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: CDC16

Gene summary for CDC16

Gene summary.

Gene information	Species	Human
	Gene symbol	CDC16
	Gene ID	8881
	Gene name	cell division cycle 16
	Gene Alias	ANAPC6
	Cytomap	13q34
	Gene Type	protein-coding
	GO ID	GO:0000070
	UniProtAcc	A0A024RDZ2

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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
8881	CDC16	HTA11_347_2000001011	Human	Colorectum	AD	8.93e-05	2.81e-01	-0.1954
8881	CDC16	HTA11_99999965104_69814	Human	Colorectum	MSS	7.09e-09	6.53e-01	0.281
8881	CDC16	HTA11_99999971662_82457	Human	Colorectum	MSS	1.35e-07	5.21e-01	0.3859
8881	CDC16	A015-C-203	Human	Colorectum	FAP	3.41e-09	-1.39e-01	-0.1294
8881	CDC16	A001-C-108	Human	Colorectum	FAP	2.45e-04	-1.13e-01	-0.0272
8881	CDC16	A002-C-205	Human	Colorectum	FAP	2.46e-02	-1.62e-01	-0.1236
8881	CDC16	A015-C-106	Human	Colorectum	FAP	4.12e-03	-9.97e-02	-0.0511
8881	CDC16	A002-C-114	Human	Colorectum	FAP	4.73e-02	-1.43e-01	-0.1561
8881	CDC16	A015-C-104	Human	Colorectum	FAP	2.55e-10	-1.05e-01	-0.1899
8881	CDC16	A001-C-014	Human	Colorectum	FAP	1.04e-03	-9.97e-02	0.0135
8881	CDC16	A002-C-016	Human	Colorectum	FAP	7.40e-05	-1.80e-01	0.0521
8881	CDC16	A002-C-116	Human	Colorectum	FAP	2.70e-10	-1.37e-01	-0.0452
8881	CDC16	A018-E-020	Human	Colorectum	FAP	2.50e-02	-1.94e-01	-0.2034
8881	CDC16	F034	Human	Colorectum	FAP	4.01e-07	-1.09e-01	-0.0665
8881	CDC16	CRC-1-8810	Human	Colorectum	CRC	2.17e-07	3.36e-01	0.6257
8881	CDC16	LZE7T	Human	Esophagus	ESCC	3.14e-04	1.38e-01	0.0667
8881	CDC16	LZE8T	Human	Esophagus	ESCC	6.64e-05	5.63e-02	0.067
8881	CDC16	LZE24T	Human	Esophagus	ESCC	4.45e-07	1.87e-01	0.0596
8881	CDC16	P1T-E	Human	Esophagus	ESCC	2.60e-04	2.37e-01	0.0875
8881	CDC16	P2T-E	Human	Esophagus	ESCC	9.70e-17	3.01e-01	0.1177

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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:0010498	Colorectum	AD	proteasomal protein catabolic process	174/3918	490/18723	3.18e-14	7.66e-12	174
GO:0043161	Colorectum	AD	proteasome-mediated ubiquitin-dependent protein catabolic process	141/3918	412/18723	1.77e-10	1.68e-08	141
GO:0000209	Colorectum	AD	protein polyubiquitination	78/3918	236/18723	8.71e-06	2.06e-04	78
GO:0033044	Colorectum	AD	regulation of chromosome organization	60/3918	187/18723	2.25e-04	2.94e-03	60
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:0045842	Colorectum	AD	positive regulation of mitotic metaphase/anaphase transition	8/3918	15/18723	5.67e-03	3.64e-02	8
GO:1901970	Colorectum	AD	positive regulation of mitotic sister chromatid separation	8/3918	15/18723	5.67e-03	3.64e-02	8
GO:1905820	Colorectum	AD	positive regulation of chromosome separation	9/3918	18/18723	5.82e-03	3.67e-02	9
GO:0140014	Colorectum	AD	mitotic nuclear division	78/3918	287/18723	6.48e-03	4.05e-02	78
GO:0045931	Colorectum	AD	positive regulation of mitotic cell cycle	37/3918	121/18723	7.88e-03	4.73e-02	37
GO:00104982	Colorectum	MSS	proteasomal protein catabolic process	157/3467	490/18723	2.39e-13	5.25e-11	157
GO:00431612	Colorectum	MSS	proteasome-mediated ubiquitin-dependent protein catabolic process	127/3467	412/18723	7.70e-10	6.32e-08	127
GO:00002092	Colorectum	MSS	protein polyubiquitination	72/3467	236/18723	5.19e-06	1.42e-04	72
GO:00330441	Colorectum	MSS	regulation of chromosome organization	55/3467	187/18723	1.86e-04	2.63e-03	55
GO:00457871	Colorectum	MSS	positive regulation of cell cycle	80/3467	313/18723	1.15e-03	1.12e-02	80
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:01400141	Colorectum	MSS	mitotic nuclear division	70/3467	287/18723	7.48e-03	4.72e-02	70
GO:00431614	Colorectum	FAP	proteasome-mediated ubiquitin-dependent protein catabolic process	98/2622	412/18723	5.41e-08	4.20e-06	98

