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: ADGRF1

Gene summary for ADGRF1

Gene summary.

Gene information	Species	Human
	Gene symbol	ADGRF1
	Gene ID	266977
	Gene name	adhesion G protein-coupled receptor F1
	Gene Alias	GPR110
	Cytomap	6p12.3
	Gene Type	protein-coding
	GO ID	GO:0003008
	UniProtAcc	Q3SXM8

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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
266977	ADGRF1	CA_HPV_2	Human	Cervix	CC	3.32e-13	3.21e-01	0.0391
266977	ADGRF1	CCI_1	Human	Cervix	CC	1.88e-04	7.80e-01	0.528
266977	ADGRF1	H2	Human	Cervix	HSIL_HPV	3.57e-25	7.09e-01	0.0632
266977	ADGRF1	LZE5T	Human	Esophagus	ESCC	1.28e-07	5.29e-01	0.0514
266977	ADGRF1	LZE8T	Human	Esophagus	ESCC	2.13e-11	3.77e-01	0.067
266977	ADGRF1	LZE20T	Human	Esophagus	ESCC	1.74e-07	2.52e-01	0.0662
266977	ADGRF1	LZE22T	Human	Esophagus	ESCC	1.57e-02	4.31e-01	0.068
266977	ADGRF1	P1T-E	Human	Esophagus	ESCC	3.58e-07	1.13e+00	0.0875
266977	ADGRF1	P8T-E	Human	Esophagus	ESCC	1.61e-32	7.53e-01	0.0889
266977	ADGRF1	P23T-E	Human	Esophagus	ESCC	6.47e-17	1.17e+00	0.108
266977	ADGRF1	P39T-E	Human	Esophagus	ESCC	1.30e-15	4.08e-01	0.0894
266977	ADGRF1	P47T-E	Human	Esophagus	ESCC	1.88e-04	2.59e-01	0.1067
266977	ADGRF1	P54T-E	Human	Esophagus	ESCC	1.64e-05	2.65e-01	0.0975
266977	ADGRF1	P62T-E	Human	Esophagus	ESCC	5.46e-06	4.03e-01	0.1302
266977	ADGRF1	P74T-E	Human	Esophagus	ESCC	1.96e-03	2.19e-01	0.1479
266977	ADGRF1	P75T-E	Human	Esophagus	ESCC	4.12e-11	4.39e-01	0.1125
266977	ADGRF1	P82T-E	Human	Esophagus	ESCC	6.98e-18	1.44e+00	0.1072
266977	ADGRF1	P84T-E	Human	Esophagus	ESCC	2.46e-07	7.12e-01	0.0933
266977	ADGRF1	P104T-E	Human	Esophagus	ESCC	6.28e-04	2.72e-01	0.0931
266977	ADGRF1	P127T-E	Human	Esophagus	ESCC	3.53e-27	8.48e-01	0.0826

