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: CDH13

Gene summary for CDH13

Gene summary.

Gene information	Species	Human
	Gene symbol	CDH13
	Gene ID	1012
	Gene name	cadherin 13
	Gene Alias	CDHH
	Cytomap	16q23.3
	Gene Type	protein-coding
	GO ID	GO:0000278
	UniProtAcc	B7Z9B1

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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
1012	CDH13	HTA11_1938_2000001011	Human	Colorectum	AD	1.52e-04	4.83e-01	-0.0811
1012	CDH13	HTA11_78_2000001011	Human	Colorectum	AD	5.36e-10	5.65e-01	-0.1088
1012	CDH13	HTA11_347_2000001011	Human	Colorectum	AD	5.78e-16	8.56e-01	-0.1954
1012	CDH13	HTA11_3361_2000001011	Human	Colorectum	AD	2.04e-02	3.78e-01	-0.1207
1012	CDH13	HTA11_696_2000001011	Human	Colorectum	AD	9.44e-05	3.62e-01	-0.1464
1012	CDH13	HTA11_866_2000001011	Human	Colorectum	AD	9.35e-05	4.47e-01	-0.1001
1012	CDH13	HTA11_99999970781_79442	Human	Colorectum	MSS	1.17e-09	5.27e-01	0.294
1012	CDH13	HTA11_99999965062_69753	Human	Colorectum	MSI-H	4.32e-09	1.64e+00	0.3487
1012	CDH13	A002-C-203	Human	Colorectum	FAP	8.13e-03	-8.89e-02	0.2786
1012	CDH13	LZE2T	Human	Esophagus	ESCC	3.62e-02	3.09e-01	0.082
1012	CDH13	LZE4T	Human	Esophagus	ESCC	7.36e-21	6.58e-01	0.0811
1012	CDH13	LZE7T	Human	Esophagus	ESCC	1.17e-07	3.85e-01	0.0667
1012	CDH13	LZE22T	Human	Esophagus	ESCC	4.76e-02	2.02e-01	0.068
1012	CDH13	LZE21T	Human	Esophagus	ESCC	1.71e-06	7.78e-01	0.0655
1012	CDH13	P2T-E	Human	Esophagus	ESCC	4.83e-07	2.20e-01	0.1177
1012	CDH13	P4T-E	Human	Esophagus	ESCC	3.11e-03	-4.77e-03	0.1323
1012	CDH13	P5T-E	Human	Esophagus	ESCC	1.36e-12	1.19e-01	0.1327
1012	CDH13	P9T-E	Human	Esophagus	ESCC	3.96e-07	1.40e-01	0.1131
1012	CDH13	P10T-E	Human	Esophagus	ESCC	5.19e-33	8.07e-01	0.116
1012	CDH13	P11T-E	Human	Esophagus	ESCC	9.51e-16	6.51e-01	0.1426