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa04120	Colorectum	AD	Ubiquitin mediated proteolysis	58/2092	142/8465	1.46e-05	1.53e-04	9.76e-05	58
hsa05166	Colorectum	AD	Human T-cell leukemia virus 1 infection	72/2092	222/8465	5.24e-03	2.44e-02	1.55e-02	72
hsa041201	Colorectum	AD	Ubiquitin mediated proteolysis	58/2092	142/8465	1.46e-05	1.53e-04	9.76e-05	58
hsa051661	Colorectum	AD	Human T-cell leukemia virus 1 infection	72/2092	222/8465	5.24e-03	2.44e-02	1.55e-02	72
hsa041204	Colorectum	MSS	Ubiquitin mediated proteolysis	55/1875	142/8465	5.02e-06	6.00e-05	3.68e-05	55
hsa051662	Colorectum	MSS	Human T-cell leukemia virus 1 infection	68/1875	222/8465	1.84e-03	9.61e-03	5.89e-03	68
hsa041205	Colorectum	MSS	Ubiquitin mediated proteolysis	55/1875	142/8465	5.02e-06	6.00e-05	3.68e-05	55
hsa051663	Colorectum	MSS	Human T-cell leukemia virus 1 infection	68/1875	222/8465	1.84e-03	9.61e-03	5.89e-03	68
hsa041206	Colorectum	FAP	Ubiquitin mediated proteolysis	51/1404	142/8465	1.55e-08	5.84e-07	3.55e-07	51
hsa04110	Colorectum	FAP	Cell cycle	37/1404	157/8465	1.44e-02	4.77e-02	2.90e-02	37
hsa041207	Colorectum	FAP	Ubiquitin mediated proteolysis	51/1404	142/8465	1.55e-08	5.84e-07	3.55e-07	51
hsa041101	Colorectum	FAP	Cell cycle	37/1404	157/8465	1.44e-02	4.77e-02	2.90e-02	37
hsa041208	Colorectum	CRC	Ubiquitin mediated proteolysis	42/1091	142/8465	9.98e-08	6.67e-06	4.52e-06	42
hsa041209	Colorectum	CRC	Ubiquitin mediated proteolysis	42/1091	142/8465	9.98e-08	6.67e-06	4.52e-06	42
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

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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

CDC16

SNV

Missense_Mutation

novel

c.1410G>C

p.Gln470His

p.Q470H

Q13042

protein_coding

tolerated(0.06)

probably_damaging(0.967)

TCGA-A8-A06X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CDC16

SNV

Missense_Mutation

novel

c.1828N>C

p.Met610Leu

p.M610L

Q13042

protein_coding

deleterious_low_confidence(0)

benign(0.354)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CDC16

SNV

Missense_Mutation

novel

c.79N>C

p.Asp27His

p.D27H

Q13042

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-BH-A2L8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

CDC16

insertion

In_Frame_Ins

novel

c.1050_1051insTTTGGGAGGCCGAGACAGGCAGATTACCTTAGGTCA

p.His350_Asp351insPheGlyArgProArgGlnAlaAspTyrLeuArgSer

p.H350_D351insFGRPRQADYLRS

Q13042

protein_coding

TCGA-A2-A0EO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

CDC16

insertion

Frame_Shift_Ins

novel

c.1737_1738insGTTTATGT

p.Leu580ValfsTer28

p.L580Vfs*28

Q13042

protein_coding

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

CDC16

insertion

Frame_Shift_Ins

novel

c.1738_1739insGAATGATTGTACCTAATACATCTGTTCAGATCTG

p.Leu580ArgfsTer33

p.L580Rfs*33

Q13042

protein_coding

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

CDC16

SNV

Missense_Mutation

c.1685C>T

p.Pro562Leu

p.P562L

Q13042

protein_coding

deleterious_low_confidence(0.02)

benign(0.015)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CDC16

insertion

Frame_Shift_Ins

novel

c.1363dupT

p.Cys455LeufsTer5

p.C455Lfs*5

Q13042

protein_coding

TCGA-VS-A9V4-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CDC16

SNV

Missense_Mutation

c.1739T>G

p.Leu580Arg

p.L580R

Q13042

protein_coding

deleterious_low_confidence(0.01)

benign(0.085)

TCGA-A6-6780-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

CDC16

SNV

Missense_Mutation

rs373980044

c.1859C>T

p.Thr620Met

p.T620M

Q13042

protein_coding

deleterious_low_confidence(0)

benign(0.416)

TCGA-A6-6781-01

Colorectum

colon adenocarcinoma

Male

<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

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