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: SVIP

Gene summary for SVIP

Gene summary.

Gene information	Species	Human
	Gene symbol	SVIP
	Gene ID	258010
	Gene name	small VCP interacting protein
	Gene Alias	SVIP
	Cytomap	11p14.3
	Gene Type	protein-coding
	GO ID	GO:0006464
	UniProtAcc	Q8NHG7

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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
258010	SVIP	LZE7T	Human	Esophagus	ESCC	2.77e-09	3.30e-01	0.0667
258010	SVIP	LZE22T	Human	Esophagus	ESCC	2.23e-03	4.01e-03	0.068
258010	SVIP	LZE24T	Human	Esophagus	ESCC	7.34e-09	1.50e-01	0.0596
258010	SVIP	LZE6T	Human	Esophagus	ESCC	1.58e-07	3.28e-03	0.0845
258010	SVIP	P2T-E	Human	Esophagus	ESCC	5.01e-10	-2.37e-02	0.1177
258010	SVIP	P4T-E	Human	Esophagus	ESCC	4.19e-02	-2.33e-01	0.1323
258010	SVIP	P5T-E	Human	Esophagus	ESCC	8.40e-12	1.20e-01	0.1327
258010	SVIP	P8T-E	Human	Esophagus	ESCC	2.40e-13	1.22e-01	0.0889
258010	SVIP	P9T-E	Human	Esophagus	ESCC	1.94e-02	-1.61e-01	0.1131
258010	SVIP	P10T-E	Human	Esophagus	ESCC	6.81e-14	1.92e-01	0.116
258010	SVIP	P11T-E	Human	Esophagus	ESCC	5.54e-07	4.67e-02	0.1426
258010	SVIP	P15T-E	Human	Esophagus	ESCC	9.01e-03	-2.35e-01	0.1149
258010	SVIP	P16T-E	Human	Esophagus	ESCC	2.23e-04	2.01e-02	0.1153
258010	SVIP	P20T-E	Human	Esophagus	ESCC	2.27e-02	-2.34e-01	0.1124
258010	SVIP	P22T-E	Human	Esophagus	ESCC	9.86e-07	5.49e-03	0.1236
258010	SVIP	P23T-E	Human	Esophagus	ESCC	5.37e-03	-1.99e-01	0.108
258010	SVIP	P24T-E	Human	Esophagus	ESCC	6.60e-03	-2.10e-02	0.1287
258010	SVIP	P26T-E	Human	Esophagus	ESCC	6.13e-07	-3.38e-02	0.1276
258010	SVIP	P27T-E	Human	Esophagus	ESCC	2.72e-08	-6.16e-03	0.1055
258010	SVIP	P28T-E	Human	Esophagus	ESCC	2.98e-11	1.73e-01	0.1149

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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
Prostate		BPH: Benign Prostatic Hyperplasia
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:0010498111	Esophagus	ESCC	proteasomal protein catabolic process	369/8552	490/18723	1.13e-41	1.80e-38	369
GO:0043161111	Esophagus	ESCC	proteasome-mediated ubiquitin-dependent protein catabolic process	312/8552	412/18723	3.53e-36	4.48e-33	312
GO:0042176111	Esophagus	ESCC	regulation of protein catabolic process	280/8552	391/18723	8.65e-26	2.39e-23	280
GO:003238618	Esophagus	ESCC	regulation of intracellular transport	243/8552	337/18723	3.20e-23	7.25e-21	243
GO:0009896111	Esophagus	ESCC	positive regulation of catabolic process	332/8552	492/18723	4.36e-23	9.22e-21	332
GO:0034976111	Esophagus	ESCC	response to endoplasmic reticulum stress	192/8552	256/18723	7.15e-22	1.30e-19	192
GO:0031331111	Esophagus	ESCC	positive regulation of cellular catabolic process	292/8552	427/18723	8.67e-22	1.53e-19	292
GO:1903362111	Esophagus	ESCC	regulation of cellular protein catabolic process	188/8552	255/18723	5.12e-20	6.62e-18	188
GO:0033157110	Esophagus	ESCC	regulation of intracellular protein transport	169/8552	229/18723	3.31e-18	3.23e-16	169
GO:001050617	Esophagus	ESCC	regulation of autophagy	220/8552	317/18723	6.72e-18	6.36e-16	220
GO:1903050111	Esophagus	ESCC	regulation of proteolysis involved in cellular protein catabolic process	163/8552	221/18723	1.44e-17	1.27e-15	163
GO:0061136111	Esophagus	ESCC	regulation of proteasomal protein catabolic process	142/8552	187/18723	2.40e-17	2.00e-15	142
GO:0043254111	Esophagus	ESCC	regulation of protein-containing complex assembly	278/8552	428/18723	3.81e-16	2.77e-14	278
GO:0032434111	Esophagus	ESCC	regulation of proteasomal ubiquitin-dependent protein catabolic process	107/8552	134/18723	4.06e-16	2.93e-14	107
GO:2000058111	Esophagus	ESCC	regulation of ubiquitin-dependent protein catabolic process	125/8552	164/18723	1.17e-15	7.76e-14	125
GO:003650315	Esophagus	ESCC	ERAD pathway	82/8552	107/18723	5.80e-11	1.84e-09	82
GO:0009895111	Esophagus	ESCC	negative regulation of catabolic process	201/8552	320/18723	3.88e-10	1.05e-08	201
GO:003043314	Esophagus	ESCC	ubiquitin-dependent ERAD pathway	66/8552	85/18723	1.64e-09	3.78e-08	66
GO:0031330111	Esophagus	ESCC	negative regulation of cellular catabolic process	166/8552	262/18723	5.17e-09	1.08e-07	166
GO:1905897111	Esophagus	ESCC	regulation of response to endoplasmic reticulum stress	63/8552	82/18723	8.16e-09	1.66e-07	63

