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: HGF

Gene summary for HGF

Gene summary.

Gene information	Species	Human
	Gene symbol	HGF
	Gene ID	3082
	Gene name	hepatocyte growth factor
	Gene Alias	DFNB39
	Cytomap	7q21.11
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	P14210

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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
3082	HGF	ATC12	Human	Thyroid	ATC	1.06e-50	1.26e+00	0.34
3082	HGF	ATC13	Human	Thyroid	ATC	2.48e-11	2.29e-01	0.34
3082	HGF	ATC4	Human	Thyroid	ATC	5.56e-59	1.47e+00	0.34
3082	HGF	ATC5	Human	Thyroid	ATC	2.61e-10	2.60e-01	0.34

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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:200123335	Thyroid	ATC	regulation of apoptotic signaling pathway	206/6293	356/18723	2.81e-21	5.92e-19	206
GO:000697934	Thyroid	ATC	response to oxidative stress	246/6293	446/18723	2.98e-21	6.09e-19	246
GO:001050632	Thyroid	ATC	regulation of autophagy	180/6293	317/18723	1.34e-17	1.46e-15	180
GO:001056334	Thyroid	ATC	negative regulation of phosphorus metabolic process	234/6293	442/18723	2.30e-17	2.31e-15	234
GO:006219734	Thyroid	ATC	cellular response to chemical stress	188/6293	337/18723	3.16e-17	3.07e-15	188
GO:004593634	Thyroid	ATC	negative regulation of phosphate metabolic process	233/6293	441/18723	3.68e-17	3.47e-15	233
GO:000193333	Thyroid	ATC	negative regulation of protein phosphorylation	186/6293	342/18723	1.43e-15	1.08e-13	186
GO:004232634	Thyroid	ATC	negative regulation of phosphorylation	203/6293	385/18723	5.30e-15	3.53e-13	203
GO:003459934	Thyroid	ATC	cellular response to oxidative stress	158/6293	288/18723	7.35e-14	3.94e-12	158
GO:003134623	Thyroid	ATC	positive regulation of cell projection organization	186/6293	353/18723	7.99e-14	4.23e-12	186
GO:2001234210	Thyroid	ATC	negative regulation of apoptotic signaling pathway	129/6293	224/18723	1.26e-13	6.46e-12	129
GO:000030234	Thyroid	ATC	response to reactive oxygen species	128/6293	222/18723	1.38e-13	7.00e-12	128
GO:004254233	Thyroid	ATC	response to hydrogen peroxide	92/6293	146/18723	3.12e-13	1.46e-11	92
GO:0097191210	Thyroid	ATC	extrinsic apoptotic signaling pathway	125/6293	219/18723	7.19e-13	3.16e-11	125
GO:000150332	Thyroid	ATC	ossification	206/6293	408/18723	9.23e-13	3.95e-11	206
GO:001063926	Thyroid	ATC	negative regulation of organelle organization	179/6293	348/18723	3.74e-12	1.50e-10	179
GO:005105219	Thyroid	ATC	regulation of DNA metabolic process	183/6293	359/18723	5.97e-12	2.30e-10	183
GO:2001236210	Thyroid	ATC	regulation of extrinsic apoptotic signaling pathway	89/6293	151/18723	1.43e-10	4.40e-09	89
GO:004873233	Thyroid	ATC	gland development	210/6293	436/18723	1.50e-10	4.59e-09	210
GO:001097523	Thyroid	ATC	regulation of neuron projection development	212/6293	445/18723	4.16e-10	1.14e-08	212

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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
HGF	MET	HGF_MET	HGF	Breast	Healthy
HGF	MET	HGF_MET	HGF	Cervix	Precancer
HGF	MET	HGF_MET	HGF	Endometrium	EEC
HGF	MET	HGF_MET	HGF	Liver	HCC
HGF	MET	HGF_MET	HGF	Liver	Healthy
HGF	MET	HGF_MET	HGF	Liver	Precancer
HGF	MET	HGF_MET	HGF	Lung	IAC
HGF	MET	HGF_MET	HGF	Prostate	BPH
HGF	MET	HGF_MET	HGF	Prostate	Healthy
HGF	MET	HGF_MET	HGF	THCA	Cancer

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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

HGF

SNV

Missense_Mutation

novel

c.1535G>T

p.Arg512Ile

p.R512I

P14210

protein_coding

deleterious(0.02)

benign(0.054)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HGF

SNV

Missense_Mutation

c.1748N>C

p.Lys583Thr

p.K583T

P14210

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HGF

SNV

Missense_Mutation

c.377N>C

p.Arg126Thr

p.R126T

P14210

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-AR-A0TZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unspecific

Doxorubicin

HGF

SNV

Missense_Mutation

c.248C>G

p.Thr83Ser

p.T83S

P14210

protein_coding

tolerated(0.35)

benign(0.006)

TCGA-BH-A0BF-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

HGF

SNV

Missense_Mutation

c.1913N>A

p.Gly638Glu

p.G638E

P14210

protein_coding

deleterious(0.03)

probably_damaging(0.979)

TCGA-C8-A26W-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

HGF

SNV

Missense_Mutation

rs778704152

c.1675N>A

p.Glu559Lys

p.E559K

P14210

protein_coding

tolerated(0.44)

probably_damaging(0.992)

TCGA-GM-A2D9-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

HGF

SNV

Missense_Mutation

rs777593933

c.589C>T

p.Arg197Cys

p.R197C

P14210

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

HGF

SNV

Missense_Mutation

c.686N>C

p.Gly229Ala

p.G229A

P14210

protein_coding

deleterious(0)

possibly_damaging(0.672)

TCGA-C5-A1BQ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

HGF

SNV

Missense_Mutation

c.343N>C

p.Glu115Gln

p.E115Q

P14210

protein_coding

tolerated(0.28)

benign(0.352)

TCGA-C5-A1BQ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

HGF

SNV

Missense_Mutation

c.331G>A

p.Glu111Lys

p.E111K

P14210

protein_coding

tolerated(0.86)

benign(0)

TCGA-C5-A1MH-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

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
3082	HGF	PROTEASE, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, GROWTH FACTOR, KINASE, ENZYME		STI571	IMATINIB MESYLATE	11439348
3082	HGF	PROTEASE, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, GROWTH FACTOR, KINASE, ENZYME		THALIDOMIDE	THALIDOMIDE	15939924
3082	HGF	PROTEASE, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, GROWTH FACTOR, KINASE, ENZYME		ASPIRIN	ASPIRIN	11981761
3082	HGF	PROTEASE, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, GROWTH FACTOR, KINASE, ENZYME		VM-202
3082	HGF	PROTEASE, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, GROWTH FACTOR, KINASE, ENZYME		Ficlatuzumab	FICLATUZUMAB
3082	HGF	PROTEASE, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, GROWTH FACTOR, KINASE, ENZYME		PROTEOLYTIC ENZYMES		9502079
3082	HGF	PROTEASE, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, GROWTH FACTOR, KINASE, ENZYME	antibody	RILOTUMUMAB	RILOTUMUMAB
3082	HGF	PROTEASE, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, GROWTH FACTOR, KINASE, ENZYME		RESVERATROL	RESVERATROL	15672869
3082	HGF	PROTEASE, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, GROWTH FACTOR, KINASE, ENZYME		TAK-701
3082	HGF	PROTEASE, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, GROWTH FACTOR, KINASE, ENZYME		FICLATUZUMAB	FICLATUZUMAB

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