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: ANAPC11

Gene summary for ANAPC11

Gene summary.

Gene information	Species	Human
	Gene symbol	ANAPC11
	Gene ID	51529
	Gene name	anaphase promoting complex subunit 11
	Gene Alias	APC11
	Cytomap	17q25.3
	Gene Type	protein-coding
	GO ID	GO:0000070
	UniProtAcc	A0A024R8S1

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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
51529	ANAPC11	GSM4909308	Human	Breast	IDC	6.56e-32	6.14e-01	0.158
51529	ANAPC11	GSM4909309	Human	Breast	IDC	2.67e-08	2.19e-01	0.0483
51529	ANAPC11	GSM4909311	Human	Breast	IDC	1.80e-45	-1.15e-01	0.1534
51529	ANAPC11	GSM4909312	Human	Breast	IDC	1.30e-15	5.70e-02	0.1552
51529	ANAPC11	GSM4909313	Human	Breast	IDC	3.82e-07	3.15e-02	0.0391
51529	ANAPC11	GSM4909315	Human	Breast	IDC	2.76e-03	2.13e-01	0.21
51529	ANAPC11	GSM4909316	Human	Breast	IDC	2.54e-10	3.68e-01	0.21
51529	ANAPC11	GSM4909318	Human	Breast	IDC	4.05e-15	5.49e-01	0.2031
51529	ANAPC11	GSM4909319	Human	Breast	IDC	1.91e-83	4.44e-01	0.1563
51529	ANAPC11	GSM4909320	Human	Breast	IDC	1.31e-61	9.85e-01	0.1575
51529	ANAPC11	GSM4909321	Human	Breast	IDC	5.60e-57	6.98e-01	0.1559
51529	ANAPC11	brca1	Human	Breast	Precancer	4.71e-04	3.48e-01	-0.0338
51529	ANAPC11	brca2	Human	Breast	Precancer	3.32e-04	2.79e-01	-0.024
51529	ANAPC11	M2	Human	Breast	IDC	2.31e-10	3.67e-01	0.21
51529	ANAPC11	NCCBC14	Human	Breast	DCIS	1.72e-18	-1.84e-02	0.2021
51529	ANAPC11	NCCBC2	Human	Breast	DCIS	1.70e-07	-4.03e-01	0.1554
51529	ANAPC11	NCCBC3	Human	Breast	DCIS	2.88e-05	-5.30e-02	0.1198
51529	ANAPC11	NCCBC5	Human	Breast	DCIS	7.02e-27	1.16e-01	0.2046
51529	ANAPC11	NCCBC6	Human	Breast	DCIS	1.84e-09	2.35e-01	0.2095
51529	ANAPC11	P1	Human	Breast	IDC	1.93e-33	-1.63e-01	0.1527

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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:00104989	Breast	Precancer	proteasomal protein catabolic process	58/1080	490/18723	1.54e-07	8.05e-06	58
GO:00431619	Breast	Precancer	proteasome-mediated ubiquitin-dependent protein catabolic process	42/1080	412/18723	2.49e-04	3.72e-03	42
GO:001049814	Breast	IDC	proteasomal protein catabolic process	75/1434	490/18723	5.59e-09	4.41e-07	75
GO:004316114	Breast	IDC	proteasome-mediated ubiquitin-dependent protein catabolic process	57/1434	412/18723	9.55e-06	2.68e-04	57
GO:00330445	Breast	IDC	regulation of chromosome organization	26/1434	187/18723	2.22e-03	2.06e-02	26
GO:00073465	Breast	IDC	regulation of mitotic cell cycle	51/1434	457/18723	4.30e-03	3.35e-02	51
GO:00459315	Breast	IDC	positive regulation of mitotic cell cycle	18/1434	121/18723	4.90e-03	3.73e-02	18
GO:001049824	Breast	DCIS	proteasomal protein catabolic process	75/1390	490/18723	1.44e-09	1.40e-07	75
GO:004316124	Breast	DCIS	proteasome-mediated ubiquitin-dependent protein catabolic process	57/1390	412/18723	3.76e-06	1.16e-04	57
GO:000734612	Breast	DCIS	regulation of mitotic cell cycle	52/1390	457/18723	1.38e-03	1.43e-02	52
GO:003304412	Breast	DCIS	regulation of chromosome organization	26/1390	187/18723	1.44e-03	1.47e-02	26
GO:004593112	Breast	DCIS	positive regulation of mitotic cell cycle	19/1390	121/18723	1.47e-03	1.49e-02	19
GO:00447724	Breast	DCIS	mitotic cell cycle phase transition	46/1390	424/18723	6.16e-03	4.39e-02	46
GO:001049810	Cervix	CC	proteasomal protein catabolic process	111/2311	490/18723	8.98e-11	1.58e-08	111
GO:004316110	Cervix	CC	proteasome-mediated ubiquitin-dependent protein catabolic process	91/2311	412/18723	1.65e-08	1.25e-06	91
GO:00002097	Cervix	CC	protein polyubiquitination	58/2311	236/18723	1.57e-07	7.41e-06	58
GO:00447725	Cervix	CC	mitotic cell cycle phase transition	89/2311	424/18723	2.70e-07	1.12e-05	89
GO:00457876	Cervix	CC	positive regulation of cell cycle	66/2311	313/18723	7.78e-06	1.81e-04	66
GO:00073466	Cervix	CC	regulation of mitotic cell cycle	88/2311	457/18723	1.26e-05	2.60e-04	88
GO:19019903	Cervix	CC	regulation of mitotic cell cycle phase transition	63/2311	299/18723	1.27e-05	2.60e-04	63

