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: GGN

Gene summary for GGN

Gene summary.

Gene information	Species	Human
	Gene symbol	GGN
	Gene ID	199720
	Gene name	gametogenetin
	Gene Alias	GGN
	Cytomap	19q13.2
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	Q86UU5

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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
199720	GGN	P38T-E	Human	Esophagus	ESCC	2.16e-21	8.08e-01	0.127
199720	GGN	P56T-E	Human	Esophagus	ESCC	2.55e-18	1.87e+00	0.1613
199720	GGN	P104T-E	Human	Esophagus	ESCC	3.26e-14	6.90e-01	0.0931
199720	GGN	P127T-E	Human	Esophagus	ESCC	2.63e-58	8.69e-01	0.0826

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias

∗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:00610993	Colorectum	CRC	negative regulation of protein tyrosine kinase activity	10/2078	31/18723	1.37e-03	1.50e-02	10
GO:00019335	Colorectum	CRC	negative regulation of protein phosphorylation	55/2078	342/18723	3.05e-03	2.72e-02	55
GO:00459365	Colorectum	CRC	negative regulation of phosphate metabolic process	68/2078	441/18723	3.15e-03	2.78e-02	68
GO:00105635	Colorectum	CRC	negative regulation of phosphorus metabolic process	68/2078	442/18723	3.33e-03	2.85e-02	68
GO:00336734	Colorectum	CRC	negative regulation of kinase activity	40/2078	237/18723	4.58e-03	3.57e-02	40
GO:00485683	Colorectum	CRC	embryonic organ development	65/2078	427/18723	5.15e-03	3.94e-02	65
GO:00017014	Colorectum	CRC	in utero embryonic development	57/2078	367/18723	5.54e-03	4.19e-02	57
GO:00423265	Colorectum	CRC	negative regulation of phosphorylation	59/2078	385/18723	6.45e-03	4.67e-02	59
GO:000170118	Esophagus	HGIN	in utero embryonic development	77/2587	367/18723	9.56e-05	2.05e-03	77
GO:004593626	Esophagus	HGIN	negative regulation of phosphate metabolic process	89/2587	441/18723	1.24e-04	2.54e-03	89
GO:001056326	Esophagus	HGIN	negative regulation of phosphorus metabolic process	89/2587	442/18723	1.34e-04	2.71e-03	89
GO:004232620	Esophagus	HGIN	negative regulation of phosphorylation	78/2587	385/18723	2.77e-04	4.77e-03	78
GO:000189019	Esophagus	HGIN	placenta development	35/2587	144/18723	5.02e-04	7.31e-03	35
GO:000189218	Esophagus	HGIN	embryonic placenta development	23/2587	82/18723	5.47e-04	7.73e-03	23
GO:000193320	Esophagus	HGIN	negative regulation of protein phosphorylation	69/2587	342/18723	6.81e-04	9.26e-03	69
GO:005134827	Esophagus	HGIN	negative regulation of transferase activity	55/2587	268/18723	1.51e-03	1.74e-02	55
GO:006145819	Esophagus	HGIN	reproductive system development	78/2587	427/18723	5.53e-03	4.52e-02	78
GO:000170119	Esophagus	ESCC	in utero embryonic development	243/8552	367/18723	1.00e-15	6.86e-14	243
GO:0010563111	Esophagus	ESCC	negative regulation of phosphorus metabolic process	274/8552	442/18723	2.32e-12	9.41e-11	274
GO:0045936111	Esophagus	ESCC	negative regulation of phosphate metabolic process	273/8552	441/18723	3.18e-12	1.25e-10	273

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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

GGN

SNV

Missense_Mutation

novel

c.1270N>T

p.Gly424Cys

p.G424C

Q86UU5

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.835)

TCGA-AC-A62X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

GGN

SNV

Missense_Mutation

novel

c.13C>A

p.Gln5Lys

p.Q5K

Q86UU5

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.953)

TCGA-E2-A2P6-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

GGN

SNV

Missense_Mutation

novel

c.1646N>A

p.Arg549His

p.R549H

Q86UU5

protein_coding

deleterious_low_confidence(0.04)

possibly_damaging(0.88)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

GGN

SNV

Missense_Mutation

c.1893N>G

p.Ile631Met

p.I631M

Q86UU5

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.975)

TCGA-EK-A2RJ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

GGN

SNV

Missense_Mutation

novel

c.1667N>A

p.Val556Glu

p.V556E

Q86UU5

protein_coding

deleterious_low_confidence(0.02)

possibly_damaging(0.702)

TCGA-VS-A9U6-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

GGN

insertion

In_Frame_Ins

novel

c.1104_1105insAGC

p.Gly368_Ala369insSer

p.G368_A369insS

Q86UU5

protein_coding

TCGA-DS-A1OC-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

gemcitabine

GGN

SNV

Missense_Mutation

c.698N>T

p.Ala233Val

p.A233V

Q86UU5

protein_coding

tolerated_low_confidence(0.38)

benign(0.005)

TCGA-AA-3710-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

GGN

SNV

Missense_Mutation

c.1648G>A

p.Glu550Lys

p.E550K

Q86UU5

protein_coding

tolerated_low_confidence(0.11)

benign(0.091)

TCGA-AA-3977-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

GGN

SNV

Missense_Mutation

c.52N>A

p.Gln18Lys

p.Q18K

Q86UU5

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.533)

TCGA-G4-6302-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

GGN

SNV

Missense_Mutation

c.1813N>T

p.Arg605Cys

p.R605C

Q86UU5

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.992)

TCGA-WS-AB45-01

Colorectum

colon adenocarcinoma

Female

<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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