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: ANAPC7

Gene summary for ANAPC7

Gene summary.

Gene information	Species	Human
	Gene symbol	ANAPC7
	Gene ID	51434
	Gene name	anaphase promoting complex subunit 7
	Gene Alias	APC7
	Cytomap	12q24.11
	Gene Type	protein-coding
	GO ID	GO:0000070
	UniProtAcc	Q9UJX3

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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
51434	ANAPC7	LZE2T	Human	Esophagus	ESCC	2.53e-05	5.06e-01	0.082
51434	ANAPC7	LZE4T	Human	Esophagus	ESCC	6.12e-13	1.96e-01	0.0811
51434	ANAPC7	LZE7T	Human	Esophagus	ESCC	2.25e-10	4.94e-01	0.0667
51434	ANAPC7	LZE8T	Human	Esophagus	ESCC	1.15e-06	2.71e-01	0.067
51434	ANAPC7	LZE20T	Human	Esophagus	ESCC	7.25e-09	2.05e-01	0.0662
51434	ANAPC7	LZE21D1	Human	Esophagus	HGIN	7.59e-04	2.75e-01	0.0632
51434	ANAPC7	LZE22T	Human	Esophagus	ESCC	9.57e-05	4.83e-01	0.068
51434	ANAPC7	LZE24T	Human	Esophagus	ESCC	7.29e-11	2.74e-01	0.0596
51434	ANAPC7	LZE21T	Human	Esophagus	ESCC	1.84e-05	4.92e-01	0.0655
51434	ANAPC7	LZE6T	Human	Esophagus	ESCC	4.44e-02	1.16e-01	0.0845
51434	ANAPC7	P1T-E	Human	Esophagus	ESCC	4.54e-07	3.09e-01	0.0875
51434	ANAPC7	P2T-E	Human	Esophagus	ESCC	4.10e-40	8.03e-01	0.1177
51434	ANAPC7	P4T-E	Human	Esophagus	ESCC	8.60e-25	4.84e-01	0.1323
51434	ANAPC7	P5T-E	Human	Esophagus	ESCC	6.53e-24	2.93e-01	0.1327
51434	ANAPC7	P8T-E	Human	Esophagus	ESCC	2.34e-18	3.34e-01	0.0889
51434	ANAPC7	P9T-E	Human	Esophagus	ESCC	1.34e-12	1.97e-01	0.1131
51434	ANAPC7	P10T-E	Human	Esophagus	ESCC	9.60e-29	4.34e-01	0.116
51434	ANAPC7	P11T-E	Human	Esophagus	ESCC	3.50e-17	6.07e-01	0.1426
51434	ANAPC7	P12T-E	Human	Esophagus	ESCC	4.34e-29	4.51e-01	0.1122
51434	ANAPC7	P15T-E	Human	Esophagus	ESCC	4.68e-37	6.06e-01	0.1149

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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
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:001049826	Esophagus	HGIN	proteasomal protein catabolic process	139/2587	490/18723	1.20e-17	3.41e-15	139
GO:004316126	Esophagus	HGIN	proteasome-mediated ubiquitin-dependent protein catabolic process	114/2587	412/18723	7.00e-14	1.20e-11	114
GO:00330449	Esophagus	HGIN	regulation of chromosome organization	51/2587	187/18723	8.91e-07	3.61e-05	51
GO:000734610	Esophagus	HGIN	regulation of mitotic cell cycle	98/2587	457/18723	4.39e-06	1.42e-04	98
GO:000020916	Esophagus	HGIN	protein polyubiquitination	58/2587	236/18723	6.29e-06	1.97e-04	58
GO:00447729	Esophagus	HGIN	mitotic cell cycle phase transition	89/2587	424/18723	2.80e-05	7.21e-04	89
GO:19019906	Esophagus	HGIN	regulation of mitotic cell cycle phase transition	65/2587	299/18723	1.12e-04	2.36e-03	65
GO:01400146	Esophagus	HGIN	mitotic nuclear division	61/2587	287/18723	3.38e-04	5.55e-03	61
GO:00070593	Esophagus	HGIN	chromosome segregation	71/2587	346/18723	3.47e-04	5.62e-03	71
GO:00709794	Esophagus	HGIN	protein K11-linked ubiquitination	11/2587	29/18723	1.08e-03	1.32e-02	11
GO:004593110	Esophagus	HGIN	positive regulation of mitotic cell cycle	28/2587	121/18723	3.72e-03	3.39e-02	28
GO:00000703	Esophagus	HGIN	mitotic sister chromatid segregation	36/2587	168/18723	4.42e-03	3.87e-02	36
GO:19019876	Esophagus	HGIN	regulation of cell cycle phase transition	72/2587	390/18723	5.78e-03	4.70e-02	72
GO:0010498111	Esophagus	ESCC	proteasomal protein catabolic process	369/8552	490/18723	1.13e-41	1.80e-38	369
GO:0043161111	Esophagus	ESCC	proteasome-mediated ubiquitin-dependent protein catabolic process	312/8552	412/18723	3.53e-36	4.48e-33	312
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

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
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
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

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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

ANAPC7

SNV

Missense_Mutation

c.257C>T

p.Ser86Phe

p.S86F

Q9UJX3

protein_coding

deleterious(0)

possibly_damaging(0.834)

TCGA-AO-A1KS-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

ANAPC7

SNV

Missense_Mutation

c.430N>A

p.Glu144Lys

p.E144K

Q9UJX3

protein_coding

tolerated(0.88)

benign(0.003)

TCGA-B6-A0RV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

ANAPC7

SNV

Missense_Mutation

rs763204221

c.1243N>A

p.Glu415Lys

p.E415K

Q9UJX3

protein_coding

deleterious(0.04)

benign(0.058)

TCGA-C8-A1HM-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

ANAPC7

SNV

Missense_Mutation

c.1348G>A

p.Val450Ile

p.V450I

Q9UJX3

protein_coding

deleterious(0)

benign(0.083)

TCGA-E9-A1RF-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

tamoxiphen

ANAPC7

SNV

Missense_Mutation

novel

c.326N>A

p.Ala109Glu

p.A109E

Q9UJX3

protein_coding

deleterious(0.03)

benign(0.052)

TCGA-S3-AA15-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

ANAPC7

insertion

Frame_Shift_Ins

novel

c.587_588insT

p.Arg197GlufsTer8

p.R197Efs*8

Q9UJX3

protein_coding

TCGA-BH-A0HW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

ANAPC7

insertion

Frame_Shift_Ins

novel

c.585_586insAGAGCCACAAAGTTAATTCAGTGTT

p.Leu196ArgfsTer17

p.L196Rfs*17

Q9UJX3

protein_coding

TCGA-BH-A0HW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

ANAPC7

SNV

Missense_Mutation

c.1042C>G

p.His348Asp

p.H348D

Q9UJX3

protein_coding

tolerated(0.18)

possibly_damaging(0.564)

TCGA-JW-A5VI-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

topotecan

ANAPC7

SNV

Missense_Mutation

novel

c.1562C>T

p.Ala521Val

p.A521V

Q9UJX3

protein_coding

tolerated(0.11)

benign(0.003)

TCGA-VS-A9UJ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

ANAPC7

SNV

Missense_Mutation

rs372040468

c.1297N>A

p.Val433Ile

p.V433I

Q9UJX3

protein_coding

tolerated(0.13)

benign(0.001)

TCGA-AA-3966-01

Colorectum

colon adenocarcinoma

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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