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: CELSR1

Gene summary for CELSR1

Gene summary.

Gene information	Species	Human
	Gene symbol	CELSR1
	Gene ID	9620
	Gene name	cadherin EGF LAG seven-pass G-type receptor 1
	Gene Alias	ADGRC1
	Cytomap	22q13.31
	Gene Type	protein-coding
	GO ID	GO:0001736
	UniProtAcc	Q9NYQ6

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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
9620	CELSR1	GSM4909293	Human	Breast	IDC	2.75e-04	1.51e-01	0.1581
9620	CELSR1	GSM4909306	Human	Breast	IDC	6.31e-06	1.88e-01	0.1564
9620	CELSR1	GSM4909307	Human	Breast	IDC	6.87e-07	2.37e-01	0.1569
9620	CELSR1	GSM4909308	Human	Breast	IDC	2.12e-07	2.24e-01	0.158
9620	CELSR1	GSM4909317	Human	Breast	IDC	9.13e-05	1.59e-01	0.1355
9620	CELSR1	M5	Human	Breast	IDC	2.00e-02	3.32e-01	0.1598
9620	CELSR1	NCCBC2	Human	Breast	DCIS	2.73e-03	5.40e-01	0.1554
9620	CELSR1	P3	Human	Breast	IDC	2.53e-06	5.17e-01	0.1542
9620	CELSR1	DCIS2	Human	Breast	DCIS	6.56e-05	1.61e-02	0.0085
9620	CELSR1	CA_HPV_1	Human	Cervix	CC	1.81e-04	-1.12e-01	0.0264
9620	CELSR1	CCI_1	Human	Cervix	CC	2.36e-20	1.57e+00	0.528
9620	CELSR1	CCI_2	Human	Cervix	CC	2.47e-03	4.05e-01	0.5249
9620	CELSR1	CCI_3	Human	Cervix	CC	1.66e-21	8.72e-01	0.516
9620	CELSR1	sample3	Human	Cervix	CC	2.83e-03	1.91e-01	0.1387
9620	CELSR1	AEH-subject1	Human	Endometrium	AEH	4.66e-09	3.57e-01	-0.3059
9620	CELSR1	AEH-subject3	Human	Endometrium	AEH	7.57e-08	3.66e-01	-0.2576
9620	CELSR1	AEH-subject5	Human	Endometrium	AEH	1.78e-21	6.42e-01	-0.2953
9620	CELSR1	EEC-subject2	Human	Endometrium	EEC	6.75e-13	4.51e-01	-0.2607
9620	CELSR1	EEC-subject4	Human	Endometrium	EEC	1.57e-02	2.78e-01	-0.2571
9620	CELSR1	EEC-subject5	Human	Endometrium	EEC	1.24e-05	2.99e-01	-0.249

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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