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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:00343298	Cervix	CC	cell junction assembly	88/2311	420/18723	3.42e-07	1.38e-05	88
GO:00510904	Cervix	CC	regulation of DNA-binding transcription factor activity	87/2311	440/18723	4.85e-06	1.22e-04	87
GO:00510915	Cervix	CC	positive regulation of DNA-binding transcription factor activity	51/2311	260/18723	5.05e-04	4.92e-03	51
GO:005109012	Cervix	HSIL_HPV	regulation of DNA-binding transcription factor activity	35/737	440/18723	6.77e-05	1.58e-03	35
GO:005109112	Cervix	HSIL_HPV	positive regulation of DNA-binding transcription factor activity	24/737	260/18723	1.01e-04	2.16e-03	24
GO:003432913	Cervix	HSIL_HPV	cell junction assembly	28/737	420/18723	4.82e-03	3.98e-02	28
GO:00510908	Esophagus	ESCC	regulation of DNA-binding transcription factor activity	252/8552	440/18723	5.22e-07	6.97e-06	252
GO:00510918	Esophagus	ESCC	positive regulation of DNA-binding transcription factor activity	155/8552	260/18723	3.83e-06	4.14e-05	155
GO:003432918	Esophagus	ESCC	cell junction assembly	227/8552	420/18723	3.06e-04	1.83e-03	227
GO:00343297	Lung	IAC	cell junction assembly	86/2061	420/18723	7.98e-09	1.10e-06	86
GO:00510903	Lung	IAC	regulation of DNA-binding transcription factor activity	76/2061	440/18723	4.44e-05	1.05e-03	76
GO:00510914	Lung	IAC	positive regulation of DNA-binding transcription factor activity	50/2061	260/18723	5.87e-05	1.29e-03	50
GO:00508085	Lung	IAC	synapse organization	65/2061	426/18723	4.05e-03	3.31e-02	65
GO:003432912	Lung	AIS	cell junction assembly	84/1849	420/18723	2.16e-10	5.71e-08	84
GO:005080811	Lung	AIS	synapse organization	63/1849	426/18723	7.39e-04	1.07e-02	63
GO:005109011	Lung	AIS	regulation of DNA-binding transcription factor activity	64/1849	440/18723	1.04e-03	1.36e-02	64
GO:005109111	Lung	AIS	positive regulation of DNA-binding transcription factor activity	41/1849	260/18723	1.77e-03	2.01e-02	41
GO:00510907	Oral cavity	OSCC	regulation of DNA-binding transcription factor activity	221/7305	440/18723	9.06e-07	1.23e-05	221
GO:00510917	Oral cavity	OSCC	positive regulation of DNA-binding transcription factor activity	134/7305	260/18723	2.52e-05	2.35e-04	134
GO:003432916	Oral cavity	OSCC	cell junction assembly	190/7305	420/18723	4.99e-03	1.96e-02	190

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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

ADGRF1

SNV

Missense_Mutation

c.2435T>G

p.Val812Gly

p.V812G

Q5T601

protein_coding

deleterious(0)

possibly_damaging(0.688)

TCGA-A2-A259-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

ADGRF1

SNV

Missense_Mutation

c.2191N>T

p.Asp731Tyr

p.D731Y

Q5T601

protein_coding

deleterious(0)

possibly_damaging(0.905)

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

ADGRF1

SNV

Missense_Mutation

c.1643N>T

p.Gly548Val

p.G548V

Q5T601

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-BH-A0B5-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

ADGRF1

SNV

Missense_Mutation

c.2684N>A

p.Gly895Glu

p.G895E

Q5T601

protein_coding

deleterious(0.03)

possibly_damaging(0.652)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

ADGRF1

SNV

Missense_Mutation

novel

c.2236N>A

p.Ala746Thr

p.A746T

Q5T601

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-EW-A6SA-01

Breast

breast invasive carcinoma

Male

<65

I/II

Unknown

ADGRF1

insertion

Frame_Shift_Ins

novel

c.2422_2423insACGTTGTCGGAAAAAAGGGGAATTCTTTTTACCTT

p.Ile808AsnfsTer13

p.I808Nfs*13

Q5T601

protein_coding

TCGA-A8-A0A4-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

ADGRF1

SNV

Missense_Mutation

novel

c.2278G>A

p.Val760Ile

p.V760I

Q5T601

protein_coding

tolerated(0.84)

benign(0.001)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ADGRF1

SNV

Missense_Mutation

rs112946460

c.1636G>A

p.Asp546Asn

p.D546N

Q5T601

protein_coding

tolerated(0.74)

benign(0)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ADGRF1

SNV

Missense_Mutation

c.1743N>G

p.Ile581Met

p.I581M

Q5T601

protein_coding

deleterious(0.03)

benign(0.073)

TCGA-HM-A4S6-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

ADGRF1

SNV

Missense_Mutation

c.572G>C

p.Arg191Thr

p.R191T

Q5T601

protein_coding

tolerated(0.65)

benign(0.134)

TCGA-Q1-A73O-01

Cervix

cervical & endocervical cancer

Female

<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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