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	P1_cSCC	Human	Skin	cSCC	1.02e-14	6.96e-01	0.0292
1012	CDH13	P2_cSCC	Human	Skin	cSCC	4.06e-16	5.95e-01	-0.024
1012	CDH13	P4_cSCC	Human	Skin	cSCC	1.38e-17	4.58e-01	-0.00290000000000005
1012	CDH13	P10_cSCC	Human	Skin	cSCC	3.46e-34	9.72e-01	0.1017
1012	CDH13	cSCC_p6	Human	Skin	cSCC	2.29e-02	1.21e-01	-0.1989
1012	CDH13	cSCC_p8	Human	Skin	cSCC	1.60e-07	1.94e-01	-0.1971
1012	CDH13	cSCC_p9	Human	Skin	cSCC	3.88e-02	1.76e-01	-0.1991
1012	CDH13	ATC09	Human	Thyroid	ATC	5.47e-05	2.40e-01	0.2871
1012	CDH13	ATC11	Human	Thyroid	ATC	2.02e-16	2.14e+00	0.3386
1012	CDH13	ATC13	Human	Thyroid	ATC	6.38e-17	4.03e-01	0.34
1012	CDH13	ATC1	Human	Thyroid	ATC	8.73e-06	2.79e-01	0.2878
1012	CDH13	ATC2	Human	Thyroid	ATC	1.85e-28	1.85e+00	0.34
1012	CDH13	ATC3	Human	Thyroid	ATC	4.14e-36	2.25e+00	0.338
1012	CDH13	ATC5	Human	Thyroid	ATC	4.38e-08	4.36e-01	0.34

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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:0038127	Colorectum	AD	ERBB signaling pathway	55/3918	121/18723	1.19e-09	8.85e-08	55
GO:0007173	Colorectum	AD	epidermal growth factor receptor signaling pathway	50/3918	108/18723	3.08e-09	2.07e-07	50
GO:0010811	Colorectum	AD	positive regulation of cell-substrate adhesion	53/3918	123/18723	2.30e-08	1.27e-06	53
GO:0010810	Colorectum	AD	regulation of cell-substrate adhesion	81/3918	221/18723	4.80e-08	2.55e-06	81
GO:0031589	Colorectum	AD	cell-substrate adhesion	116/3918	363/18723	4.68e-07	1.76e-05	116
GO:0001952	Colorectum	AD	regulation of cell-matrix adhesion	50/3918	128/18723	2.05e-06	6.05e-05	50
GO:1901184	Colorectum	AD	regulation of ERBB signaling pathway	34/3918	79/18723	7.46e-06	1.82e-04	34
GO:0007265	Colorectum	AD	Ras protein signal transduction	104/3918	337/18723	1.01e-05	2.35e-04	104
GO:0001954	Colorectum	AD	positive regulation of cell-matrix adhesion	27/3918	58/18723	1.12e-05	2.55e-04	27
GO:0001667	Colorectum	AD	ameboidal-type cell migration	137/3918	475/18723	2.17e-05	4.33e-04	137
GO:0042058	Colorectum	AD	regulation of epidermal growth factor receptor signaling pathway	31/3918	73/18723	2.56e-05	4.89e-04	31
GO:0007160	Colorectum	AD	cell-matrix adhesion	75/3918	233/18723	3.56e-05	6.45e-04	75
GO:0097581	Colorectum	AD	lamellipodium organization	35/3918	90/18723	7.39e-05	1.18e-03	35
GO:0016601	Colorectum	AD	Rac protein signal transduction	20/3918	42/18723	1.02e-04	1.53e-03	20
GO:0090132	Colorectum	AD	epithelium migration	105/3918	360/18723	1.18e-04	1.73e-03	105
GO:0010631	Colorectum	AD	epithelial cell migration	104/3918	357/18723	1.33e-04	1.90e-03	104
GO:0030100	Colorectum	AD	regulation of endocytosis	67/3918	211/18723	1.42e-04	2.01e-03	67
GO:0090130	Colorectum	AD	tissue migration	105/3918	365/18723	2.10e-04	2.77e-03	105
GO:0045785	Colorectum	AD	positive regulation of cell adhesion	122/3918	437/18723	2.65e-04	3.28e-03	122
GO:0050673	Colorectum	AD	epithelial cell proliferation	119/3918	437/18723	8.75e-04	8.51e-03	119

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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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