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: ANAPC5

Gene summary for ANAPC5

Gene summary.

Gene information	Species	Human
	Gene symbol	ANAPC5
	Gene ID	51433
	Gene name	anaphase promoting complex subunit 5
	Gene Alias	APC5
	Cytomap	12q24.31
	Gene Type	protein-coding
	GO ID	GO:0000070
	UniProtAcc	Q9UJX4

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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
51433	ANAPC5	HTA11_1938_2000001011	Human	Colorectum	AD	1.19e-02	3.96e-01	-0.0811
51433	ANAPC5	HTA11_347_2000001011	Human	Colorectum	AD	5.66e-07	4.73e-01	-0.1954
51433	ANAPC5	HTA11_99999965062_69753	Human	Colorectum	MSI-H	1.43e-04	9.39e-01	0.3487
51433	ANAPC5	A015-C-203	Human	Colorectum	FAP	1.49e-25	-2.75e-01	-0.1294
51433	ANAPC5	A015-C-204	Human	Colorectum	FAP	3.48e-03	-2.82e-01	-0.0228
51433	ANAPC5	A014-C-040	Human	Colorectum	FAP	4.74e-03	-3.69e-01	-0.1184
51433	ANAPC5	A002-C-201	Human	Colorectum	FAP	8.30e-09	-2.48e-01	0.0324
51433	ANAPC5	A002-C-203	Human	Colorectum	FAP	4.73e-04	-8.24e-02	0.2786
51433	ANAPC5	A001-C-119	Human	Colorectum	FAP	4.44e-06	-2.81e-01	-0.1557
51433	ANAPC5	A001-C-108	Human	Colorectum	FAP	3.85e-12	-1.77e-01	-0.0272
51433	ANAPC5	A002-C-205	Human	Colorectum	FAP	5.65e-17	-3.06e-01	-0.1236
51433	ANAPC5	A001-C-104	Human	Colorectum	FAP	7.91e-03	-9.38e-02	0.0184
51433	ANAPC5	A015-C-006	Human	Colorectum	FAP	3.29e-10	-2.43e-01	-0.0994
51433	ANAPC5	A015-C-106	Human	Colorectum	FAP	1.36e-09	-1.07e-01	-0.0511
51433	ANAPC5	A002-C-114	Human	Colorectum	FAP	1.58e-13	-3.04e-01	-0.1561
51433	ANAPC5	A015-C-104	Human	Colorectum	FAP	7.03e-28	-2.87e-01	-0.1899
51433	ANAPC5	A001-C-014	Human	Colorectum	FAP	9.57e-14	-1.82e-01	0.0135
51433	ANAPC5	A002-C-016	Human	Colorectum	FAP	7.66e-23	-2.67e-01	0.0521
51433	ANAPC5	A015-C-002	Human	Colorectum	FAP	1.71e-09	-2.31e-01	-0.0763
51433	ANAPC5	A001-C-203	Human	Colorectum	FAP	8.09e-10	-1.29e-01	-0.0481

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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
Prostate		BPH: Benign Prostatic Hyperplasia
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:00104983	Colorectum	MSI-H	proteasomal protein catabolic process	71/1319	490/18723	4.67e-09	6.03e-07	71
GO:00431613	Colorectum	MSI-H	proteasome-mediated ubiquitin-dependent protein catabolic process	53/1319	412/18723	1.51e-05	6.62e-04	53
GO:00431614	Colorectum	FAP	proteasome-mediated ubiquitin-dependent protein catabolic process	98/2622	412/18723	5.41e-08	4.20e-06	98
GO:00104984	Colorectum	FAP	proteasomal protein catabolic process	110/2622	490/18723	2.12e-07	1.26e-05	110
GO:00002093	Colorectum	FAP	protein polyubiquitination	59/2622	236/18723	4.53e-06	1.52e-04	59
GO:00330442	Colorectum	FAP	regulation of chromosome organization	46/2622	187/18723	7.41e-05	1.36e-03	46
GO:00457872	Colorectum	FAP	positive regulation of cell cycle	66/2622	313/18723	3.66e-04	4.63e-03	66
GO:00073462	Colorectum	FAP	regulation of mitotic cell cycle	85/2622	457/18723	3.41e-03	2.48e-02	85
GO:00900681	Colorectum	FAP	positive regulation of cell cycle process	48/2622	236/18723	4.53e-03	3.08e-02	48

