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: VGF

Gene summary for VGF

Gene summary.

Gene information	Species	Human
	Gene symbol	VGF
	Gene ID	7425
	Gene name	VGF nerve growth factor inducible
	Gene Alias	SCG7
	Cytomap	7q22.1
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	O15240

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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
7425	VGF	S015	Human	Liver	HCC	1.31e-05	6.56e-01	0.2375
7425	VGF	S016	Human	Liver	HCC	2.40e-09	7.83e-01	0.2243
7425	VGF	S027	Human	Liver	HCC	2.57e-02	2.13e-01	0.2446
7425	VGF	S028	Human	Liver	HCC	5.42e-05	1.78e-01	0.2503
7425	VGF	ATC09	Human	Thyroid	ATC	2.78e-14	9.84e-01	0.2871
7425	VGF	ATC1	Human	Thyroid	ATC	2.05e-14	1.04e+00	0.2878

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
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:000609122	Liver	HCC	generation of precursor metabolites and energy	340/7958	490/18723	4.04e-34	2.85e-31	340
GO:003286821	Liver	HCC	response to insulin	172/7958	264/18723	7.14e-14	4.23e-12	172
GO:004343422	Liver	HCC	response to peptide hormone	247/7958	414/18723	9.55e-13	4.77e-11	247
GO:003166722	Liver	HCC	response to nutrient levels	276/7958	474/18723	2.30e-12	1.08e-10	276
GO:000926611	Liver	HCC	response to temperature stimulus	101/7958	178/18723	8.55e-05	7.48e-04	101
GO:005159121	Liver	HCC	response to cAMP	57/7958	93/18723	1.96e-04	1.52e-03	57
GO:001407421	Liver	HCC	response to purine-containing compound	84/7958	148/18723	3.19e-04	2.26e-03	84
GO:004259322	Liver	HCC	glucose homeostasis	137/7958	258/18723	3.59e-04	2.49e-03	137
GO:003350022	Liver	HCC	carbohydrate homeostasis	137/7958	259/18723	4.45e-04	2.98e-03	137
GO:004668321	Liver	HCC	response to organophosphorus	73/7958	131/18723	1.52e-03	8.05e-03	73
GO:003559212	Liver	HCC	establishment of protein localization to extracellular region	176/7958	360/18723	7.96e-03	3.15e-02	176
GO:000930612	Liver	HCC	protein secretion	175/7958	359/18723	9.32e-03	3.57e-02	175
GO:006145811	Liver	HCC	reproductive system development	205/7958	427/18723	1.16e-02	4.27e-02	205
GO:000609134	Thyroid	ATC	generation of precursor metabolites and energy	256/6293	490/18723	6.55e-18	7.69e-16	256
GO:004343428	Thyroid	ATC	response to peptide hormone	192/6293	414/18723	3.63e-08	6.70e-07	192
GO:0031667210	Thyroid	ATC	response to nutrient levels	212/6293	474/18723	2.37e-07	3.70e-06	212
GO:006145827	Thyroid	ATC	reproductive system development	193/6293	427/18723	3.32e-07	4.92e-06	193
GO:004860825	Thyroid	ATC	reproductive structure development	190/6293	424/18723	8.40e-07	1.11e-05	190
GO:003286824	Thyroid	ATC	response to insulin	126/6293	264/18723	1.24e-06	1.59e-05	126
GO:000926632	Thyroid	ATC	response to temperature stimulus	83/6293	178/18723	2.03e-04	1.35e-03	83

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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

VGF

SNV

Missense_Mutation

novel

c.594G>T

p.Glu198Asp

p.E198D

O15240

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.806)

TCGA-C8-A8HP-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

5-fluorouracil

VGF

SNV

Missense_Mutation

c.1712N>T

p.Pro571Leu

p.P571L

O15240

protein_coding

tolerated_low_confidence(0.05)

benign(0.33)

TCGA-E9-A1NA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

VGF

SNV

Missense_Mutation

c.1812G>C

p.Glu604Asp

p.E604D

O15240

protein_coding

deleterious_low_confidence(0.02)

benign(0.025)

TCGA-DR-A0ZM-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unspecific

Cisplatin

VGF

SNV

Missense_Mutation

novel

c.28N>A

p.Ala10Thr

p.A10T

O15240

protein_coding

tolerated_low_confidence(0.27)

benign(0)

TCGA-AZ-4315-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

VGF

SNV

Missense_Mutation

rs532601632

c.1136N>T

p.Gly379Val

p.G379V

O15240

protein_coding

tolerated_low_confidence(0.1)

benign(0.095)

TCGA-CK-4951-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

VGF

SNV

Missense_Mutation

novel

c.1337N>G

p.Glu446Gly

p.E446G

O15240

protein_coding

deleterious_low_confidence(0.01)

benign(0.162)

TCGA-CK-6746-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

VGF

SNV

Missense_Mutation

c.1329C>G

p.Asp443Glu

p.D443E

O15240

protein_coding

deleterious_low_confidence(0.02)

possibly_damaging(0.464)

TCGA-G4-6588-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

VGF

SNV

Missense_Mutation

rs761504889

c.1723C>T

p.His575Tyr

p.H575Y

O15240

protein_coding

tolerated_low_confidence(0.31)

benign(0)

TCGA-EI-6881-01

Colorectum

rectum adenocarcinoma

Male

<65

III/IV

Chemotherapy

VGF

SNV

Missense_Mutation

c.801N>T

p.Lys267Asn

p.K267N

O15240

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.898)

TCGA-AP-A059-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

VGF

SNV

Missense_Mutation

novel

c.502N>T

p.Asp168Tyr

p.D168Y

O15240

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.66)

TCGA-B5-A1MR-01

Endometrium

uterine corpus endometrioid carcinoma

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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