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: SYVN1

Gene summary for SYVN1

Gene summary.

Gene information	Species	Human
	Gene symbol	SYVN1
	Gene ID	84447
	Gene name	synoviolin 1
	Gene Alias	DER3
	Cytomap	11q13.1
	Gene Type	protein-coding
	GO ID	GO:0000209
	UniProtAcc	Q86TM6

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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
84447	SYVN1	LZE4T	Human	Esophagus	ESCC	2.68e-09	1.64e-01	0.0811
84447	SYVN1	LZE7T	Human	Esophagus	ESCC	6.56e-07	4.90e-01	0.0667
84447	SYVN1	LZE8T	Human	Esophagus	ESCC	5.37e-09	1.77e-01	0.067
84447	SYVN1	LZE20T	Human	Esophagus	ESCC	3.22e-08	1.63e-01	0.0662
84447	SYVN1	LZE21D1	Human	Esophagus	HGIN	2.98e-02	2.09e-01	0.0632
84447	SYVN1	LZE22D1	Human	Esophagus	HGIN	1.27e-08	3.85e-01	0.0595
84447	SYVN1	LZE22T	Human	Esophagus	ESCC	2.76e-08	5.86e-01	0.068
84447	SYVN1	LZE24T	Human	Esophagus	ESCC	3.30e-20	4.89e-01	0.0596
84447	SYVN1	LZE21T	Human	Esophagus	ESCC	5.80e-04	3.20e-01	0.0655
84447	SYVN1	P1T-E	Human	Esophagus	ESCC	4.15e-07	3.91e-01	0.0875
84447	SYVN1	P2T-E	Human	Esophagus	ESCC	1.82e-19	2.73e-01	0.1177
84447	SYVN1	P4T-E	Human	Esophagus	ESCC	1.33e-14	3.38e-01	0.1323
84447	SYVN1	P5T-E	Human	Esophagus	ESCC	1.32e-10	8.09e-02	0.1327
84447	SYVN1	P8T-E	Human	Esophagus	ESCC	6.27e-22	3.50e-01	0.0889
84447	SYVN1	P9T-E	Human	Esophagus	ESCC	4.31e-10	1.27e-01	0.1131
84447	SYVN1	P10T-E	Human	Esophagus	ESCC	6.12e-21	3.71e-01	0.116
84447	SYVN1	P11T-E	Human	Esophagus	ESCC	3.12e-14	4.97e-01	0.1426
84447	SYVN1	P12T-E	Human	Esophagus	ESCC	1.17e-21	2.44e-01	0.1122
84447	SYVN1	P15T-E	Human	Esophagus	ESCC	1.04e-18	3.32e-01	0.1149
84447	SYVN1	P16T-E	Human	Esophagus	ESCC	2.45e-21	3.86e-01	0.1153

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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

∗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:001049826	Esophagus	HGIN	proteasomal protein catabolic process	139/2587	490/18723	1.20e-17	3.41e-15	139
GO:003164727	Esophagus	HGIN	regulation of protein stability	96/2587	298/18723	2.21e-16	5.76e-14	96
GO:009719327	Esophagus	HGIN	intrinsic apoptotic signaling pathway	90/2587	288/18723	1.50e-14	2.80e-12	90
GO:004316126	Esophagus	HGIN	proteasome-mediated ubiquitin-dependent protein catabolic process	114/2587	412/18723	7.00e-14	1.20e-11	114
GO:003497625	Esophagus	HGIN	response to endoplasmic reticulum stress	81/2587	256/18723	1.47e-13	2.32e-11	81
GO:200124227	Esophagus	HGIN	regulation of intrinsic apoptotic signaling pathway	58/2587	164/18723	2.57e-12	3.58e-10	58
GO:005082127	Esophagus	HGIN	protein stabilization	64/2587	191/18723	3.11e-12	4.24e-10	64
GO:200123327	Esophagus	HGIN	regulation of apoptotic signaling pathway	97/2587	356/18723	1.36e-11	1.57e-09	97
GO:190589725	Esophagus	HGIN	regulation of response to endoplasmic reticulum stress	31/2587	82/18723	5.25e-08	2.91e-06	31
GO:007005920	Esophagus	HGIN	intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	25/2587	63/18723	3.41e-07	1.57e-05	25
GO:200123427	Esophagus	HGIN	negative regulation of apoptotic signaling pathway	59/2587	224/18723	4.68e-07	2.07e-05	59
GO:200124325	Esophagus	HGIN	negative regulation of intrinsic apoptotic signaling pathway	33/2587	98/18723	4.73e-07	2.07e-05	33
GO:007093610	Esophagus	HGIN	protein K48-linked ubiquitination	24/2587	65/18723	2.69e-06	9.49e-05	24
GO:000020916	Esophagus	HGIN	protein polyubiquitination	58/2587	236/18723	6.29e-06	1.97e-04	58
GO:19022359	Esophagus	HGIN	regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	15/2587	32/18723	6.76e-06	2.08e-04	15
GO:190357320	Esophagus	HGIN	negative regulation of response to endoplasmic reticulum stress	18/2587	44/18723	8.97e-06	2.64e-04	18
GO:190223620	Esophagus	HGIN	negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	11/2587	20/18723	1.73e-05	4.71e-04	11
GO:00309706	Esophagus	HGIN	retrograde protein transport, ER to cytosol	12/2587	29/18723	2.48e-04	4.38e-03	12
GO:19035136	Esophagus	HGIN	endoplasmic reticulum to cytosol transport	12/2587	29/18723	2.48e-04	4.38e-03	12
GO:00365036	Esophagus	HGIN	ERAD pathway	27/2587	107/18723	1.15e-03	1.39e-02	27