∗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:003297014	Breast	IDC	regulation of actin filament-based process	56/1434	397/18723	6.37e-06	1.99e-04	56
GO:003295614	Breast	IDC	regulation of actin cytoskeleton organization	48/1434	358/18723	1.03e-04	1.96e-03	48
GO:006056212	Breast	IDC	epithelial tube morphogenesis	44/1434	325/18723	1.58e-04	2.73e-03	44
GO:00303244	Breast	IDC	lung development	28/1434	177/18723	1.90e-04	3.15e-03	28
GO:00303234	Breast	IDC	respiratory tube development	28/1434	181/18723	2.78e-04	4.26e-03	28
GO:00611383	Breast	IDC	morphogenesis of a branching epithelium	28/1434	182/18723	3.05e-04	4.60e-03	28
GO:00605412	Breast	IDC	respiratory system development	30/1434	203/18723	3.85e-04	5.40e-03	30
GO:00017635	Breast	IDC	morphogenesis of a branching structure	29/1434	196/18723	4.68e-04	6.26e-03	29
GO:003514812	Breast	IDC	tube formation	23/1434	148/18723	8.79e-04	1.02e-02	23
GO:000183812	Breast	IDC	embryonic epithelial tube formation	19/1434	121/18723	2.10e-03	1.97e-02	19
GO:0048754	Breast	IDC	branching morphogenesis of an epithelial tube	22/1434	151/18723	2.61e-03	2.34e-02	22
GO:0060441	Breast	IDC	epithelial tube branching involved in lung morphogenesis	7/1434	29/18723	5.31e-03	3.94e-02	7
GO:00721756	Breast	IDC	epithelial tube formation	19/1434	132/18723	5.63e-03	4.08e-02	19
GO:003297024	Breast	DCIS	regulation of actin filament-based process	56/1390	397/18723	2.50e-06	8.74e-05	56
GO:003295624	Breast	DCIS	regulation of actin cytoskeleton organization	48/1390	358/18723	4.82e-05	9.92e-04	48
GO:003032413	Breast	DCIS	lung development	27/1390	177/18723	2.73e-04	4.09e-03	27
GO:003032313	Breast	DCIS	respiratory tube development	27/1390	181/18723	3.93e-04	5.41e-03	27
GO:006056221	Breast	DCIS	epithelial tube morphogenesis	41/1390	325/18723	5.98e-04	7.60e-03	41
GO:006054111	Breast	DCIS	respiratory system development	28/1390	203/18723	1.10e-03	1.19e-02	28
GO:006113811	Breast	DCIS	morphogenesis of a branching epithelium	25/1390	182/18723	2.08e-03	1.94e-02	25

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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

CELSR1

SNV

Missense_Mutation

rs73888514

c.4171N>A

p.Glu1391Lys

p.E1391K

Q9NYQ6

protein_coding

tolerated(0.08)

benign(0.425)

TCGA-3C-AALI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Poly E

Complete Response

CELSR1

SNV

Missense_Mutation

novel

c.8630G>A

p.Ser2877Asn

p.S2877N

Q9NYQ6

protein_coding

tolerated(0.32)

benign(0.05)

TCGA-A2-A4RW-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

CELSR1

SNV

Missense_Mutation

c.6920C>T

p.Thr2307Ile

p.T2307I

Q9NYQ6

protein_coding

tolerated(0.42)

benign(0.216)

TCGA-A8-A08R-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CELSR1

SNV

Missense_Mutation

rs146465806

c.8269N>A

p.Glu2757Lys

p.E2757K

Q9NYQ6

protein_coding

tolerated(0.09)

possibly_damaging(0.636)

TCGA-AC-A8OQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CELSR1

SNV

Missense_Mutation

rs143915949

c.8410N>A

p.Asp2804Asn

p.D2804N

Q9NYQ6

protein_coding

deleterious(0.01)

possibly_damaging(0.871)

TCGA-C8-A27B-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

CELSR1

SNV

Missense_Mutation

rs775423517

c.8191G>A

p.Ala2731Thr

p.A2731T

Q9NYQ6

protein_coding

tolerated(0.11)

benign(0.157)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

CELSR1

SNV

Missense_Mutation

novel

c.3998N>G

p.Ser1333Cys

p.S1333C

Q9NYQ6

protein_coding

deleterious(0)

probably_damaging(0.993)

TCGA-E9-A3QA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CELSR1

SNV

Missense_Mutation

c.860T>C

p.Leu287Pro

p.L287P

Q9NYQ6

protein_coding

deleterious(0.02)

probably_damaging(0.995)

TCGA-EW-A1P0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

CELSR1

insertion

Nonsense_Mutation

novel

c.5926_5927insTCGTGTCTCCAGAAATGCACACGCGTTCTCAGTGCAGACTCTAGGGA

p.Pro1976LeufsTer15

p.P1976Lfs*15

Q9NYQ6

protein_coding

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

CELSR1

insertion

Frame_Shift_Ins

novel

c.5313_5314insC

p.Gly1772ArgfsTer14

p.G1772Rfs*14

Q9NYQ6

protein_coding

TCGA-C8-A1HK-01

Breast

breast invasive 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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