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: ITSN2

Gene summary for ITSN2

Gene summary.

Gene information	Species	Human
	Gene symbol	ITSN2
	Gene ID	50618
	Gene name	intersectin 2
	Gene Alias	PRO2015
	Cytomap	2p23.3
	Gene Type	protein-coding
	GO ID	GO:0000902
	UniProtAcc	A6H8W8

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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
50618	ITSN2	CA_HPV_1	Human	Cervix	CC	4.29e-03	1.37e-02	0.0264
50618	ITSN2	CCI_2	Human	Cervix	CC	2.54e-06	9.01e-01	0.5249
50618	ITSN2	CCI_3	Human	Cervix	CC	7.35e-04	6.89e-01	0.516
50618	ITSN2	HTA11_3410_2000001011	Human	Colorectum	AD	9.17e-04	-4.13e-01	0.0155
50618	ITSN2	HTA11_866_3004761011	Human	Colorectum	AD	7.54e-07	-4.23e-01	0.096
50618	ITSN2	HTA11_7696_3000711011	Human	Colorectum	AD	1.70e-04	-3.35e-01	0.0674
50618	ITSN2	HTA11_99999970781_79442	Human	Colorectum	MSS	3.14e-03	-2.99e-01	0.294
50618	ITSN2	HTA11_99999974143_84620	Human	Colorectum	MSS	8.54e-06	-3.30e-01	0.3005
50618	ITSN2	A002-C-010	Human	Colorectum	FAP	1.78e-02	-1.46e-01	0.242
50618	ITSN2	A001-C-207	Human	Colorectum	FAP	1.48e-02	-1.48e-01	0.1278
50618	ITSN2	A015-C-203	Human	Colorectum	FAP	2.32e-28	-3.54e-01	-0.1294
50618	ITSN2	A015-C-204	Human	Colorectum	FAP	5.37e-05	-2.47e-01	-0.0228
50618	ITSN2	A014-C-040	Human	Colorectum	FAP	1.49e-04	-5.16e-01	-0.1184
50618	ITSN2	A002-C-201	Human	Colorectum	FAP	6.84e-13	-3.78e-01	0.0324
50618	ITSN2	A002-C-203	Human	Colorectum	FAP	1.26e-03	-1.45e-01	0.2786
50618	ITSN2	A001-C-119	Human	Colorectum	FAP	2.75e-05	-5.17e-02	-0.1557
50618	ITSN2	A001-C-108	Human	Colorectum	FAP	1.71e-15	-1.34e-01	-0.0272
50618	ITSN2	A002-C-205	Human	Colorectum	FAP	3.15e-19	-3.48e-01	-0.1236
50618	ITSN2	A001-C-104	Human	Colorectum	FAP	3.24e-02	-3.89e-02	0.0184
50618	ITSN2	A015-C-005	Human	Colorectum	FAP	2.84e-04	-3.20e-01	-0.0336

