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: ANAPC1

Gene summary for ANAPC1

Gene summary.

Gene information	Species	Human
	Gene symbol	ANAPC1
	Gene ID	64682
	Gene name	anaphase promoting complex subunit 1
	Gene Alias	APC1
	Cytomap	2q13
	Gene Type	protein-coding
	GO ID	GO:0000070
	UniProtAcc	Q9H1A4

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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
64682	ANAPC1	LZE4T	Human	Esophagus	ESCC	2.10e-02	8.22e-02	0.0811
64682	ANAPC1	LZE7T	Human	Esophagus	ESCC	3.13e-10	2.85e-01	0.0667
64682	ANAPC1	LZE8T	Human	Esophagus	ESCC	1.30e-05	1.18e-01	0.067
64682	ANAPC1	LZE20T	Human	Esophagus	ESCC	1.27e-02	1.37e-01	0.0662
64682	ANAPC1	LZE24T	Human	Esophagus	ESCC	8.74e-13	2.99e-01	0.0596
64682	ANAPC1	P1T-E	Human	Esophagus	ESCC	4.00e-06	2.46e-01	0.0875
64682	ANAPC1	P2T-E	Human	Esophagus	ESCC	2.86e-20	2.52e-01	0.1177
64682	ANAPC1	P4T-E	Human	Esophagus	ESCC	6.09e-22	5.61e-01	0.1323
64682	ANAPC1	P5T-E	Human	Esophagus	ESCC	6.71e-12	2.39e-01	0.1327
64682	ANAPC1	P8T-E	Human	Esophagus	ESCC	1.85e-18	2.72e-01	0.0889
64682	ANAPC1	P9T-E	Human	Esophagus	ESCC	4.03e-13	3.58e-01	0.1131
64682	ANAPC1	P10T-E	Human	Esophagus	ESCC	1.15e-45	6.87e-01	0.116
64682	ANAPC1	P11T-E	Human	Esophagus	ESCC	4.42e-03	2.02e-01	0.1426
64682	ANAPC1	P12T-E	Human	Esophagus	ESCC	9.67e-18	3.44e-01	0.1122
64682	ANAPC1	P15T-E	Human	Esophagus	ESCC	3.86e-23	4.04e-01	0.1149
64682	ANAPC1	P16T-E	Human	Esophagus	ESCC	4.67e-20	2.61e-01	0.1153
64682	ANAPC1	P17T-E	Human	Esophagus	ESCC	3.93e-04	2.65e-01	0.1278
64682	ANAPC1	P19T-E	Human	Esophagus	ESCC	2.11e-07	3.56e-01	0.1662
64682	ANAPC1	P20T-E	Human	Esophagus	ESCC	7.41e-13	2.92e-01	0.1124
64682	ANAPC1	P21T-E	Human	Esophagus	ESCC	1.61e-29	5.48e-01	0.1617

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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
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma

∗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
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
hsa0516630	Oral cavity	OSCC	Human T-cell leukemia virus 1 infection	150/3704	222/8465	3.68e-13	7.26e-12	3.70e-12	150
hsa05166113	Oral cavity	OSCC	Human T-cell leukemia virus 1 infection	150/3704	222/8465	3.68e-13	7.26e-12	3.70e-12	150

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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

ANAPC1

SNV

Missense_Mutation

c.2765N>T

p.Ser922Phe

p.S922F

Q9H1A4

protein_coding

tolerated(0.07)

benign(0.347)

TCGA-A2-A0YK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

ANAPC1

SNV

Missense_Mutation

c.1549N>A

p.Pro517Thr

p.P517T

Q9H1A4

protein_coding

tolerated(0.06)

benign(0.003)

TCGA-A8-A06X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ANAPC1

SNV

Missense_Mutation

c.655N>A

p.Glu219Lys

p.E219K

Q9H1A4

protein_coding

deleterious(0.01)

probably_damaging(0.988)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ANAPC1

SNV

Missense_Mutation

c.415N>C

p.Glu139Gln

p.E139Q

Q9H1A4

protein_coding

tolerated(0.29)

benign(0.075)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ANAPC1

SNV

Missense_Mutation

novel

c.5782N>G

p.Leu1928Val

p.L1928V

Q9H1A4

protein_coding

tolerated(0.12)

possibly_damaging(0.899)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ANAPC1

SNV

Missense_Mutation

c.5683N>T

p.Pro1895Ser

p.P1895S

Q9H1A4

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ANAPC1

SNV

Missense_Mutation

novel

c.3620N>A

p.Gly1207Glu

p.G1207E

Q9H1A4

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-BH-A0AZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

ANAPC1

SNV

Missense_Mutation

c.2563N>A

p.Glu855Lys

p.E855K

Q9H1A4

protein_coding

tolerated(0.76)

benign(0.04)

TCGA-BH-A0H7-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

doxorubicin

ANAPC1

SNV

Missense_Mutation

novel

c.4217T>C

p.Leu1406Pro

p.L1406P

Q9H1A4

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-BH-A0HA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ANAPC1

SNV

Missense_Mutation

novel

c.2050N>C

p.Glu684Gln

p.E684Q

Q9H1A4

protein_coding

tolerated(0.07)

benign(0.149)

TCGA-C8-A8HQ-01

Breast

breast invasive carcinoma

Female

<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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