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:00106312	Colorectum	MSS	epithelial cell migration	92/3467	357/18723	3.87e-04	4.86e-03	92
GO:00420581	Colorectum	MSS	regulation of epidermal growth factor receptor signaling pathway	26/3467	73/18723	4.05e-04	4.99e-03	26
GO:00901302	Colorectum	MSS	tissue migration	93/3467	365/18723	5.42e-04	6.06e-03	93
GO:00506731	Colorectum	MSS	epithelial cell proliferation	108/3467	437/18723	6.76e-04	7.30e-03	108
GO:00166011	Colorectum	MSS	Rac protein signal transduction	17/3467	42/18723	7.63e-04	8.10e-03	17
GO:00300321	Colorectum	MSS	lamellipodium assembly	24/3467	72/18723	1.91e-03	1.66e-02	24
GO:00435422	Colorectum	MSS	endothelial cell migration	70/3467	279/18723	3.69e-03	2.71e-02	70
GO:0048659	Colorectum	MSS	smooth muscle cell proliferation	49/3467	184/18723	4.08e-03	2.97e-02	49
GO:0048660	Colorectum	MSS	regulation of smooth muscle cell proliferation	48/3467	180/18723	4.32e-03	3.07e-02	48
GO:0048661	Colorectum	MSS	positive regulation of smooth muscle cell proliferation	30/3467	104/18723	6.69e-03	4.38e-02	30
GO:0050678	Colorectum	MSS	regulation of epithelial cell proliferation	90/3467	381/18723	6.92e-03	4.45e-02	90
GO:00108113	Colorectum	MSI-H	positive regulation of cell-substrate adhesion	20/1319	123/18723	3.67e-04	8.46e-03	20
GO:00106313	Colorectum	MSI-H	epithelial cell migration	42/1319	357/18723	7.51e-04	1.42e-02	42
GO:00901323	Colorectum	MSI-H	epithelium migration	42/1319	360/18723	8.89e-04	1.58e-02	42
GO:00901303	Colorectum	MSI-H	tissue migration	42/1319	365/18723	1.17e-03	1.92e-02	42
GO:00457853	Colorectum	MSI-H	positive regulation of cell adhesion	48/1319	437/18723	1.47e-03	2.23e-02	48
GO:00975813	Colorectum	MSI-H	lamellipodium organization	15/1319	90/18723	1.48e-03	2.23e-02	15
GO:00108103	Colorectum	MSI-H	regulation of cell-substrate adhesion	28/1319	221/18723	1.83e-03	2.63e-02	28
GO:00381273	Colorectum	MSI-H	ERBB signaling pathway	18/1319	121/18723	2.01e-03	2.83e-02	18
GO:00071733	Colorectum	MSI-H	epidermal growth factor receptor signaling pathway	16/1319	108/18723	3.63e-03	4.28e-02	16

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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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