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0414139	Esophagus	HGIN	Protein processing in endoplasmic reticulum	67/1383	174/8465	1.06e-12	2.16e-11	1.72e-11	67
hsa0412026	Esophagus	HGIN	Ubiquitin mediated proteolysis	49/1383	142/8465	7.78e-08	1.33e-06	1.06e-06	49
hsa04141114	Esophagus	HGIN	Protein processing in endoplasmic reticulum	67/1383	174/8465	1.06e-12	2.16e-11	1.72e-11	67
hsa04120111	Esophagus	HGIN	Ubiquitin mediated proteolysis	49/1383	142/8465	7.78e-08	1.33e-06	1.06e-06	49
hsa04141211	Esophagus	ESCC	Protein processing in endoplasmic reticulum	147/4205	174/8465	3.29e-22	1.10e-19	5.64e-20	147
hsa0412027	Esophagus	ESCC	Ubiquitin mediated proteolysis	122/4205	142/8465	6.53e-20	7.29e-18	3.74e-18	122
hsa04141310	Esophagus	ESCC	Protein processing in endoplasmic reticulum	147/4205	174/8465	3.29e-22	1.10e-19	5.64e-20	147
hsa0412036	Esophagus	ESCC	Ubiquitin mediated proteolysis	122/4205	142/8465	6.53e-20	7.29e-18	3.74e-18	122
hsa0414114	Liver	Cirrhotic	Protein processing in endoplasmic reticulum	114/2530	174/8465	1.16e-22	9.67e-21	5.96e-21	114
hsa0412021	Liver	Cirrhotic	Ubiquitin mediated proteolysis	72/2530	142/8465	1.32e-07	1.97e-06	1.21e-06	72
hsa0414115	Liver	Cirrhotic	Protein processing in endoplasmic reticulum	114/2530	174/8465	1.16e-22	9.67e-21	5.96e-21	114
hsa0412031	Liver	Cirrhotic	Ubiquitin mediated proteolysis	72/2530	142/8465	1.32e-07	1.97e-06	1.21e-06	72
hsa0414122	Liver	HCC	Protein processing in endoplasmic reticulum	146/4020	174/8465	7.34e-24	2.46e-21	1.37e-21	146
hsa0412041	Liver	HCC	Ubiquitin mediated proteolysis	110/4020	142/8465	1.67e-13	3.74e-12	2.08e-12	110
hsa0414132	Liver	HCC	Protein processing in endoplasmic reticulum	146/4020	174/8465	7.34e-24	2.46e-21	1.37e-21	146
hsa0412051	Liver	HCC	Ubiquitin mediated proteolysis	110/4020	142/8465	1.67e-13	3.74e-12	2.08e-12	110
hsa0414130	Oral cavity	OSCC	Protein processing in endoplasmic reticulum	143/3704	174/8465	6.82e-26	2.28e-23	1.16e-23	143
hsa0412020	Oral cavity	OSCC	Ubiquitin mediated proteolysis	105/3704	142/8465	1.83e-13	4.37e-12	2.23e-12	105
hsa04141113	Oral cavity	OSCC	Protein processing in endoplasmic reticulum	143/3704	174/8465	6.82e-26	2.28e-23	1.16e-23	143
hsa04120110	Oral cavity	OSCC	Ubiquitin mediated proteolysis	105/3704	142/8465	1.83e-13	4.37e-12	2.23e-12	105

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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

SYVN1

SNV

Missense_Mutation

c.539N>C

p.Ile180Thr

p.I180T

Q86TM6

protein_coding

deleterious(0)

probably_damaging(0.94)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SYVN1

SNV

Missense_Mutation

c.1339N>C

p.Glu447Gln

p.E447Q

Q86TM6

protein_coding

tolerated(0.62)

benign(0.031)

TCGA-B6-A0X5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SYVN1

SNV

Missense_Mutation

rs780751856

c.1489C>T

p.Arg497Trp

p.R497W

Q86TM6

protein_coding

deleterious(0)

benign(0.295)

TCGA-BH-A0BJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

SYVN1

insertion

Nonsense_Mutation

novel

c.270_271insTACACTTGAAAATGGAATGGAATCT

p.Ala91TyrfsTer3

p.A91Yfs*3

Q86TM6

protein_coding

TCGA-A8-A06P-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unspecific

SYVN1

insertion

In_Frame_Ins

novel

c.921_922insCCCCCATGG

p.Cys307_Asn308insProProTrp

p.C307_N308insPPW

Q86TM6

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SYVN1

insertion

Frame_Shift_Ins

novel

c.919_920insCCTTTTCCTCCAGGCATGTTCCCACTGTG

p.Cys307SerfsTer188

p.C307Sfs*188

Q86TM6

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SYVN1

SNV

Missense_Mutation

novel

c.185N>A

p.Gly62Asp

p.G62D

Q86TM6

protein_coding

tolerated(0.05)

benign(0.428)

TCGA-C5-A902-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SYVN1

insertion

Frame_Shift_Ins

novel

c.1203_1204insTG

p.Glu402TrpfsTer84

p.E402Wfs*84

Q86TM6

protein_coding

TCGA-DS-A1OD-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SYVN1

SNV

Missense_Mutation

c.755N>C

p.Met252Thr

p.M252T

Q86TM6

protein_coding

deleterious(0)

benign(0.316)

TCGA-AA-3492-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

SYVN1

SNV

Missense_Mutation

c.566N>G

p.Phe189Cys

p.F189C

Q86TM6

protein_coding

tolerated(0.07)

possibly_damaging(0.829)

TCGA-AA-3681-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

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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