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: SYNE2

Gene summary for SYNE2

Gene summary.

Gene information	Species	Human
	Gene symbol	SYNE2
	Gene ID	23224
	Gene name	spectrin repeat containing nuclear envelope protein 2
	Gene Alias	EDMD5
	Cytomap	14q23.2
	Gene Type	protein-coding
	GO ID	GO:0006810
	UniProtAcc	Q8WXH0

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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
23224	SYNE2	GSM4909285	Human	Breast	IDC	8.80e-03	9.01e-02	0.21
23224	SYNE2	GSM4909296	Human	Breast	IDC	9.69e-06	-3.00e-01	0.1524
23224	SYNE2	GSM4909297	Human	Breast	IDC	3.76e-06	-3.07e-01	0.1517
23224	SYNE2	GSM4909301	Human	Breast	IDC	1.83e-08	-3.32e-01	0.1577
23224	SYNE2	GSM4909302	Human	Breast	IDC	3.46e-02	-2.58e-01	0.1545
23224	SYNE2	GSM4909306	Human	Breast	IDC	4.42e-05	-3.29e-01	0.1564
23224	SYNE2	GSM4909311	Human	Breast	IDC	2.32e-14	-3.54e-01	0.1534
23224	SYNE2	GSM4909312	Human	Breast	IDC	6.16e-10	-3.58e-01	0.1552
23224	SYNE2	GSM4909319	Human	Breast	IDC	1.51e-18	-3.86e-01	0.1563
23224	SYNE2	GSM4909320	Human	Breast	IDC	7.91e-03	-3.47e-01	0.1575
23224	SYNE2	GSM4909321	Human	Breast	IDC	4.22e-14	-3.73e-01	0.1559
23224	SYNE2	NCCBC14	Human	Breast	DCIS	6.38e-05	-2.08e-01	0.2021
23224	SYNE2	NCCBC5	Human	Breast	DCIS	2.40e-08	-2.37e-01	0.2046
23224	SYNE2	P1	Human	Breast	IDC	4.14e-18	3.79e-01	0.1527
23224	SYNE2	DCIS2	Human	Breast	DCIS	4.45e-71	7.42e-01	0.0085
23224	SYNE2	CA_HPV_1	Human	Cervix	CC	5.47e-07	-4.56e-01	0.0264
23224	SYNE2	CA_HPV_2	Human	Cervix	CC	2.48e-07	4.05e-01	0.0391
23224	SYNE2	CA_HPV_3	Human	Cervix	CC	9.25e-10	2.18e-01	0.0414
23224	SYNE2	HSIL_HPV_1	Human	Cervix	HSIL_HPV	3.24e-04	-3.58e-01	0.0116
23224	SYNE2	N_HPV_1	Human	Cervix	N_HPV	1.06e-04	-4.48e-01	0.0079

