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:003243513	Prostate	Tumor	negative regulation of proteasomal ubiquitin-dependent protein catabolic process	18/3246	35/18723	4.26e-06	6.72e-05	18
GO:001050614	Prostate	Tumor	regulation of autophagy	86/3246	317/18723	7.77e-06	1.16e-04	86
GO:003133317	Prostate	Tumor	negative regulation of protein-containing complex assembly	45/3246	141/18723	1.69e-05	2.25e-04	45
GO:190179912	Prostate	Tumor	negative regulation of proteasomal protein catabolic process	21/3246	49/18723	2.59e-05	3.18e-04	21
GO:003043312	Prostate	Tumor	ubiquitin-dependent ERAD pathway	30/3246	85/18723	5.26e-05	5.75e-04	30
GO:005105112	Prostate	Tumor	negative regulation of transport	114/3246	470/18723	7.43e-05	7.82e-04	114
GO:003650313	Prostate	Tumor	ERAD pathway	35/3246	107/18723	8.02e-05	8.19e-04	35
GO:001050814	Prostate	Tumor	positive regulation of autophagy	39/3246	124/18723	8.56e-05	8.53e-04	39
GO:003097012	Prostate	Tumor	retrograde protein transport, ER to cytosol	14/3246	29/18723	1.22e-04	1.14e-03	14
GO:190351312	Prostate	Tumor	endoplasmic reticulum to cytosol transport	14/3246	29/18723	1.22e-04	1.14e-03	14
GO:003252712	Prostate	Tumor	protein exit from endoplasmic reticulum	19/3246	48/18723	2.23e-04	1.90e-03	19
GO:190382812	Prostate	Tumor	negative regulation of cellular protein localization	36/3246	117/18723	2.55e-04	2.14e-03	36
GO:007086111	Prostate	Tumor	regulation of protein exit from endoplasmic reticulum	12/3246	27/18723	9.52e-04	6.20e-03	12
GO:00708622	Prostate	Tumor	negative regulation of protein exit from endoplasmic reticulum	6/3246	10/18723	3.00e-03	1.61e-02	6
GO:003238711	Prostate	Tumor	negative regulation of intracellular transport	19/3246	58/18723	3.18e-03	1.66e-02	19
GO:190495011	Prostate	Tumor	negative regulation of establishment of protein localization	35/3246	131/18723	4.63e-03	2.28e-02	35
GO:005122411	Prostate	Tumor	negative regulation of protein transport	34/3246	127/18723	5.03e-03	2.45e-02	34
GO:19041522	Prostate	Tumor	regulation of retrograde protein transport, ER to cytosol	7/3246	14/18723	5.15e-03	2.48e-02	7
GO:00903172	Prostate	Tumor	negative regulation of intracellular protein transport	14/3246	42/18723	8.95e-03	3.87e-02	14
GO:0010498113	Thyroid	PTC	proteasomal protein catabolic process	297/5968	490/18723	4.58e-40	9.63e-37	297

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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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