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: GBP2

Gene summary for GBP2

Gene summary.

Gene information	Species	Human
	Gene symbol	GBP2
	Gene ID	2634
	Gene name	guanylate binding protein 2
	Gene Alias	GBP2
	Cytomap	1p22.2
	Gene Type	protein-coding
	GO ID	GO:0001562
	UniProtAcc	P32456

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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
2634	GBP2	GSM4909281	Human	Breast	IDC	1.10e-14	-4.55e-01	0.21
2634	GBP2	GSM4909282	Human	Breast	IDC	5.45e-10	-4.08e-01	-0.0288
2634	GBP2	GSM4909285	Human	Breast	IDC	1.30e-05	-3.36e-01	0.21
2634	GBP2	GSM4909286	Human	Breast	IDC	1.91e-31	-5.49e-01	0.1081
2634	GBP2	GSM4909287	Human	Breast	IDC	4.07e-02	-2.93e-01	0.2057
2634	GBP2	GSM4909290	Human	Breast	IDC	2.50e-10	-4.73e-01	0.2096
2634	GBP2	GSM4909291	Human	Breast	IDC	1.69e-07	-4.46e-01	0.1753
2634	GBP2	GSM4909292	Human	Breast	IDC	8.62e-03	-5.49e-01	0.1236
2634	GBP2	GSM4909293	Human	Breast	IDC	9.89e-11	-3.66e-01	0.1581
2634	GBP2	GSM4909294	Human	Breast	IDC	8.66e-13	-3.79e-01	0.2022
2634	GBP2	GSM4909296	Human	Breast	IDC	4.67e-23	-5.05e-01	0.1524
2634	GBP2	GSM4909297	Human	Breast	IDC	2.80e-18	-3.81e-01	0.1517
2634	GBP2	GSM4909298	Human	Breast	IDC	9.37e-12	-4.18e-01	0.1551
2634	GBP2	GSM4909301	Human	Breast	IDC	3.35e-30	-5.40e-01	0.1577
2634	GBP2	GSM4909302	Human	Breast	IDC	1.76e-13	-4.37e-01	0.1545
2634	GBP2	GSM4909304	Human	Breast	IDC	3.74e-26	-5.22e-01	0.1636
2634	GBP2	GSM4909306	Human	Breast	IDC	3.73e-11	-3.93e-01	0.1564
2634	GBP2	GSM4909307	Human	Breast	IDC	1.22e-13	-4.36e-01	0.1569
2634	GBP2	GSM4909308	Human	Breast	IDC	1.14e-18	-5.21e-01	0.158
2634	GBP2	GSM4909311	Human	Breast	IDC	5.30e-28	-4.83e-01	0.1534

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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:00713568	Breast	Precancer	cellular response to tumor necrosis factor	28/1080	229/18723	1.42e-04	2.45e-03	28
GO:00346128	Breast	Precancer	response to tumor necrosis factor	29/1080	253/18723	3.32e-04	4.70e-03	29
GO:007135613	Breast	IDC	cellular response to tumor necrosis factor	35/1434	229/18723	6.64e-05	1.35e-03	35
GO:003461213	Breast	IDC	response to tumor necrosis factor	36/1434	253/18723	2.29e-04	3.64e-03	36
GO:00343414	Breast	IDC	response to interferon-gamma	21/1434	141/18723	2.46e-03	2.22e-02	21
GO:007135622	Breast	DCIS	cellular response to tumor necrosis factor	33/1390	229/18723	1.84e-04	3.00e-03	33
GO:003461222	Breast	DCIS	response to tumor necrosis factor	33/1390	253/18723	1.11e-03	1.21e-02	33
GO:003434111	Breast	DCIS	response to interferon-gamma	20/1390	141/18723	3.83e-03	3.05e-02	20
GO:003450417	Esophagus	HGIN	protein localization to nucleus	84/2587	290/18723	1.06e-11	1.24e-09	84
GO:003450418	Esophagus	ESCC	protein localization to nucleus	211/8552	290/18723	4.06e-21	6.60e-19	211
GO:003461220	Esophagus	ESCC	response to tumor necrosis factor	149/8552	253/18723	1.47e-05	1.33e-04	149
GO:007135620	Esophagus	ESCC	cellular response to tumor necrosis factor	132/8552	229/18723	1.69e-04	1.11e-03	132
GO:00343418	Esophagus	ESCC	response to interferon-gamma	86/8552	141/18723	1.74e-04	1.14e-03	86
GO:00713466	Esophagus	ESCC	cellular response to interferon-gamma	69/8552	118/18723	3.44e-03	1.41e-02	69
GO:003450421	Liver	HCC	protein localization to nucleus	194/7958	290/18723	2.84e-17	2.85e-15	194
GO:00343411	Liver	HCC	response to interferon-gamma	82/7958	141/18723	1.25e-04	1.03e-03	82
GO:00713461	Liver	HCC	cellular response to interferon-gamma	70/7958	118/18723	1.66e-04	1.32e-03	70
GO:00705551	Liver	HCC	response to interleukin-1	80/7958	143/18723	7.95e-04	4.77e-03	80
GO:003461211	Liver	HCC	response to tumor necrosis factor	132/7958	253/18723	1.14e-03	6.48e-03	132
GO:00713471	Liver	HCC	cellular response to interleukin-1	61/7958	113/18723	8.98e-03	3.46e-02	61

