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: CLSTN1

Gene summary for CLSTN1

Gene summary.

Gene information	Species	Human
	Gene symbol	CLSTN1
	Gene ID	22883
	Gene name	calsyntenin 1
	Gene Alias	ALC-ALPHA
	Cytomap	1p36.22
	Gene Type	protein-coding
	GO ID	GO:0001558
	UniProtAcc	O94985

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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
22883	CLSTN1	C07	Human	Oral cavity	OSCC	2.09e-04	1.12e+00	0.2491
22883	CLSTN1	C08	Human	Oral cavity	OSCC	1.81e-42	1.18e+00	0.1919
22883	CLSTN1	C09	Human	Oral cavity	OSCC	1.07e-20	8.94e-01	0.1431
22883	CLSTN1	LN22	Human	Oral cavity	OSCC	3.62e-22	2.19e+00	0.1733
22883	CLSTN1	LN46	Human	Oral cavity	OSCC	4.78e-16	8.44e-01	0.1666
22883	CLSTN1	LP15	Human	Oral cavity	LP	5.80e-18	2.48e+00	0.2174
22883	CLSTN1	LP17	Human	Oral cavity	LP	6.66e-13	2.72e+00	0.2349
22883	CLSTN1	SYSMH1	Human	Oral cavity	OSCC	9.29e-64	1.62e+00	0.1127
22883	CLSTN1	SYSMH2	Human	Oral cavity	OSCC	2.12e-32	1.23e+00	0.2326
22883	CLSTN1	SYSMH3	Human	Oral cavity	OSCC	6.50e-64	2.15e+00	0.2442
22883	CLSTN1	SYSMH4	Human	Oral cavity	OSCC	5.24e-07	2.32e-01	0.1226
22883	CLSTN1	SYSMH5	Human	Oral cavity	OSCC	5.77e-43	1.31e+00	0.0647
22883	CLSTN1	SYSMH6	Human	Oral cavity	OSCC	1.51e-14	7.22e-01	0.1275
22883	CLSTN1	GSM5252137_BPH556PrGA2_Fcol	Human	Prostate	BPH	8.96e-07	6.00e-01	-0.23
22883	CLSTN1	047563_1562-all-cells	Human	Prostate	BPH	1.44e-05	-5.99e-02	0.0791
22883	CLSTN1	048752_1579-all-cells	Human	Prostate	BPH	4.63e-02	2.64e-01	0.1008
22883	CLSTN1	052095_1628-all-cells	Human	Prostate	BPH	2.15e-02	2.49e-01	0.1032
22883	CLSTN1	052099_1652-all-cells	Human	Prostate	BPH	1.01e-05	3.59e-01	0.1038
22883	CLSTN1	Dong_P1	Human	Prostate	Tumor	3.27e-18	7.57e-02	0.035
22883	CLSTN1	Dong_P3	Human	Prostate	Tumor	1.10e-19	3.13e-01	0.0278