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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
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
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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
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:00516567	Cervix	CC	establishment of organelle localization	76/2311	390/18723	3.17e-05	5.21e-04	76
GO:00300487	Cervix	CC	actin filament-based movement	29/2311	127/18723	6.91e-04	6.33e-03	29
GO:00307057	Cervix	CC	cytoskeleton-dependent intracellular transport	40/2311	195/18723	7.92e-04	6.99e-03	40
GO:00618425	Cervix	CC	microtubule organizing center localization	11/2311	33/18723	1.42e-03	1.11e-02	11
GO:00995157	Cervix	CC	actin filament-based transport	8/2311	21/18723	2.44e-03	1.71e-02	8
GO:00516425	Cervix	CC	centrosome localization	10/2311	32/18723	3.96e-03	2.48e-02	10
GO:003004813	Cervix	HSIL_HPV	actin filament-based movement	12/737	127/18723	4.37e-03	3.68e-02	12
GO:006184212	Cervix	N_HPV	microtubule organizing center localization	6/534	33/18723	3.01e-04	4.64e-03	6
GO:005164211	Cervix	N_HPV	centrosome localization	5/534	32/18723	1.97e-03	1.93e-02	5
GO:003070513	Cervix	N_HPV	cytoskeleton-dependent intracellular transport	13/534	195/18723	4.03e-03	3.16e-02	13
GO:0051656	Colorectum	AD	establishment of organelle localization	131/3918	390/18723	3.00e-09	2.06e-07	131
GO:0030048	Colorectum	AD	actin filament-based movement	44/3918	127/18723	2.31e-04	2.99e-03	44
GO:0099515	Colorectum	AD	actin filament-based transport	12/3918	21/18723	3.02e-04	3.62e-03	12
GO:0030705	Colorectum	AD	cytoskeleton-dependent intracellular transport	60/3918	195/18723	7.56e-04	7.59e-03	60
GO:0007097	Colorectum	AD	nuclear migration	10/3918	20/18723	3.67e-03	2.60e-02	10
GO:0051647	Colorectum	AD	nucleus localization	11/3918	24/18723	5.43e-03	3.55e-02	11
GO:00516561	Colorectum	SER	establishment of organelle localization	100/2897	390/18723	1.11e-07	6.79e-06	100
GO:00300481	Colorectum	SER	actin filament-based movement	38/2897	127/18723	2.80e-05	7.56e-04	38
GO:00995151	Colorectum	SER	actin filament-based transport	11/2897	21/18723	9.28e-05	1.98e-03	11
GO:00307051	Colorectum	SER	cytoskeleton-dependent intracellular transport	44/2897	195/18723	5.53e-03	4.09e-02	44

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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

SYNE2

SNV

Missense_Mutation

c.13049C>T

p.Ser4350Leu

p.S4350L

Q8WXH0

protein_coding

tolerated(0.06)

benign(0.015)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

SYNE2

SNV

Missense_Mutation

c.13813G>C

p.Glu4605Gln

p.E4605Q

Q8WXH0

protein_coding

tolerated(0.23)

benign(0.107)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

SYNE2

SNV

Missense_Mutation

novel

c.18166G>C

p.Asp6056His

p.D6056H

Q8WXH0

protein_coding

deleterious(0)

benign(0.364)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

SYNE2

SNV

Missense_Mutation

c.5643N>G

p.Phe1881Leu

p.F1881L

Q8WXH0

protein_coding

deleterious(0.01)

possibly_damaging(0.808)

TCGA-A2-A0CR-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

SYNE2

SNV

Missense_Mutation

c.3278N>T

p.Ser1093Leu

p.S1093L

Q8WXH0

protein_coding

deleterious(0.03)

benign(0.027)

TCGA-A2-A0EQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

SYNE2

SNV

Missense_Mutation

c.15141N>G

p.Ile5047Met

p.I5047M

Q8WXH0

protein_coding

deleterious(0)

probably_damaging(0.935)

TCGA-A2-A1FW-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

SYNE2

SNV

Missense_Mutation

novel

c.11789G>T

p.Gly3930Val

p.G3930V

Q8WXH0

protein_coding

deleterious(0.01)

probably_damaging(0.996)

TCGA-A7-A0DB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

SYNE2

SNV

Missense_Mutation

c.12647C>G

p.Ser4216Cys

p.S4216C

Q8WXH0

protein_coding

tolerated(0.18)

possibly_damaging(0.614)

TCGA-A7-A0DB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

SYNE2

SNV

Missense_Mutation

novel

c.17066G>T

p.Arg5689Leu

p.R5689L

Q8WXH0

protein_coding

deleterious(0.03)

benign(0.036)

TCGA-A7-A0DB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

SYNE2

SNV

Missense_Mutation

novel

c.15958N>A

p.Leu5320Ile

p.L5320I

Q8WXH0

protein_coding

deleterious(0)

probably_damaging(0.988)

TCGA-A7-A26I-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

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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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