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: ANAPC15

Gene summary for ANAPC15

Gene summary.

Gene information	Species	Human
	Gene symbol	ANAPC15
	Gene ID	25906
	Gene name	anaphase promoting complex subunit 15
	Gene Alias	APC15
	Cytomap	11q13.4
	Gene Type	protein-coding
	GO ID	GO:0000070
	UniProtAcc	P60006

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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
25906	ANAPC15	P19T-E	Human	Esophagus	ESCC	1.07e-07	1.11e+00	0.1662
25906	ANAPC15	P20T-E	Human	Esophagus	ESCC	2.00e-57	1.48e+00	0.1124
25906	ANAPC15	P21T-E	Human	Esophagus	ESCC	8.36e-42	1.01e+00	0.1617
25906	ANAPC15	P22T-E	Human	Esophagus	ESCC	7.85e-24	4.83e-01	0.1236
25906	ANAPC15	P23T-E	Human	Esophagus	ESCC	1.47e-64	1.88e+00	0.108
25906	ANAPC15	P24T-E	Human	Esophagus	ESCC	7.96e-09	2.44e-01	0.1287
25906	ANAPC15	P26T-E	Human	Esophagus	ESCC	3.46e-17	5.38e-01	0.1276
25906	ANAPC15	P27T-E	Human	Esophagus	ESCC	1.45e-25	6.48e-01	0.1055
25906	ANAPC15	P28T-E	Human	Esophagus	ESCC	6.32e-57	1.39e+00	0.1149
25906	ANAPC15	P30T-E	Human	Esophagus	ESCC	7.10e-31	1.23e+00	0.137
25906	ANAPC15	P31T-E	Human	Esophagus	ESCC	2.99e-27	6.94e-01	0.1251
25906	ANAPC15	P32T-E	Human	Esophagus	ESCC	2.21e-53	1.35e+00	0.1666
25906	ANAPC15	P36T-E	Human	Esophagus	ESCC	1.67e-12	3.61e-01	0.1187
25906	ANAPC15	P37T-E	Human	Esophagus	ESCC	1.10e-22	5.25e-01	0.1371
25906	ANAPC15	P38T-E	Human	Esophagus	ESCC	7.04e-07	3.21e-01	0.127
25906	ANAPC15	P39T-E	Human	Esophagus	ESCC	1.43e-05	2.35e-01	0.0894
25906	ANAPC15	P40T-E	Human	Esophagus	ESCC	1.63e-12	3.38e-01	0.109
25906	ANAPC15	P42T-E	Human	Esophagus	ESCC	1.29e-14	4.48e-01	0.1175
25906	ANAPC15	P44T-E	Human	Esophagus	ESCC	8.13e-17	6.97e-01	0.1096
25906	ANAPC15	P47T-E	Human	Esophagus	ESCC	8.67e-14	2.89e-01	0.1067

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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:00330449	Esophagus	HGIN	regulation of chromosome organization	51/2587	187/18723	8.91e-07	3.61e-05	51
GO:001063920	Esophagus	HGIN	negative regulation of organelle organization	79/2587	348/18723	4.12e-06	1.37e-04	79
GO:000734610	Esophagus	HGIN	regulation of mitotic cell cycle	98/2587	457/18723	4.39e-06	1.42e-04	98
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:00459305	Esophagus	HGIN	negative regulation of mitotic cell cycle	49/2587	235/18723	1.88e-03	2.01e-02	49
GO:19019915	Esophagus	HGIN	negative regulation of mitotic cell cycle phase transition	39/2587	179/18723	2.31e-03	2.36e-02	39
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: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: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

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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
hsa0412021	Liver	Cirrhotic	Ubiquitin mediated proteolysis	72/2530	142/8465	1.32e-07	1.97e-06	1.21e-06	72
hsa0516614	Liver	Cirrhotic	Human T-cell leukemia virus 1 infection	87/2530	222/8465	1.69e-03	8.01e-03	4.94e-03	87
hsa041104	Liver	Cirrhotic	Cell cycle	61/2530	157/8465	9.53e-03	3.21e-02	1.98e-02	61
hsa0412031	Liver	Cirrhotic	Ubiquitin mediated proteolysis	72/2530	142/8465	1.32e-07	1.97e-06	1.21e-06	72
hsa0516615	Liver	Cirrhotic	Human T-cell leukemia virus 1 infection	87/2530	222/8465	1.69e-03	8.01e-03	4.94e-03	87
hsa0411011	Liver	Cirrhotic	Cell cycle	61/2530	157/8465	9.53e-03	3.21e-02	1.98e-02	61

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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

ANAPC15

insertion

Nonsense_Mutation

novel

c.15_16insTATTAATTGAGGATCTAGCAGATGAT

p.Pro6TyrfsTer2

p.P6Yfs*2

protein_coding

TCGA-AN-A0FX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ANAPC15

SNV

Missense_Mutation

rs767356574

c.133N>A

p.Ala45Thr

p.A45T

protein_coding

tolerated_low_confidence(0.09)

benign(0.339)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ANAPC15

SNV

Missense_Mutation

novel

c.495N>A

p.Phe165Leu

p.F165L

protein_coding

benign(0.005)

TCGA-C5-A7XC-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

ANAPC15

SNV

Missense_Mutation

novel

c.14T>G

p.Phe5Cys

p.F5C

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.993)

TCGA-EK-A2PL-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

ANAPC15

SNV

Missense_Mutation

novel

c.457N>T

p.Pro153Ser

p.P153S

protein_coding

deleterious_low_confidence(0)

benign(0.003)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

ANAPC15

SNV

Missense_Mutation

novel

c.13N>C

p.Phe5Leu

p.F5L

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.953)

TCGA-AP-A059-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

ANAPC15

SNV

Missense_Mutation

novel

c.268G>A

p.Asp90Asn

p.D90N

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(0.99)

TCGA-AP-A0LM-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

ANAPC15

SNV

Missense_Mutation

novel

c.138G>T

p.Glu46Asp

p.E46D

protein_coding

deleterious_low_confidence(0.04)

benign(0.201)

TCGA-B5-A1MR-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Unknown

ANAPC15

SNV

Missense_Mutation

novel

c.40N>A

p.Glu14Lys

p.E14K

protein_coding

deleterious_low_confidence(0.05)

benign(0.133)

TCGA-B5-A3FA-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

ANAPC15

SNV

Missense_Mutation

rs767356574

c.133N>A

p.Ala45Thr

p.A45T

protein_coding

tolerated_low_confidence(0.09)

benign(0.339)

TCGA-B5-A3FC-01

Endometrium

uterine corpus endometrioid 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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