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: APCDD1

Gene summary for APCDD1

Gene summary.

Gene information	Species	Human
	Gene symbol	APCDD1
	Gene ID	147495
	Gene name	APC down-regulated 1
	Gene Alias	B7323
	Cytomap	18p11.22
	Gene Type	protein-coding
	GO ID	GO:0001942
	UniProtAcc	Q8J025

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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
147495	APCDD1	P130T-E	Human	Esophagus	ESCC	6.89e-24	6.38e-01	0.1676
147495	APCDD1	HCC1_Meng	Human	Liver	HCC	4.06e-02	-1.72e-01	0.0246
147495	APCDD1	HCC2_Meng	Human	Liver	HCC	2.98e-03	-9.47e-02	0.0107
147495	APCDD1	cirrhotic2	Human	Liver	Cirrhotic	9.11e-06	8.37e-02	0.0201
147495	APCDD1	S014	Human	Liver	HCC	2.97e-24	2.40e+00	0.2254
147495	APCDD1	S015	Human	Liver	HCC	4.19e-22	2.40e+00	0.2375
147495	APCDD1	S016	Human	Liver	HCC	2.86e-30	2.25e+00	0.2243
147495	APCDD1	C04	Human	Oral cavity	OSCC	7.06e-07	6.21e-01	0.2633
147495	APCDD1	C43	Human	Oral cavity	OSCC	1.66e-02	-1.59e-01	0.1704
147495	APCDD1	C51	Human	Oral cavity	OSCC	1.10e-02	4.35e-01	0.2674
147495	APCDD1	C09	Human	Oral cavity	OSCC	1.13e-06	5.19e-01	0.1431
147495	APCDD1	LP16	Human	Oral cavity	LP	1.35e-02	4.22e-01	0.1055
147495	APCDD1	SYSMH1	Human	Oral cavity	OSCC	3.50e-02	-1.60e-01	0.1127
147495	APCDD1	SYSMH2	Human	Oral cavity	OSCC	6.62e-04	3.54e-01	0.2326
147495	APCDD1	SYSMH3	Human	Oral cavity	OSCC	6.34e-27	9.20e-01	0.2442
147495	APCDD1	SYSMH4	Human	Oral cavity	OSCC	1.51e-02	1.12e-01	0.1226
147495	APCDD1	SYSMH5	Human	Oral cavity	OSCC	3.61e-02	2.11e-01	0.0647
147495	APCDD1	P4_S8_cSCC	Human	Skin	cSCC	9.16e-14	4.25e-01	-0.3095
147495	APCDD1	P5_S10_cSCC	Human	Skin	cSCC	4.57e-03	-1.65e-01	-0.299
147495	APCDD1	P1_cSCC	Human	Skin	cSCC	1.61e-15	1.01e+00	0.0292