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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
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
hsa0412026	Esophagus	HGIN	Ubiquitin mediated proteolysis	49/1383	142/8465	7.78e-08	1.33e-06	1.06e-06	49
hsa0516639	Esophagus	HGIN	Human T-cell leukemia virus 1 infection	51/1383	222/8465	5.84e-03	4.05e-02	3.22e-02	51
hsa041109	Esophagus	HGIN	Cell cycle	38/1383	157/8465	6.70e-03	4.37e-02	3.47e-02	38
hsa0465726	Esophagus	HGIN	IL-17 signaling pathway	25/1383	94/8465	7.52e-03	4.63e-02	3.68e-02	25
hsa04120111	Esophagus	HGIN	Ubiquitin mediated proteolysis	49/1383	142/8465	7.78e-08	1.33e-06	1.06e-06	49
hsa05166114	Esophagus	HGIN	Human T-cell leukemia virus 1 infection	51/1383	222/8465	5.84e-03	4.05e-02	3.22e-02	51
hsa0411016	Esophagus	HGIN	Cell cycle	38/1383	157/8465	6.70e-03	4.37e-02	3.47e-02	38
hsa04657113	Esophagus	HGIN	IL-17 signaling pathway	25/1383	94/8465	7.52e-03	4.63e-02	3.68e-02	25
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

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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

ANAPC5

SNV

Missense_Mutation

novel

c.351T>G

p.Asp117Glu

p.D117E

Q9UJX4

protein_coding

tolerated(0.26)

benign(0.01)

TCGA-A2-A0CL-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

ANAPC5

SNV

Missense_Mutation

rs778284423

c.1984N>T

p.Arg662Cys

p.R662C

Q9UJX4

protein_coding

tolerated(0.19)

benign(0.003)

TCGA-AR-A1AI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

ANAPC5

SNV

Missense_Mutation

c.677N>T

p.Asp226Val

p.D226V

Q9UJX4

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-BH-A0DL-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

ANAPC5

SNV

Missense_Mutation

c.271A>G

p.Asn91Asp

p.N91D

Q9UJX4

protein_coding

tolerated(0.57)

benign(0.026)

TCGA-D8-A1XQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ANAPC5

SNV

Missense_Mutation

rs747383939

c.2164N>G

p.His722Asp

p.H722D

Q9UJX4

protein_coding

deleterious(0.04)

benign(0.015)

TCGA-UL-AAZ6-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

herceptin

ANAPC5

SNV

Missense_Mutation

rs552135290

c.1534C>A

p.Gln512Lys

p.Q512K

Q9UJX4

protein_coding

tolerated(0.32)

benign(0.024)

TCGA-DG-A2KJ-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

ANAPC5

SNV

Missense_Mutation

novel

c.1765N>C

p.Glu589Gln

p.E589Q

Q9UJX4

protein_coding

tolerated(0.24)

benign(0.056)

TCGA-Q1-A73O-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ANAPC5

SNV

Missense_Mutation

c.1553N>C

p.Arg518Thr

p.R518T

Q9UJX4

protein_coding

deleterious(0.01)

benign(0.162)

TCGA-Q1-A73O-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ANAPC5

SNV

Missense_Mutation

novel

c.595N>C

p.Glu199Gln

p.E199Q

Q9UJX4

protein_coding

tolerated(0.06)

benign(0.196)

TCGA-VS-A958-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ANAPC5

SNV

Missense_Mutation

c.770G>A

p.Ser257Asn

p.S257N

Q9UJX4

protein_coding

tolerated(0.12)

benign(0.103)

TCGA-AA-3672-01

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

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