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: VBP1

Gene summary for VBP1

Gene summary.

Gene information	Species	Human
	Gene symbol	VBP1
	Gene ID	7411
	Gene name	VHL binding protein 1
	Gene Alias	HIBBJ46
	Cytomap	Xq28
	Gene Type	protein-coding
	GO ID	GO:0006457
	UniProtAcc	D3DWY7

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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
7411	VBP1	P91T-E	Human	Esophagus	ESCC	3.02e-23	2.65e+00	0.1828
7411	VBP1	P107T-E	Human	Esophagus	ESCC	2.89e-56	1.45e+00	0.171
7411	VBP1	P126T-E	Human	Esophagus	ESCC	1.37e-11	9.45e-01	0.1125
7411	VBP1	P127T-E	Human	Esophagus	ESCC	5.37e-29	5.71e-01	0.0826
7411	VBP1	P128T-E	Human	Esophagus	ESCC	1.56e-44	1.65e+00	0.1241
7411	VBP1	P130T-E	Human	Esophagus	ESCC	4.01e-73	1.87e+00	0.1676
7411	VBP1	HCC1_Meng	Human	Liver	HCC	5.16e-77	2.11e-01	0.0246
7411	VBP1	HCC2_Meng	Human	Liver	HCC	1.46e-43	2.50e-01	0.0107
7411	VBP1	cirrhotic2	Human	Liver	Cirrhotic	4.28e-06	1.35e-01	0.0201
7411	VBP1	HCC1	Human	Liver	HCC	1.67e-04	3.63e+00	0.5336
7411	VBP1	HCC2	Human	Liver	HCC	1.14e-03	2.92e+00	0.5341
7411	VBP1	HCC5	Human	Liver	HCC	4.24e-06	4.10e-01	0.4932
7411	VBP1	Pt13.b	Human	Liver	HCC	1.46e-14	1.80e-01	0.0251
7411	VBP1	Pt14.b	Human	Liver	HCC	2.30e-04	2.28e-01	0.018
7411	VBP1	S014	Human	Liver	HCC	3.50e-13	7.63e-01	0.2254
7411	VBP1	S015	Human	Liver	HCC	1.71e-14	1.07e+00	0.2375
7411	VBP1	S016	Human	Liver	HCC	4.69e-17	9.79e-01	0.2243
7411	VBP1	S027	Human	Liver	HCC	1.55e-15	1.34e+00	0.2446
7411	VBP1	S028	Human	Liver	HCC	1.22e-25	1.43e+00	0.2503
7411	VBP1	S029	Human	Liver	HCC	7.05e-17	1.64e+00	0.2581

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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
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:000645720	Esophagus	HGIN	protein folding	75/2587	212/18723	1.61e-15	3.86e-13	75
GO:190290327	Esophagus	HGIN	regulation of supramolecular fiber organization	79/2587	383/18723	1.40e-04	2.81e-03	79
GO:199000010	Esophagus	HGIN	amyloid fibril formation	13/2587	34/18723	3.51e-04	5.65e-03	13
GO:19059068	Esophagus	HGIN	regulation of amyloid fibril formation	8/2587	16/18723	6.00e-04	8.41e-03	8
GO:19059078	Esophagus	HGIN	negative regulation of amyloid fibril formation	6/2587	13/18723	4.97e-03	4.18e-02	6
GO:0006457110	Esophagus	ESCC	protein folding	163/8552	212/18723	1.13e-20	1.74e-18	163
GO:1902903111	Esophagus	ESCC	regulation of supramolecular fiber organization	237/8552	383/18723	9.06e-11	2.75e-09	237
GO:190590616	Esophagus	ESCC	regulation of amyloid fibril formation	13/8552	16/18723	4.05e-03	1.62e-02	13
GO:190590716	Esophagus	ESCC	negative regulation of amyloid fibril formation	11/8552	13/18723	4.76e-03	1.85e-02	11
GO:00064577	Liver	Cirrhotic	protein folding	114/4634	212/18723	9.23e-20	2.31e-17	114
GO:190290312	Liver	Cirrhotic	regulation of supramolecular fiber organization	148/4634	383/18723	8.85e-10	4.08e-08	148
GO:19900003	Liver	Cirrhotic	amyloid fibril formation	19/4634	34/18723	1.01e-04	1.05e-03	19
GO:1905907	Liver	Cirrhotic	negative regulation of amyloid fibril formation	10/4634	13/18723	1.14e-04	1.14e-03	10
GO:19029046	Liver	Cirrhotic	negative regulation of supramolecular fiber organization	63/4634	167/18723	1.29e-04	1.26e-03	63
GO:1905906	Liver	Cirrhotic	regulation of amyloid fibril formation	11/4634	16/18723	2.58e-04	2.30e-03	11
GO:000645712	Liver	HCC	protein folding	160/7958	212/18723	1.07e-22	1.88e-20	160
GO:190290322	Liver	HCC	regulation of supramolecular fiber organization	224/7958	383/18723	1.54e-10	5.33e-09	224
GO:199000011	Liver	HCC	amyloid fibril formation	24/7958	34/18723	8.62e-04	5.13e-03	24
GO:190290412	Liver	HCC	negative regulation of supramolecular fiber organization	90/7958	167/18723	1.90e-03	9.69e-03	90
GO:19059071	Liver	HCC	negative regulation of amyloid fibril formation	11/7958	13/18723	2.38e-03	1.16e-02	11

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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

VBP1

SNV

Missense_Mutation

c.85G>A

p.Val29Met

p.V29M

P61758

protein_coding

tolerated(0.17)

possibly_damaging(0.499)

TCGA-B6-A0RL-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

VBP1

insertion

Nonsense_Mutation

novel

c.548_549insGTAAATATATTCTTTAACCAAGGGGTCAGCAAACTTTC

p.Asp183GlufsTer2

p.D183Efs*2

P61758

protein_coding

TCGA-A8-A07J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

VBP1

SNV

Missense_Mutation

novel

c.315N>A

p.Phe105Leu

p.F105L

P61758

protein_coding

deleterious(0)

probably_damaging(0.936)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

VBP1

SNV

Missense_Mutation

c.120N>T

p.Gln40His

p.Q40H

P61758

protein_coding

deleterious(0.02)

possibly_damaging(0.556)

TCGA-CK-4951-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

VBP1

SNV

Missense_Mutation

novel

c.207A>C

p.Gln69His

p.Q69H

P61758

protein_coding

deleterious(0.02)

possibly_damaging(0.905)

TCGA-A5-A0G1-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

VBP1

SNV

Missense_Mutation

c.164N>G

p.Glu55Gly

p.E55G

P61758

protein_coding

deleterious(0.01)

probably_damaging(0.996)

TCGA-AP-A0LM-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

VBP1

SNV

Missense_Mutation

c.438N>T

p.Lys146Asn

p.K146N

P61758

protein_coding

tolerated(0.1)

benign(0.146)

TCGA-AP-A0LM-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

VBP1

SNV

Missense_Mutation

novel

c.446C>T

p.Ser149Leu

p.S149L

P61758

protein_coding

tolerated(0.05)

benign(0.003)

TCGA-AP-A1DK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

VBP1

SNV

Missense_Mutation

novel

c.311N>T

p.Arg104Ile

p.R104I

P61758

protein_coding

deleterious(0.02)

possibly_damaging(0.767)

TCGA-AX-A06F-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatin

VBP1

SNV

Missense_Mutation

c.197N>G

p.Asn66Ser

p.N66S

P61758

protein_coding

tolerated(0.1)

benign(0.106)

TCGA-B5-A11E-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

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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