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: GAB2

Gene summary for GAB2

Gene summary.

Gene information	Species	Human
	Gene symbol	GAB2
	Gene ID	9846
	Gene name	GRB2 associated binding protein 2
	Gene Alias	GAB2
	Cytomap	11q14.1
	Gene Type	protein-coding
	GO ID	GO:0001775
	UniProtAcc	Q9UQC2

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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
9846	GAB2	HTA11_3410_2000001011	Human	Colorectum	AD	1.24e-10	-4.90e-01	0.0155
9846	GAB2	HTA11_2487_2000001011	Human	Colorectum	SER	3.06e-03	-4.11e-01	-0.1808
9846	GAB2	HTA11_1938_2000001011	Human	Colorectum	AD	5.34e-03	-3.79e-01	-0.0811
9846	GAB2	HTA11_78_2000001011	Human	Colorectum	AD	1.13e-06	-4.32e-01	-0.1088
9846	GAB2	HTA11_3361_2000001011	Human	Colorectum	AD	5.07e-04	-5.05e-01	-0.1207
9846	GAB2	HTA11_696_2000001011	Human	Colorectum	AD	3.66e-08	-4.07e-01	-0.1464
9846	GAB2	HTA11_866_2000001011	Human	Colorectum	AD	1.91e-04	-4.09e-01	-0.1001
9846	GAB2	HTA11_866_3004761011	Human	Colorectum	AD	8.03e-08	-4.36e-01	0.096
9846	GAB2	HTA11_10711_2000001011	Human	Colorectum	AD	7.00e-06	-5.20e-01	0.0338
9846	GAB2	HTA11_7696_3000711011	Human	Colorectum	AD	1.14e-14	-5.16e-01	0.0674
9846	GAB2	HTA11_6818_2000001021	Human	Colorectum	AD	5.27e-04	-3.74e-01	0.0588
9846	GAB2	HTA11_99999970781_79442	Human	Colorectum	MSS	4.53e-12	-4.65e-01	0.294
9846	GAB2	HTA11_99999965104_69814	Human	Colorectum	MSS	1.60e-02	-4.11e-01	0.281
9846	GAB2	HTA11_99999971662_82457	Human	Colorectum	MSS	6.18e-07	-3.77e-01	0.3859
9846	GAB2	HTA11_99999973899_84307	Human	Colorectum	MSS	1.11e-03	-4.96e-01	0.2585
9846	GAB2	HTA11_99999974143_84620	Human	Colorectum	MSS	2.08e-22	-6.29e-01	0.3005
9846	GAB2	F007	Human	Colorectum	FAP	2.10e-03	-3.15e-01	0.1176
9846	GAB2	A001-C-207	Human	Colorectum	FAP	4.28e-03	-1.58e-01	0.1278
9846	GAB2	A015-C-203	Human	Colorectum	FAP	1.65e-28	-5.04e-01	-0.1294
9846	GAB2	A015-C-204	Human	Colorectum	FAP	1.83e-06	-3.35e-01	-0.0228

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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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
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

