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: GIGYF2

Gene summary for GIGYF2

Gene summary.

Gene information	Species	Human
	Gene symbol	GIGYF2
	Gene ID	26058
	Gene name	GRB10 interacting GYF protein 2
	Gene Alias	GYF2
	Cytomap	2q37.1
	Gene Type	protein-coding
	GO ID	GO:0000075
	UniProtAcc	Q6Y7W6

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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
26058	GIGYF2	RNA-P7T1-P7T1-3	Human	Lung	AIS	1.90e-02	4.65e-01	-0.0822
26058	GIGYF2	RNA-P7T1-P7T1-4	Human	Lung	AIS	1.16e-06	6.03e-01	-0.0809
26058	GIGYF2	C21	Human	Oral cavity	OSCC	4.27e-22	8.48e-01	0.2678
26058	GIGYF2	C30	Human	Oral cavity	OSCC	9.28e-08	5.60e-01	0.3055
26058	GIGYF2	C43	Human	Oral cavity	OSCC	1.21e-07	1.59e-01	0.1704
26058	GIGYF2	C46	Human	Oral cavity	OSCC	2.05e-06	2.21e-01	0.1673
26058	GIGYF2	C51	Human	Oral cavity	OSCC	7.80e-03	4.21e-01	0.2674
26058	GIGYF2	C57	Human	Oral cavity	OSCC	1.98e-02	2.86e-01	0.1679
26058	GIGYF2	C08	Human	Oral cavity	OSCC	1.24e-16	3.39e-01	0.1919
26058	GIGYF2	EOLP-1	Human	Oral cavity	EOLP	6.56e-09	2.87e-01	-0.0202
26058	GIGYF2	NEOLP-1	Human	Oral cavity	NEOLP	6.93e-06	2.67e-01	-0.0194
26058	GIGYF2	NEOLP-2	Human	Oral cavity	NEOLP	1.41e-04	1.98e-01	-0.0196
26058	GIGYF2	NEOLP-3	Human	Oral cavity	NEOLP	5.45e-03	1.70e-01	-0.0191
26058	GIGYF2	SYSMH1	Human	Oral cavity	OSCC	1.76e-05	2.08e-01	0.1127
26058	GIGYF2	SYSMH2	Human	Oral cavity	OSCC	2.98e-10	2.34e-01	0.2326
26058	GIGYF2	SYSMH3	Human	Oral cavity	OSCC	3.80e-19	5.67e-01	0.2442
26058	GIGYF2	SYSMH5	Human	Oral cavity	OSCC	5.46e-07	2.22e-01	0.0647
26058	GIGYF2	SYSMH6	Human	Oral cavity	OSCC	1.85e-06	1.92e-01	0.1275
26058	GIGYF2	HTA12-15-2	Human	Pancreas	PDAC	3.74e-04	3.82e-01	0.2315
26058	GIGYF2	HTA12-23-1	Human	Pancreas	PDAC	1.89e-03	6.02e-01	0.3405

