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: GGNBP2

Gene summary for GGNBP2

Gene summary.

Gene information	Species	Human
	Gene symbol	GGNBP2
	Gene ID	79893
	Gene name	gametogenetin binding protein 2
	Gene Alias	DIF-3
	Cytomap	17q12
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	Q9H3C7

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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
79893	GGNBP2	HTA11_3410_2000001011	Human	Colorectum	AD	1.21e-09	-5.63e-01	0.0155
79893	GGNBP2	HTA11_347_2000001011	Human	Colorectum	AD	1.07e-05	3.78e-01	-0.1954
79893	GGNBP2	HTA11_866_3004761011	Human	Colorectum	AD	1.93e-06	-5.34e-01	0.096
79893	GGNBP2	HTA11_10711_2000001011	Human	Colorectum	AD	3.31e-02	-4.46e-01	0.0338
79893	GGNBP2	HTA11_7696_3000711011	Human	Colorectum	AD	7.69e-03	-2.65e-01	0.0674
79893	GGNBP2	HTA11_99999970781_79442	Human	Colorectum	MSS	1.42e-03	-2.80e-01	0.294
79893	GGNBP2	HTA11_99999971662_82457	Human	Colorectum	MSS	1.00e-02	-3.18e-01	0.3859
79893	GGNBP2	HTA11_99999974143_84620	Human	Colorectum	MSS	3.08e-07	-4.13e-01	0.3005
79893	GGNBP2	A002-C-010	Human	Colorectum	FAP	2.91e-07	-3.14e-01	0.242
79893	GGNBP2	A001-C-207	Human	Colorectum	FAP	2.27e-02	-2.41e-01	0.1278
79893	GGNBP2	A015-C-203	Human	Colorectum	FAP	9.77e-29	-1.94e-01	-0.1294
79893	GGNBP2	A015-C-204	Human	Colorectum	FAP	4.08e-05	2.71e-02	-0.0228
79893	GGNBP2	A014-C-040	Human	Colorectum	FAP	3.04e-03	-7.85e-02	-0.1184
79893	GGNBP2	A002-C-201	Human	Colorectum	FAP	5.50e-10	-2.23e-01	0.0324
79893	GGNBP2	A002-C-203	Human	Colorectum	FAP	2.86e-05	-2.31e-01	0.2786
79893	GGNBP2	A001-C-119	Human	Colorectum	FAP	3.47e-13	4.14e-01	-0.1557
79893	GGNBP2	A001-C-108	Human	Colorectum	FAP	5.72e-17	-9.81e-02	-0.0272
79893	GGNBP2	A002-C-205	Human	Colorectum	FAP	2.92e-23	1.57e-01	-0.1236
79893	GGNBP2	A001-C-104	Human	Colorectum	FAP	1.31e-06	-5.90e-02	0.0184
79893	GGNBP2	A015-C-005	Human	Colorectum	FAP	3.80e-03	-1.94e-01	-0.0336