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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
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
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:00166012	Colorectum	FAP	Rac protein signal transduction	14/2622	42/18723	1.20e-03	1.14e-02	14
GO:00506732	Colorectum	FAP	epithelial cell proliferation	84/2622	437/18723	1.39e-03	1.25e-02	84
GO:00071621	Colorectum	FAP	negative regulation of cell adhesion	61/2622	303/18723	1.96e-03	1.65e-02	61
GO:00436162	Colorectum	FAP	keratinocyte proliferation	14/2622	46/18723	3.17e-03	2.37e-02	14
GO:00435423	Colorectum	FAP	endothelial cell migration	55/2622	279/18723	5.00e-03	3.33e-02	55
GO:00486601	Colorectum	FAP	regulation of smooth muscle cell proliferation	38/2622	180/18723	5.73e-03	3.67e-02	38
GO:00506781	Colorectum	FAP	regulation of epithelial cell proliferation	71/2622	381/18723	6.67e-03	4.12e-02	71
GO:00486591	Colorectum	FAP	smooth muscle cell proliferation	38/2622	184/18723	8.29e-03	4.85e-02	38
GO:003158919	Esophagus	ESCC	cell-substrate adhesion	221/8552	363/18723	3.06e-09	6.62e-08	221
GO:001081020	Esophagus	ESCC	regulation of cell-substrate adhesion	144/8552	221/18723	3.55e-09	7.45e-08	144
GO:004578527	Esophagus	ESCC	positive regulation of cell adhesion	255/8552	437/18723	5.07e-08	9.11e-07	255
GO:003010018	Esophagus	ESCC	regulation of endocytosis	135/8552	211/18723	5.75e-08	1.02e-06	135
GO:000726510	Esophagus	ESCC	Ras protein signal transduction	201/8552	337/18723	1.44e-07	2.30e-06	201
GO:001081126	Esophagus	ESCC	positive regulation of cell-substrate adhesion	84/8552	123/18723	3.18e-07	4.50e-06	84
GO:003812718	Esophagus	ESCC	ERBB signaling pathway	82/8552	121/18723	7.23e-07	9.40e-06	82
GO:000195217	Esophagus	ESCC	regulation of cell-matrix adhesion	85/8552	128/18723	1.70e-06	2.02e-05	85
GO:000716018	Esophagus	ESCC	cell-matrix adhesion	141/8552	233/18723	3.33e-06	3.71e-05	141
GO:000717318	Esophagus	ESCC	epidermal growth factor receptor signaling pathway	73/8552	108/18723	3.36e-06	3.73e-05	73
GO:00166019	Esophagus	ESCC	Rac protein signal transduction	33/8552	42/18723	1.35e-05	1.23e-04	33
GO:190118413	Esophagus	ESCC	regulation of ERBB signaling pathway	54/8552	79/18723	3.81e-05	3.08e-04	54

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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

CDH13

SNV

Missense_Mutation

novel

c.1360N>A

p.Pro454Thr

p.P454T

P55290

protein_coding

deleterious(0.02)

benign(0.426)

TCGA-A2-A0EM-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

CDH13

SNV

Missense_Mutation

rs372445890

c.1510N>A

p.Gly504Ser

p.G504S

P55290

protein_coding

tolerated(0.73)

probably_damaging(0.997)

TCGA-A8-A08T-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

CDH13

SNV

Missense_Mutation

novel

c.1414T>C

p.Ser472Pro

p.S472P

P55290

protein_coding

deleterious(0.01)

probably_damaging(0.981)

TCGA-A8-A094-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CDH13

SNV

Missense_Mutation

novel

c.1954N>C

p.Gly652Arg

p.G652R

P55290

protein_coding

tolerated(0.14)

probably_damaging(0.999)

TCGA-D8-A73U-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

CDH13

insertion

Nonsense_Mutation

novel

c.1332_1333insCGGCTCAAAGGAATGTGCTAATGAAAGCTCATGAAATTCTCTATCTAT

p.Arg444_Ala445insArgLeuLysGlyMetCysTerTerLysLeuMetLysPheSerIleTyr

p.R444_A445insRLKGMC**KLMKFSIY

P55290

protein_coding

TCGA-BH-A0EE-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

docetaxel

CDH13

SNV

Missense_Mutation

rs868363122

c.1078T>C

p.Ser360Pro

p.S360P

P55290

protein_coding

tolerated(0.1)

benign(0.003)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CDH13

SNV

Missense_Mutation

novel

c.1910C>A

p.Ala637Asp

p.A637D

P55290

protein_coding

deleterious(0.01)

probably_damaging(0.996)

TCGA-EK-A2PG-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

CDH13

SNV

Missense_Mutation

c.2186G>A

p.Cys729Tyr

p.C729Y

P55290

protein_coding

deleterious(0)

possibly_damaging(0.56)

TCGA-IR-A3LH-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CDH13

SNV

Missense_Mutation

c.240N>C

p.Gln80His

p.Q80H

P55290

protein_coding

deleterious(0.04)

benign(0.444)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

CDH13

SNV

Missense_Mutation

novel

c.1213N>C

p.Asp405His

p.D405H

P55290

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-VS-A959-01

Cervix

cervical & endocervical cancer

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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