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
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
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
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:0009896	Colorectum	AD	positive regulation of catabolic process	180/3918	492/18723	4.33e-16	1.94e-13	180
GO:1903311	Colorectum	AD	regulation of mRNA metabolic process	117/3918	288/18723	1.69e-14	4.23e-12	117
GO:0031331	Colorectum	AD	positive regulation of cellular catabolic process	156/3918	427/18723	4.68e-14	1.05e-11	156
GO:0006401	Colorectum	AD	RNA catabolic process	102/3918	278/18723	8.64e-10	6.76e-08	102
GO:0044270	Colorectum	AD	cellular nitrogen compound catabolic process	147/3918	451/18723	3.35e-09	2.23e-07	147
GO:0046700	Colorectum	AD	heterocycle catabolic process	145/3918	445/18723	4.37e-09	2.84e-07	145
GO:0006402	Colorectum	AD	mRNA catabolic process	87/3918	232/18723	4.40e-09	2.84e-07	87
GO:0034655	Colorectum	AD	nucleobase-containing compound catabolic process	133/3918	407/18723	1.56e-08	9.12e-07	133
GO:0019439	Colorectum	AD	aromatic compound catabolic process	146/3918	467/18723	7.48e-08	3.84e-06	146
GO:1901361	Colorectum	AD	organic cyclic compound catabolic process	153/3918	495/18723	8.23e-08	4.18e-06	153
GO:0061013	Colorectum	AD	regulation of mRNA catabolic process	64/3918	166/18723	1.44e-07	6.59e-06	64
GO:0043487	Colorectum	AD	regulation of RNA stability	63/3918	170/18723	9.17e-07	3.12e-05	63
GO:0006417	Colorectum	AD	regulation of translation	141/3918	468/18723	1.32e-06	4.22e-05	141
GO:0043488	Colorectum	AD	regulation of mRNA stability	59/3918	158/18723	1.50e-06	4.66e-05	59
GO:0048872	Colorectum	AD	homeostasis of number of cells	87/3918	272/18723	1.16e-05	2.61e-04	87
GO:1903313	Colorectum	AD	positive regulation of mRNA metabolic process	44/3918	118/18723	3.20e-05	5.87e-04	44
GO:0060249	Colorectum	AD	anatomical structure homeostasis	94/3918	314/18723	9.37e-05	1.42e-03	94
GO:0001894	Colorectum	AD	tissue homeostasis	81/3918	268/18723	1.96e-04	2.62e-03	81
GO:0061014	Colorectum	AD	positive regulation of mRNA catabolic process	32/3918	87/18723	4.81e-04	5.27e-03	32
GO:0009791	Colorectum	AD	post-embryonic development	29/3918	80/18723	1.13e-03	1.03e-02	29

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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

GIGYF2

SNV

Missense_Mutation

novel

c.2206N>T

p.Asp736Tyr

p.D736Y

Q6Y7W6

protein_coding

deleterious(0.01)

probably_damaging(0.999)

TCGA-A7-A4SF-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

GIGYF2

SNV

Missense_Mutation

c.1021N>A

p.Glu341Lys

p.E341K

Q6Y7W6

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-D8-A1J8-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

nolvadex

GIGYF2

SNV

Missense_Mutation

rs372418931

c.3059N>T

p.Thr1020Met

p.T1020M

Q6Y7W6

protein_coding

tolerated(0.46)

benign(0.441)

TCGA-E2-A15C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

GIGYF2

insertion

Nonsense_Mutation

novel

c.3493_3494insTCTCCTGGGCTGGAATGTAGCTAGGACT

p.His1165LeufsTer7

p.H1165Lfs*7

Q6Y7W6

protein_coding

TCGA-A8-A07J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

GIGYF2

deletion

Frame_Shift_Del

c.734delN

p.Ala245ValfsTer56

p.A245Vfs*56

Q6Y7W6

protein_coding

TCGA-D8-A1JK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

GIGYF2

SNV

Missense_Mutation

c.3323N>A

p.Gly1108Glu

p.G1108E

Q6Y7W6

protein_coding

deleterious(0)

benign(0.015)

TCGA-C5-A1MH-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

GIGYF2

SNV

Missense_Mutation

c.712N>A

p.Glu238Lys

p.E238K

Q6Y7W6

protein_coding

tolerated(0.1)

possibly_damaging(0.776)

TCGA-DR-A0ZM-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unspecific

Cisplatin

GIGYF2

SNV

Missense_Mutation

rs754519471

c.2402N>A

p.Arg801Gln

p.R801Q

Q6Y7W6

protein_coding

tolerated(0.26)

benign(0.297)

TCGA-EA-A3HS-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

GIGYF2

SNV

Missense_Mutation

novel

c.937N>A

p.Glu313Lys

p.E313K

Q6Y7W6

protein_coding

deleterious(0.01)

possibly_damaging(0.857)

TCGA-ZJ-AB0H-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

GIGYF2

SNV

Missense_Mutation

c.2423N>A

p.Arg808Gln

p.R808Q

Q6Y7W6

protein_coding

deleterious(0.01)

probably_damaging(0.953)

TCGA-AA-3672-01

Colorectum

colon adenocarcinoma

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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