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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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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
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
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:002260410	Cervix	CC	regulation of cell morphogenesis	84/2311	309/18723	1.00e-12	4.29e-10	84
GO:00160498	Cervix	CC	cell growth	92/2311	482/18723	1.16e-05	2.49e-04	92
GO:00068987	Cervix	CC	receptor-mediated endocytosis	53/2311	244/18723	2.52e-05	4.29e-04	53
GO:00725836	Cervix	CC	clathrin-dependent endocytosis	16/2311	47/18723	9.56e-05	1.25e-03	16
GO:00459277	Cervix	CC	positive regulation of growth	53/2311	259/18723	1.33e-04	1.64e-03	53
GO:00015588	Cervix	CC	regulation of cell growth	77/2311	414/18723	1.40e-04	1.70e-03	77
GO:00161977	Cervix	CC	endosomal transport	48/2311	230/18723	1.65e-04	1.97e-03	48
GO:00995322	Cervix	CC	synaptic vesicle endosomal processing	6/2311	10/18723	4.73e-04	4.68e-03	6
GO:00303077	Cervix	CC	positive regulation of cell growth	36/2311	166/18723	4.84e-04	4.75e-03	36
GO:00486386	Cervix	CC	regulation of developmental growth	61/2311	330/18723	7.69e-04	6.85e-03	61
GO:00605606	Cervix	CC	developmental growth involved in morphogenesis	46/2311	234/18723	8.82e-04	7.63e-03	46
GO:00484883	Cervix	CC	synaptic vesicle endocytosis	16/2311	62/18723	2.87e-03	1.91e-02	16
GO:01402383	Cervix	CC	presynaptic endocytosis	16/2311	62/18723	2.87e-03	1.91e-02	16
GO:19901385	Cervix	CC	neuron projection extension	34/2311	172/18723	3.52e-03	2.27e-02	34
GO:00486395	Cervix	CC	positive regulation of developmental growth	33/2311	174/18723	7.65e-03	4.07e-02	33
GO:00485886	Cervix	CC	developmental cell growth	42/2311	234/18723	7.88e-03	4.15e-02	42
GO:00364655	Cervix	CC	synaptic vesicle recycling	17/2311	75/18723	8.87e-03	4.53e-02	17
GO:0016197	Colorectum	AD	endosomal transport	90/3918	230/18723	1.88e-10	1.73e-08	90
GO:0022604	Colorectum	AD	regulation of cell morphogenesis	109/3918	309/18723	3.08e-09	2.07e-07	109
GO:0016049	Colorectum	AD	cell growth	143/3918	482/18723	2.83e-06	8.09e-05	143

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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

ITSN2

SNV

Missense_Mutation

c.700N>T

p.Gly234Trp

p.G234W

Q9NZM3

protein_coding

deleterious(0)

probably_damaging(0.971)

TCGA-A8-A08L-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

ITSN2

SNV

Missense_Mutation

c.4803N>C

p.Gln1601His

p.Q1601H

Q9NZM3

protein_coding

deleterious(0.01)

probably_damaging(0.999)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ITSN2

SNV

Missense_Mutation

c.707N>T

p.Ser236Leu

p.S236L

Q9NZM3

protein_coding

tolerated(0.16)

benign(0.141)

TCGA-BH-A0HL-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

ITSN2

SNV

Missense_Mutation

c.2516N>G

p.Ser839Cys

p.S839C

Q9NZM3

protein_coding

deleterious(0.03)

benign(0.286)

TCGA-C8-A12Q-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

ITSN2

SNV

Missense_Mutation

c.3047N>T

p.Glu1016Val

p.E1016V

Q9NZM3

protein_coding

deleterious(0)

possibly_damaging(0.857)

TCGA-C8-A1HJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ITSN2

SNV

Missense_Mutation

c.338N>A

p.Ile113Asn

p.I113N

Q9NZM3

protein_coding

tolerated(0.2)

benign(0.105)

TCGA-C8-A26Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ITSN2

SNV

Missense_Mutation

novel

c.3318N>T

p.Trp1106Cys

p.W1106C

Q9NZM3

protein_coding

deleterious(0)

benign(0.157)

TCGA-D8-A1JK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ITSN2

SNV

Missense_Mutation

c.335N>C

p.Leu112Ser

p.L112S

Q9NZM3

protein_coding

tolerated(0.66)

benign(0.124)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

ITSN2

SNV

Missense_Mutation

c.2203N>C

p.Ala735Pro

p.A735P

Q9NZM3

protein_coding

tolerated(0.32)

benign(0.043)

TCGA-D8-A27F-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin+cyclophosphamide

ITSN2

SNV

Missense_Mutation

c.2359G>A

p.Asp787Asn

p.D787N

Q9NZM3

protein_coding

deleterious(0.04)

possibly_damaging(0.836)

TCGA-E2-A159-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

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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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