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
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
Prostate		BPH: Benign Prostatic Hyperplasia
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:19907788	Cervix	CC	protein localization to cell periphery	78/2311	333/18723	1.22e-08	9.73e-07	78
GO:00343298	Cervix	CC	cell junction assembly	88/2311	420/18723	3.42e-07	1.38e-05	88
GO:00160498	Cervix	CC	cell growth	92/2311	482/18723	1.16e-05	2.49e-04	92
GO:00988767	Cervix	CC	vesicle-mediated transport to the plasma membrane	34/2311	136/18723	3.75e-05	5.91e-04	34
GO:00901509	Cervix	CC	establishment of protein localization to membrane	54/2311	260/18723	7.67e-05	1.05e-03	54
GO:00015588	Cervix	CC	regulation of cell growth	77/2311	414/18723	1.40e-04	1.70e-03	77
GO:19018886	Cervix	CC	regulation of cell junction assembly	42/2311	204/18723	5.50e-04	5.29e-03	42
GO:00519603	Cervix	CC	regulation of nervous system development	77/2311	443/18723	1.13e-03	9.30e-03	77
GO:00519622	Cervix	CC	positive regulation of nervous system development	48/2311	272/18723	6.60e-03	3.65e-02	48
GO:1990778	Colorectum	AD	protein localization to cell periphery	129/3918	333/18723	5.51e-14	1.15e-11	129
GO:0090150	Colorectum	AD	establishment of protein localization to membrane	100/3918	260/18723	6.01e-11	6.33e-09	100
GO:0034329	Colorectum	AD	cell junction assembly	136/3918	420/18723	2.02e-08	1.15e-06	136
GO:0098876	Colorectum	AD	vesicle-mediated transport to the plasma membrane	57/3918	136/18723	2.30e-08	1.27e-06	57
GO:0016049	Colorectum	AD	cell growth	143/3918	482/18723	2.83e-06	8.09e-05	143
GO:0001558	Colorectum	AD	regulation of cell growth	124/3918	414/18723	7.67e-06	1.86e-04	124
GO:1901888	Colorectum	AD	regulation of cell junction assembly	61/3918	204/18723	1.50e-03	1.27e-02	61
GO:0050808	Colorectum	AD	synapse organization	112/3918	426/18723	4.25e-03	2.92e-02	112
GO:1902414	Colorectum	AD	protein localization to cell junction	31/3918	94/18723	4.30e-03	2.95e-02	31
GO:0050807	Colorectum	AD	regulation of synapse organization	60/3918	211/18723	5.67e-03	3.64e-02	60
GO:0099072	Colorectum	AD	regulation of postsynaptic membrane neurotransmitter receptor levels	22/3918	62/18723	5.72e-03	3.64e-02	22

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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

CLSTN1

SNV

Missense_Mutation

rs751480577

c.1498N>A

p.Val500Met

p.V500M

O94985

protein_coding

tolerated(0.35)

probably_damaging(0.942)

TCGA-A2-A3XV-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

CLSTN1

SNV

Missense_Mutation

rs201194236

c.2146N>A

p.Asp716Asn

p.D716N

O94985

protein_coding

tolerated(1)

benign(0.003)

TCGA-BH-A0HP-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

doxorubicin

CLSTN1

SNV

Missense_Mutation

rs749257979

c.2896N>A

p.Ala966Thr

p.A966T

O94985

protein_coding

tolerated(0.32)

benign(0.001)

TCGA-D8-A1JA-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

CLSTN1

SNV

Missense_Mutation

c.1270N>T

p.Gly424Trp

p.G424W

O94985

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-EW-A6S9-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CLSTN1

insertion

Frame_Shift_Ins

novel

c.1656dupG

p.Lys553GlufsTer48

p.K553Efs*48

O94985

protein_coding

TCGA-BH-A0DP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

CLSTN1

insertion

In_Frame_Ins

novel

c.1654_1655insCGCCAGTGCTTCCCAAACGACCCATGGGGA

p.Asp551_Lys552insThrProValLeuProLysArgProMetGly

p.D551_K552insTPVLPKRPMG

O94985

protein_coding

TCGA-BH-A0DP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

CLSTN1

insertion

Frame_Shift_Ins

novel

c.774_775insG

p.Pro259AlafsTer15

p.P259Afs*15

O94985

protein_coding

TCGA-BH-A0H7-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

doxorubicin

CLSTN1

insertion

Frame_Shift_Ins

novel

c.772_773insGACAGAGTCTCACTCTGTCACCC

p.Lys258ArgfsTer56

p.K258Rfs*56

O94985

protein_coding

TCGA-BH-A0H7-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

doxorubicin

CLSTN1

deletion

Frame_Shift_Del

novel

c.755delT

p.Leu252TrpfsTer2

p.L252Wfs*2

O94985

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

CLSTN1

SNV

Missense_Mutation

rs778535987

c.709G>A

p.Val237Ile

p.V237I

O94985

protein_coding

tolerated(0.07)

probably_damaging(0.997)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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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