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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
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:001056328	Skin	cSCC	negative regulation of phosphorus metabolic process	160/4864	442/18723	1.04e-06	1.85e-05	160
GO:004232626	Skin	cSCC	negative regulation of phosphorylation	137/4864	385/18723	1.63e-05	1.99e-04	137
GO:000189223	Skin	cSCC	embryonic placenta development	39/4864	82/18723	2.08e-05	2.43e-04	39
GO:006145825	Skin	cSCC	reproductive system development	149/4864	427/18723	2.30e-05	2.65e-04	149
GO:004860824	Skin	cSCC	reproductive structure development	148/4864	424/18723	2.40e-05	2.74e-04	148
GO:000193326	Skin	cSCC	negative regulation of protein phosphorylation	123/4864	342/18723	2.48e-05	2.82e-04	123
GO:005134829	Skin	cSCC	negative regulation of transferase activity	100/4864	268/18723	2.60e-05	2.94e-04	100
GO:000189024	Skin	cSCC	placenta development	60/4864	144/18723	2.84e-05	3.17e-04	60
GO:006071122	Skin	cSCC	labyrinthine layer development	23/4864	44/18723	1.74e-04	1.49e-03	23
GO:00610998	Skin	cSCC	negative regulation of protein tyrosine kinase activity	17/4864	31/18723	5.90e-04	4.27e-03	17
GO:0006469110	Skin	cSCC	negative regulation of protein kinase activity	74/4864	212/18723	2.36e-03	1.37e-02	74
GO:006109721	Skin	cSCC	regulation of protein tyrosine kinase activity	36/4864	90/18723	2.48e-03	1.42e-02	36
GO:0033673110	Skin	cSCC	negative regulation of kinase activity	81/4864	237/18723	2.95e-03	1.64e-02	81
GO:00507323	Skin	cSCC	negative regulation of peptidyl-tyrosine phosphorylation	25/4864	59/18723	4.46e-03	2.29e-02	25
GO:001820923	Skin	cSCC	peptidyl-serine modification	108/4864	338/18723	7.73e-03	3.60e-02	108
GO:0010563113	Thyroid	PTC	negative regulation of phosphorus metabolic process	219/5968	442/18723	4.47e-15	3.07e-13	219
GO:0045936113	Thyroid	PTC	negative regulation of phosphate metabolic process	218/5968	441/18723	7.08e-15	4.75e-13	218
GO:0001933113	Thyroid	PTC	negative regulation of protein phosphorylation	173/5968	342/18723	3.46e-13	1.75e-11	173
GO:0042326113	Thyroid	PTC	negative regulation of phosphorylation	189/5968	385/18723	1.00e-12	4.64e-11	189
GO:0051348113	Thyroid	PTC	negative regulation of transferase activity	137/5968	268/18723	3.78e-11	1.36e-09	137

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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

GGNBP2

SNV

Missense_Mutation

novel

c.308N>C

p.Leu103Pro

p.L103P

Q9H3C7

protein_coding

deleterious(0)

probably_damaging(0.952)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

GGNBP2

insertion

Frame_Shift_Ins

novel

c.1108_1109insCGCTAAGTTGCTTTAGTAAGTCTCACAGG

p.Gln370ProfsTer42

p.Q370Pfs*42

Q9H3C7

protein_coding

TCGA-A2-A0YH-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

GGNBP2

insertion

Nonsense_Mutation

novel

c.824_825insGCGTATGTTTTAAATGTGTGTATGGAGGCTTATTTTGGATGCTGTAGA

p.Ala275_Glu276insArgMetPheTerMetCysValTrpArgLeuIleLeuAspAlaValAsp

p.A275_E276insRMF*MCVWRLILDAVD

Q9H3C7

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

GGNBP2

SNV

Missense_Mutation

novel

c.2077N>G

p.Thr693Ala

p.T693A

Q9H3C7

protein_coding

tolerated_low_confidence(0.13)

benign(0.026)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

GGNBP2

SNV

Missense_Mutation

novel

c.259N>A

p.Val87Ile

p.V87I

Q9H3C7

protein_coding

tolerated(0.19)

benign(0.003)

TCGA-DG-A2KJ-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

GGNBP2

SNV

Missense_Mutation

novel

c.778N>T

p.His260Tyr

p.H260Y

Q9H3C7

protein_coding

deleterious(0)

probably_damaging(0.988)

TCGA-IR-A3LA-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

GGNBP2

SNV

Missense_Mutation

novel

c.583G>C

p.Val195Leu

p.V195L

Q9H3C7

protein_coding

tolerated(0.08)

benign(0.342)

TCGA-IR-A3LK-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

GGNBP2

SNV

Missense_Mutation

novel

c.939C>G

p.Ile313Met

p.I313M

Q9H3C7

protein_coding

deleterious(0)

probably_damaging(0.931)

TCGA-Q1-A6DT-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

GGNBP2

SNV

Missense_Mutation

novel

c.935N>A

p.Arg312Gln

p.R312Q

Q9H3C7

protein_coding

deleterious(0)

probably_damaging(0.984)

TCGA-AA-A00N-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

GGNBP2

SNV

Missense_Mutation

novel

c.1134N>T

p.Lys378Asn

p.K378N

Q9H3C7

protein_coding

tolerated(0.06)

probably_damaging(0.996)

TCGA-AA-A00N-01

Colorectum

colon adenocarcinoma

Male

>=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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