESCC	regulation of chromosome organization	145/8552	187/18723	3.80e-19	4.31e-17	145
GO:000705911	Esophagus	ESCC	chromosome segregation	238/8552	346/18723	1.72e-18	1.82e-16	238
GO:004477216	Esophagus	ESCC	mitotic cell cycle phase transition	281/8552	424/18723	4.63e-18	4.45e-16	281
GO:000020917	Esophagus	ESCC	protein polyubiquitination	170/8552	236/18723	1.40e-16	1.09e-14	170
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:00988133	Esophagus	ESCC	nuclear chromosome segregation	187/8552	281/18723	1.00e-12	4.36e-11	187
GO:00002802	Esophagus	ESCC	nuclear division	270/8552	439/18723	1.17e-11	4.24e-10	270
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:004578710	Esophagus	ESCC	positive regulation of cell cycle	196/8552	313/18723	9.27e-10	2.24e-08	196
GO:00519833	Esophagus	ESCC	regulation of chromosome segregation	67/8552	91/18723	5.42e-08	9.66e-07	67
GO:00070883	Esophagus	ESCC	regulation of mitotic nuclear division	78/8552	110/18723	6.96e-08	1.21e-06	78
GO:00070912	Esophagus	ESCC	metaphase/anaphase transition of mitotic cell cycle	49/8552	62/18723	7.65e-08	1.33e-06	49
GO:007097912	Esophagus	ESCC	protein K11-linked ubiquitination	27/8552	29/18723	8.09e-08	1.39e-06	27

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0412027	Esophagus	ESCC	Ubiquitin mediated proteolysis	122/4205	142/8465	6.53e-20	7.29e-18	3.74e-18	122
hsa0411023	Esophagus	ESCC	Cell cycle	126/4205	157/8465	1.34e-15	5.60e-14	2.87e-14	126
hsa05166211	Esophagus	ESCC	Human T-cell leukemia virus 1 infection	164/4205	222/8465	8.13e-14	2.09e-12	1.07e-12	164
hsa041146	Esophagus	ESCC	Oocyte meiosis	77/4205	131/8465	2.19e-02	4.80e-02	2.46e-02	77
hsa0412036	Esophagus	ESCC	Ubiquitin mediated proteolysis	122/4205	142/8465	6.53e-20	7.29e-18	3.74e-18	122
hsa0411033	Esophagus	ESCC	Cell cycle	126/4205	157/8465	1.34e-15	5.60e-14	2.87e-14	126
hsa05166310	Esophagus	ESCC	Human T-cell leukemia virus 1 infection	164/4205	222/8465	8.13e-14	2.09e-12	1.07e-12	164
hsa0411411	Esophagus	ESCC	Oocyte meiosis	77/4205	131/8465	2.19e-02	4.80e-02	2.46e-02	77
hsa0412041	Liver	HCC	Ubiquitin mediated proteolysis	110/4020	142/8465	1.67e-13	3.74e-12	2.08e-12	110
hsa041102	Liver	HCC	Cell cycle	106/4020	157/8465	2.54e-07	3.04e-06	1.69e-06	106
hsa0516622	Liver	HCC	Human T-cell leukemia virus 1 infection	139/4020	222/8465	3.17e-06	2.79e-05	1.55e-05	139
hsa0412051	Liver	HCC	Ubiquitin mediated proteolysis	110/4020	142/8465	1.67e-13	3.74e-12	2.08e-12	110
hsa041103	Liver	HCC	Cell cycle	106/4020	157/8465	2.54e-07	3.04e-06	1.69e-06	106
hsa0516632	Liver	HCC	Human T-cell leukemia virus 1 infection	139/4020	222/8465	3.17e-06	2.79e-05	1.55e-05	139
hsa0412012	Lung	IAC	Ubiquitin mediated proteolysis	40/1053	142/8465	3.24e-07	1.76e-05	1.17e-05	40
hsa0516616	Lung	IAC	Human T-cell leukemia virus 1 infection	49/1053	222/8465	3.44e-05	6.38e-04	4.24e-04	49
hsa041105	Lung	IAC	Cell cycle	30/1053	157/8465	1.03e-02	3.83e-02	2.54e-02	30
hsa0412013	Lung	IAC	Ubiquitin mediated proteolysis	40/1053	142/8465	3.24e-07	1.76e-05	1.17e-05	40
hsa0516617	Lung	IAC	Human T-cell leukemia virus 1 infection	49/1053	222/8465	3.44e-05	6.38e-04	4.24e-04	49
hsa0411012	Lung	IAC	Cell cycle	30/1053	157/8465	1.03e-02	3.83e-02	2.54e-02	30

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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

CDC27

SNV

Missense_Mutation

novel

c.1178N>A

p.Ser393Tyr

p.S393Y

P30260

protein_coding

tolerated(0.13)

benign(0.038)

TCGA-A2-A0YL-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

CDC27

SNV

Missense_Mutation

rs745491637

c.388N>T

p.Arg130Trp

p.R130W

P30260

protein_coding

deleterious(0)

probably_damaging(0.995)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CDC27

SNV

Missense_Mutation

rs79201963

c.1549N>A

p.Glu517Lys

p.E517K

P30260

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-BH-A0E7-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

CDC27

SNV

Missense_Mutation

novel

c.1819N>A

p.Ala607Thr

p.A607T

P30260

protein_coding

tolerated(0.3)

possibly_damaging(0.496)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CDC27

SNV

Missense_Mutation

c.284N>T

p.Gly95Val

p.G95V

P30260

protein_coding

deleterious(0.01)

benign(0.311)

TCGA-DS-A0VM-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CDC27

SNV

Missense_Mutation

rs776145016

c.1902N>G

p.Ile634Met

p.I634M

P30260

protein_coding

deleterious(0.05)

probably_damaging(0.977)

TCGA-EK-A2PG-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

CDC27

SNV

Missense_Mutation

novel

c.2272C>G

p.Gln758Glu

p.Q758E

P30260

protein_coding

tolerated(0.14)

benign(0.175)

TCGA-VS-A9UZ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

CDC27

deletion

Frame_Shift_Del

novel

c.2330_2349delNNNNNNNNNNNNNNNNNNNN

p.Ala777GlyfsTer3

p.A777Gfs*3

P30260

protein_coding

TCGA-C5-A8XH-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

CDC27

SNV

Missense_Mutation

c.2362N>T

p.Arg788Cys

p.R788C

P30260

protein_coding

deleterious(0.03)

probably_damaging(0.925)

TCGA-AA-3864-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

CDC27

SNV

Missense_Mutation

c.2306N>T

p.Ala769Val

p.A769V

P30260

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AA-3864-01

Colorectum

colon adenocarcinoma

Male

>=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

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