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa046219	Esophagus	HGIN	NOD-like receptor signaling pathway	45/1383	186/8465	3.40e-03	2.54e-02	2.02e-02	45
hsa0462114	Esophagus	HGIN	NOD-like receptor signaling pathway	45/1383	186/8465	3.40e-03	2.54e-02	2.02e-02	45
hsa0462122	Esophagus	ESCC	NOD-like receptor signaling pathway	116/4205	186/8465	2.90e-04	1.03e-03	5.30e-04	116
hsa0462132	Esophagus	ESCC	NOD-like receptor signaling pathway	116/4205	186/8465	2.90e-04	1.03e-03	5.30e-04	116
hsa046218	Oral cavity	OSCC	NOD-like receptor signaling pathway	108/3704	186/8465	5.13e-05	2.07e-04	1.05e-04	108
hsa0462113	Oral cavity	OSCC	NOD-like receptor signaling pathway	108/3704	186/8465	5.13e-05	2.07e-04	1.05e-04	108
hsa046214	Oral cavity	EOLP	NOD-like receptor signaling pathway	48/1218	186/8465	2.51e-05	1.31e-04	7.70e-05	48
hsa046215	Oral cavity	EOLP	NOD-like receptor signaling pathway	48/1218	186/8465	2.51e-05	1.31e-04	7.70e-05	48
hsa046216	Oral cavity	NEOLP	NOD-like receptor signaling pathway	39/1112	186/8465	1.79e-03	7.91e-03	4.98e-03	39
hsa046217	Oral cavity	NEOLP	NOD-like receptor signaling pathway	39/1112	186/8465	1.79e-03	7.91e-03	4.98e-03	39

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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

GBP2

insertion

Nonsense_Mutation

novel

c.15_16insCATTAATGGGCTCTTTACATTGACTTTGGAGGATTACAGTCAACTG

p.Asn6HisfsTer2

p.N6Hfs*2

P32456

protein_coding

TCGA-A8-A097-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

GBP2

insertion

Frame_Shift_Ins

novel

c.750_751insGG

p.Leu251GlyfsTer2

p.L251Gfs*2

P32456

protein_coding

TCGA-AN-A0FX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

GBP2

insertion

Nonsense_Mutation

novel

c.748_749insTATAGTATCATCTCATATTCCTTGCA

p.Gln250LeufsTer2

p.Q250Lfs*2

P32456

protein_coding

TCGA-AN-A0FX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

GBP2

insertion

Frame_Shift_Ins

novel

c.3_4insT

p.Ala2CysfsTer14

p.A2Cfs*14

P32456

protein_coding

TCGA-BH-A0HY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

taxotere

GBP2

insertion

Frame_Shift_Ins

novel

c.2_3insTAATGGGCTCTTTACATTGACTTTGGAGGATTACA

p.Met1?

p.M1?

P32456

protein_coding

TCGA-BH-A0HY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

taxotere

GBP2

deletion

Frame_Shift_Del

novel

c.188delA

p.Asn63ThrfsTer5

p.N63Tfs*5

P32456

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

GBP2

SNV

Missense_Mutation

novel

c.568N>C

p.Asp190His

p.D190H

P32456

protein_coding

deleterious(0.05)

probably_damaging(0.939)

TCGA-C5-A2LZ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Unknown

GBP2

SNV

Missense_Mutation

novel

c.199N>G

p.Leu67Val

p.L67V

P32456

protein_coding

tolerated(0.16)

benign(0.028)

TCGA-MA-AA41-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

GBP2

SNV

Missense_Mutation

novel

c.1174N>A

p.Asp392Asn

p.D392N

P32456

protein_coding

tolerated(0.18)

benign(0.071)

TCGA-VS-A952-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

GBP2

SNV

Missense_Mutation

novel

c.1565N>G

p.Tyr522Cys

p.Y522C

P32456

protein_coding

deleterious(0)

probably_damaging(0.985)

TCGA-AA-3984-01

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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