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa04141211	Esophagus	ESCC	Protein processing in endoplasmic reticulum	147/4205	174/8465	3.29e-22	1.10e-19	5.64e-20	147
hsa04141310	Esophagus	ESCC	Protein processing in endoplasmic reticulum	147/4205	174/8465	3.29e-22	1.10e-19	5.64e-20	147
hsa0414114	Liver	Cirrhotic	Protein processing in endoplasmic reticulum	114/2530	174/8465	1.16e-22	9.67e-21	5.96e-21	114
hsa0414115	Liver	Cirrhotic	Protein processing in endoplasmic reticulum	114/2530	174/8465	1.16e-22	9.67e-21	5.96e-21	114
hsa0414122	Liver	HCC	Protein processing in endoplasmic reticulum	146/4020	174/8465	7.34e-24	2.46e-21	1.37e-21	146
hsa0414132	Liver	HCC	Protein processing in endoplasmic reticulum	146/4020	174/8465	7.34e-24	2.46e-21	1.37e-21	146
hsa0414128	Prostate	BPH	Protein processing in endoplasmic reticulum	97/1718	174/8465	2.37e-25	1.30e-23	8.07e-24	97
hsa04141112	Prostate	BPH	Protein processing in endoplasmic reticulum	97/1718	174/8465	2.37e-25	1.30e-23	8.07e-24	97
hsa0414129	Prostate	Tumor	Protein processing in endoplasmic reticulum	99/1791	174/8465	2.58e-25	1.71e-23	1.06e-23	99
hsa0414137	Prostate	Tumor	Protein processing in endoplasmic reticulum	99/1791	174/8465	2.58e-25	1.71e-23	1.06e-23	99

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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

SVIP

insertion

Frame_Shift_Ins

rs760679527

c.169_170insA

p.Ile57AsnfsTer17

p.I57Nfs*17

Q8NHG7

protein_coding

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SVIP

insertion

Nonsense_Mutation

novel

c.74_75insGAACTTTTAGCAATATATAATTAGTTTCAATATAAGGTAAATA

p.Ala26AsnfsTer3

p.A26Nfs*3

Q8NHG7

protein_coding

TCGA-AN-A0FS-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SVIP

SNV

Missense_Mutation

c.162N>T

p.Lys54Asn

p.K54N

Q8NHG7

protein_coding

deleterious(0.02)

benign(0.139)

TCGA-AG-A002-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

SVIP

SNV

Missense_Mutation

novel

c.83N>A

p.Ala28Asp

p.A28D

Q8NHG7

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

SVIP

SNV

Missense_Mutation

rs377766261

c.152N>T

p.Arg51Ile

p.R51I

Q8NHG7

protein_coding

deleterious(0.01)

benign(0.374)

TCGA-AP-A056-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

SVIP

SNV

Missense_Mutation

c.164N>G

p.Glu55Gly

p.E55G

Q8NHG7

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-AP-A059-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

SVIP

SNV

Missense_Mutation

rs377766261

c.152G>T

p.Arg51Ile

p.R51I

Q8NHG7

protein_coding

deleterious(0.01)

benign(0.374)

TCGA-B5-A1MR-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Unknown

SVIP

SNV

Missense_Mutation

rs375026736

c.115C>T

p.Arg39Trp

p.R39W

Q8NHG7

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-BG-A2L7-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Chemotherapy

carboplatin

SVIP

SNV

Missense_Mutation

novel

c.41N>A

p.Pro14His

p.P14H

Q8NHG7

protein_coding

tolerated(0.17)

benign(0.242)

TCGA-DD-AAVV-01

Liver

liver hepatocellular carcinoma

Male

<65

I/II

Unknown

SVIP

SNV

Missense_Mutation

novel

c.85N>T

p.Ala29Ser

p.A29S

Q8NHG7

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-85-8276-01

Lung

lung squamous cell carcinoma

Male

<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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