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: ANAPC4

Gene summary for ANAPC4

Gene summary.

Gene information	Species	Human
	Gene symbol	ANAPC4
	Gene ID	29945
	Gene name	anaphase promoting complex subunit 4
	Gene Alias	APC4
	Cytomap	4p15.2
	Gene Type	protein-coding
	GO ID	GO:0000070
	UniProtAcc	B3KN47

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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
29945	ANAPC4	AEH-subject3	Human	Endometrium	AEH	1.76e-06	4.01e-01	-0.2576
29945	ANAPC4	AEH-subject4	Human	Endometrium	AEH	1.91e-08	4.85e-01	-0.2657
29945	ANAPC4	EEC-subject3	Human	Endometrium	EEC	1.10e-08	-1.89e-01	-0.2525
29945	ANAPC4	GSM5276934	Human	Endometrium	EEC	2.15e-18	-4.12e-01	-0.0913
29945	ANAPC4	GSM5276935	Human	Endometrium	EEC	3.74e-03	-1.92e-01	-0.123
29945	ANAPC4	GSM5276937	Human	Endometrium	EEC	2.95e-05	-2.72e-01	-0.0897
29945	ANAPC4	GSM6177620_NYU_UCEC1_lib1_lib1	Human	Endometrium	EEC	6.25e-11	-2.91e-01	-0.1869
29945	ANAPC4	GSM6177620_NYU_UCEC1_lib2_lib2	Human	Endometrium	EEC	1.08e-07	-3.41e-01	-0.1875
29945	ANAPC4	GSM6177620_NYU_UCEC1_lib3_lib3	Human	Endometrium	EEC	1.66e-16	-2.22e-01	-0.1883
29945	ANAPC4	GSM6177621_NYU_UCEC2_lib1_lib1	Human	Endometrium	EEC	8.04e-09	9.86e-02	-0.1934
29945	ANAPC4	GSM6177622_NYU_UCEC3_lib1_lib1	Human	Endometrium	EEC	5.33e-16	-3.39e-01	-0.1917
29945	ANAPC4	GSM6177622_NYU_UCEC3_lib2_lib2	Human	Endometrium	EEC	2.16e-17	-3.00e-01	-0.1916
29945	ANAPC4	LZE7T	Human	Esophagus	ESCC	1.87e-03	2.14e-01	0.0667
29945	ANAPC4	LZE24T	Human	Esophagus	ESCC	1.38e-07	1.29e-01	0.0596
29945	ANAPC4	P1T-E	Human	Esophagus	ESCC	4.20e-03	2.95e-01	0.0875
29945	ANAPC4	P2T-E	Human	Esophagus	ESCC	1.06e-22	3.02e-01	0.1177
29945	ANAPC4	P4T-E	Human	Esophagus	ESCC	1.12e-17	2.22e-01	0.1323
29945	ANAPC4	P5T-E	Human	Esophagus	ESCC	6.95e-03	7.63e-02	0.1327
29945	ANAPC4	P8T-E	Human	Esophagus	ESCC	4.53e-13	2.07e-01	0.0889
29945	ANAPC4	P9T-E	Human	Esophagus	ESCC	5.59e-06	5.18e-02	0.1131

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias

∗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: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
GO:00513062	Esophagus	ESCC	mitotic sister chromatid separation	52/8552	67/18723	9.14e-08	1.52e-06	52
GO:00330452	Esophagus	ESCC	regulation of sister chromatid segregation	55/8552	72/18723	1.03e-07	1.69e-06	55

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0412016	Endometrium	AEH	Ubiquitin mediated proteolysis	41/1197	142/8465	3.42e-06	4.27e-05	3.13e-05	41
hsa0516626	Endometrium	AEH	Human T-cell leukemia virus 1 infection	50/1197	222/8465	4.30e-04	3.11e-03	2.27e-03	50
hsa0412017	Endometrium	AEH	Ubiquitin mediated proteolysis	41/1197	142/8465	3.42e-06	4.27e-05	3.13e-05	41
hsa05166111	Endometrium	AEH	Human T-cell leukemia virus 1 infection	50/1197	222/8465	4.30e-04	3.11e-03	2.27e-03	50
hsa0516627	Endometrium	EEC	Human T-cell leukemia virus 1 infection	52/1237	222/8465	2.73e-04	2.36e-03	1.76e-03	52
hsa0516636	Endometrium	EEC	Human T-cell leukemia virus 1 infection	52/1237	222/8465	2.73e-04	2.36e-03	1.76e-03	52
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

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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

ANAPC4

SNV

Missense_Mutation

c.1396N>G

p.Arg466Gly

p.R466G

Q9UJX5

protein_coding

deleterious(0.03)

benign(0.182)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

ANAPC4

SNV

Missense_Mutation

novel

c.86N>G

p.Ser29Trp

p.S29W

Q9UJX5

protein_coding

deleterious(0)

probably_damaging(0.986)

TCGA-A2-A3XZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

ANAPC4

SNV

Missense_Mutation

novel

c.500N>C

p.Leu167Pro

p.L167P

Q9UJX5

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-HN-A2NL-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

ANAPC4

insertion

Frame_Shift_Ins

novel

c.2406_2407insAACCAACTCAGGAATGAAAAGGGGAT

p.Leu803AsnfsTer14

p.L803Nfs*14

Q9UJX5

protein_coding

TCGA-AR-A0U0-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ANAPC4

deletion

Frame_Shift_Del

c.438delN

p.Asn148ThrfsTer67

p.N148Tfs*67

Q9UJX5

protein_coding

TCGA-D8-A1XQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ANAPC4

deletion

Frame_Shift_Del

novel

c.1044delN

p.Ile349Ter

p.I349*

Q9UJX5

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

ANAPC4

SNV

Missense_Mutation

c.616N>T

p.Leu206Phe

p.L206F

Q9UJX5

protein_coding

tolerated(0.32)

benign(0.03)

TCGA-C5-A901-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

ANAPC4

SNV

Missense_Mutation

rs573056698

c.1703G>A

p.Arg568His

p.R568H

Q9UJX5

protein_coding

tolerated(0.17)

benign(0)

TCGA-MA-AA42-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

ANAPC4

SNV

Missense_Mutation

c.463N>C

p.Ile155Leu

p.I155L

Q9UJX5

protein_coding

deleterious(0.03)

probably_damaging(0.952)

TCGA-AA-A00N-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

ANAPC4

SNV

Missense_Mutation

novel

c.133N>G

p.Leu45Val

p.L45V

Q9UJX5

protein_coding

tolerated(0.28)

probably_damaging(0.997)

TCGA-CA-6717-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

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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