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:0030111	Colorectum	AD	regulation of Wnt signaling pathway	102/3918	328/18723	8.51e-06	2.03e-04	102
GO:0016055	Colorectum	AD	Wnt signaling pathway	130/3918	444/18723	1.60e-05	3.37e-04	130
GO:0198738	Colorectum	AD	cell-cell signaling by wnt	130/3918	446/18723	2.02e-05	4.10e-04	130
GO:0008544	Colorectum	AD	epidermis development	87/3918	324/18723	5.99e-03	3.76e-02	87
GO:00301112	Colorectum	MSS	regulation of Wnt signaling pathway	98/3467	328/18723	3.37e-07	1.36e-05	98
GO:00160552	Colorectum	MSS	Wnt signaling pathway	124/3467	444/18723	6.06e-07	2.26e-05	124
GO:01987382	Colorectum	MSS	cell-cell signaling by wnt	124/3467	446/18723	7.83e-07	2.77e-05	124
GO:0030178	Colorectum	MSS	negative regulation of Wnt signaling pathway	48/3467	170/18723	1.23e-03	1.18e-02	48
GO:00160553	Colorectum	FAP	Wnt signaling pathway	104/2622	444/18723	4.92e-08	3.92e-06	104
GO:01987383	Colorectum	FAP	cell-cell signaling by wnt	104/2622	446/18723	6.26e-08	4.54e-06	104
GO:00301113	Colorectum	FAP	regulation of Wnt signaling pathway	81/2622	328/18723	1.44e-07	9.03e-06	81
GO:0043588	Colorectum	FAP	skin development	58/2622	263/18723	2.44e-04	3.39e-03	58
GO:00085441	Colorectum	FAP	epidermis development	66/2622	324/18723	9.63e-04	9.51e-03	66
GO:00301781	Colorectum	FAP	negative regulation of Wnt signaling pathway	38/2622	170/18723	2.06e-03	1.70e-02	38
GO:0022404	Colorectum	FAP	molting cycle process	21/2622	84/18723	5.10e-03	3.37e-02	21
GO:0022405	Colorectum	FAP	hair cycle process	21/2622	84/18723	5.10e-03	3.37e-02	21
GO:00160554	Colorectum	CRC	Wnt signaling pathway	88/2078	444/18723	3.91e-08	5.28e-06	88
GO:01987384	Colorectum	CRC	cell-cell signaling by wnt	88/2078	446/18723	4.85e-08	6.04e-06	88
GO:00301114	Colorectum	CRC	regulation of Wnt signaling pathway	68/2078	328/18723	2.41e-07	2.27e-05	68
GO:00085442	Colorectum	CRC	epidermis development	57/2078	324/18723	2.88e-04	4.59e-03	57

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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

APCDD1

SNV

Missense_Mutation

rs746711951

c.638N>A

p.Arg213Gln

p.R213Q

Q8J025

protein_coding

deleterious(0)

probably_damaging(0.993)

TCGA-A2-A0YJ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

APCDD1

SNV

Missense_Mutation

c.1127N>A

p.Ala376Glu

p.A376E

Q8J025

protein_coding

tolerated(1)

benign(0.028)

TCGA-A2-A25D-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

tamoxiphen

APCDD1

SNV

Missense_Mutation

c.265N>C

p.Glu89Gln

p.E89Q

Q8J025

protein_coding

deleterious(0.04)

possibly_damaging(0.747)

TCGA-D8-A1JA-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

APCDD1

SNV

Missense_Mutation

c.165G>T

p.Met55Ile

p.M55I

Q8J025

protein_coding

tolerated(0.14)

possibly_damaging(0.62)

TCGA-D8-A1XQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

APCDD1

insertion

In_Frame_Ins

novel

c.906_907insTCCACATCACACCTGAAATGTTTGCGTAGGTCTGTACTGTCAGGCAAA

p.Val302_Arg303insSerThrSerHisLeuLysCysLeuArgArgSerValLeuSerGlyLys

p.V302_R303insSTSHLKCLRRSVLSGK

Q8J025

protein_coding

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

APCDD1

deletion

Frame_Shift_Del

novel

c.1515delN

p.Pro506LeufsTer62

p.P506Lfs*62

Q8J025

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

APCDD1

SNV

Missense_Mutation

rs758081145

c.1300N>T

p.Arg434Cys

p.R434C

Q8J025

protein_coding

deleterious(0)

probably_damaging(0.944)

TCGA-A6-5665-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

APCDD1

SNV

Missense_Mutation

rs374082304

c.908N>A

p.Arg303His

p.R303H

Q8J025

protein_coding

deleterious(0.01)

possibly_damaging(0.736)

TCGA-AA-3821-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

APCDD1

SNV

Missense_Mutation

rs758870123

c.932N>A

p.Arg311His

p.R311H

Q8J025

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AA-3952-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Unknown

APCDD1

SNV

Missense_Mutation

rs149564774

c.120N>T

p.Glu40Asp

p.E40D

Q8J025

protein_coding

tolerated(0.07)

benign(0.011)

TCGA-AA-3977-01

Colorectum

colon adenocarcinoma

Male

>=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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