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0516618	Breast	Precancer	Human T-cell leukemia virus 1 infection	33/684	222/8465	4.29e-04	3.31e-03	2.53e-03	33
hsa0516619	Breast	Precancer	Human T-cell leukemia virus 1 infection	33/684	222/8465	4.29e-04	3.31e-03	2.53e-03	33
hsa0516642	Breast	DCIS	Human T-cell leukemia virus 1 infection	41/846	222/8465	7.03e-05	6.88e-04	5.07e-04	41
hsa0516652	Breast	DCIS	Human T-cell leukemia virus 1 infection	41/846	222/8465	7.03e-05	6.88e-04	5.07e-04	41
hsa05166	Colorectum	AD	Human T-cell leukemia virus 1 infection	72/2092	222/8465	5.24e-03	2.44e-02	1.55e-02	72
hsa051661	Colorectum	AD	Human T-cell leukemia virus 1 infection	72/2092	222/8465	5.24e-03	2.44e-02	1.55e-02	72
hsa051662	Colorectum	MSS	Human T-cell leukemia virus 1 infection	68/1875	222/8465	1.84e-03	9.61e-03	5.89e-03	68
hsa051663	Colorectum	MSS	Human T-cell leukemia virus 1 infection	68/1875	222/8465	1.84e-03	9.61e-03	5.89e-03	68
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
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
hsa05166211	Esophagus	ESCC	Human T-cell leukemia virus 1 infection	164/4205	222/8465	8.13e-14	2.09e-12	1.07e-12	164
hsa05166310	Esophagus	ESCC	Human T-cell leukemia virus 1 infection	164/4205	222/8465	8.13e-14	2.09e-12	1.07e-12	164
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

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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

ANAPC11

SNV

Missense_Mutation

c.61N>C

p.Glu21Gln

p.E21Q

Q9NYG5

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(0.975)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ANAPC11

SNV

Missense_Mutation

novel

c.259N>C

p.Glu87Gln

p.E87Q

Q9NYG5

protein_coding

tolerated_low_confidence(0.43)

benign(0.125)

TCGA-HM-A4S6-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

ANAPC11

SNV

Missense_Mutation

rs535288823

c.422N>A

p.Arg141Gln

p.R141Q

Q9NYG5

protein_coding

tolerated_low_confidence(0.22)

benign(0.356)

TCGA-AA-3548-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Chemotherapy

folinic

ANAPC11

SNV

Missense_Mutation

rs781372181

c.562G>A

p.Asp188Asn

p.D188N

Q9NYG5

protein_coding

tolerated_low_confidence(0.08)

benign(0.007)

TCGA-CM-4746-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

ANAPC11

SNV

Missense_Mutation

novel

c.6G>T

p.Lys2Asn

p.K2N

Q9NYG5

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(0.913)

TCGA-AP-A1DP-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Chemotherapy

paclitaxel

ANAPC11

SNV

Missense_Mutation

novel

c.497N>T

p.Arg166Leu

p.R166L

Q9NYG5

protein_coding

tolerated_low_confidence(0.57)

benign(0.035)

TCGA-AP-A1DR-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

ANAPC11

SNV

Missense_Mutation

rs201159530

c.320T>C

p.Leu107Pro

p.L107P

Q9NYG5

protein_coding

deleterious_low_confidence(0)

benign(0.003)

TCGA-B5-A3FC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

ANAPC11

deletion

Frame_Shift_Del

novel

c.362delN

p.Phe122LeufsTer64

p.F122Lfs*64

Q9NYG5

protein_coding

TCGA-BK-A13B-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

ANAPC11

SNV

Missense_Mutation

novel

c.542N>T

p.Glu181Val

p.E181V

Q9NYG5

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.999)

TCGA-4R-AA8I-01

Liver

liver hepatocellular carcinoma

Male

>=65

I/II

Unknown

ANAPC11

SNV

Missense_Mutation

c.443N>C

p.Val148Ala

p.V148A

Q9NYG5

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.879)

TCGA-CG-5721-01

Stomach

stomach adenocarcinoma

Male

<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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