∗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:0051656	Colorectum	AD	establishment of organelle localization	131/3918	390/18723	3.00e-09	2.06e-07	131
GO:0030099	Colorectum	AD	myeloid cell differentiation	119/3918	381/18723	1.24e-06	4.01e-05	119
GO:0045921	Colorectum	AD	positive regulation of exocytosis	33/3918	86/18723	1.58e-04	2.20e-03	33
GO:0051047	Colorectum	AD	positive regulation of secretion	90/3918	310/18723	4.11e-04	4.66e-03	90
GO:1903532	Colorectum	AD	positive regulation of secretion by cell	82/3918	282/18723	6.85e-04	7.00e-03	82
GO:0006887	Colorectum	AD	exocytosis	96/3918	352/18723	2.48e-03	1.90e-02	96
GO:0017157	Colorectum	AD	regulation of exocytosis	59/3918	202/18723	3.20e-03	2.36e-02	59
GO:0002573	Colorectum	AD	myeloid leukocyte differentiation	60/3918	208/18723	4.03e-03	2.81e-02	60
GO:0048017	Colorectum	AD	inositol lipid-mediated signaling	53/3918	182/18723	5.35e-03	3.52e-02	53
GO:0048015	Colorectum	AD	phosphatidylinositol-mediated signaling	52/3918	178/18723	5.37e-03	3.54e-02	52
GO:00516561	Colorectum	SER	establishment of organelle localization	100/2897	390/18723	1.11e-07	6.79e-06	100
GO:00459211	Colorectum	SER	positive regulation of exocytosis	25/2897	86/18723	9.88e-04	1.17e-02	25
GO:00068871	Colorectum	SER	exocytosis	75/2897	352/18723	2.05e-03	2.03e-02	75
GO:00300991	Colorectum	SER	myeloid cell differentiation	80/2897	381/18723	2.28e-03	2.18e-02	80
GO:00480171	Colorectum	SER	inositol lipid-mediated signaling	42/2897	182/18723	4.36e-03	3.49e-02	42
GO:00480151	Colorectum	SER	phosphatidylinositol-mediated signaling	41/2897	178/18723	4.97e-03	3.86e-02	41
GO:00510471	Colorectum	SER	positive regulation of secretion	65/2897	310/18723	5.71e-03	4.19e-02	65
GO:00171571	Colorectum	SER	regulation of exocytosis	45/2897	202/18723	6.46e-03	4.63e-02	45
GO:00516562	Colorectum	MSS	establishment of organelle localization	115/3467	390/18723	7.30e-08	3.67e-06	115
GO:00300992	Colorectum	MSS	myeloid cell differentiation	110/3467	381/18723	4.48e-07	1.75e-05	110

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa04666	Colorectum	AD	Fc gamma R-mediated phagocytosis	46/2092	97/8465	9.10e-07	1.22e-05	7.77e-06	46
hsa05220	Colorectum	AD	Chronic myeloid leukemia	31/2092	76/8465	1.41e-03	8.46e-03	5.39e-03	31
hsa04071	Colorectum	AD	Sphingolipid signaling pathway	43/2092	121/8465	4.83e-03	2.28e-02	1.45e-02	43
hsa046661	Colorectum	AD	Fc gamma R-mediated phagocytosis	46/2092	97/8465	9.10e-07	1.22e-05	7.77e-06	46
hsa052201	Colorectum	AD	Chronic myeloid leukemia	31/2092	76/8465	1.41e-03	8.46e-03	5.39e-03	31
hsa040711	Colorectum	AD	Sphingolipid signaling pathway	43/2092	121/8465	4.83e-03	2.28e-02	1.45e-02	43
hsa046662	Colorectum	SER	Fc gamma R-mediated phagocytosis	39/1580	97/8465	5.84e-07	9.70e-06	7.04e-06	39
hsa046663	Colorectum	SER	Fc gamma R-mediated phagocytosis	39/1580	97/8465	5.84e-07	9.70e-06	7.04e-06	39
hsa046664	Colorectum	MSS	Fc gamma R-mediated phagocytosis	45/1875	97/8465	9.30e-08	1.56e-06	9.55e-07	45
hsa052202	Colorectum	MSS	Chronic myeloid leukemia	29/1875	76/8465	1.10e-03	6.27e-03	3.84e-03	29
hsa040712	Colorectum	MSS	Sphingolipid signaling pathway	40/1875	121/8465	3.56e-03	1.64e-02	1.01e-02	40
hsa046665	Colorectum	MSS	Fc gamma R-mediated phagocytosis	45/1875	97/8465	9.30e-08	1.56e-06	9.55e-07	45
hsa052203	Colorectum	MSS	Chronic myeloid leukemia	29/1875	76/8465	1.10e-03	6.27e-03	3.84e-03	29
hsa040713	Colorectum	MSS	Sphingolipid signaling pathway	40/1875	121/8465	3.56e-03	1.64e-02	1.01e-02	40
hsa046666	Colorectum	FAP	Fc gamma R-mediated phagocytosis	35/1404	97/8465	2.46e-06	4.28e-05	2.60e-05	35
hsa040714	Colorectum	FAP	Sphingolipid signaling pathway	34/1404	121/8465	9.53e-04	5.22e-03	3.17e-03	34
hsa052204	Colorectum	FAP	Chronic myeloid leukemia	23/1404	76/8465	2.14e-03	1.05e-02	6.39e-03	23
hsa046667	Colorectum	FAP	Fc gamma R-mediated phagocytosis	35/1404	97/8465	2.46e-06	4.28e-05	2.60e-05	35
hsa040715	Colorectum	FAP	Sphingolipid signaling pathway	34/1404	121/8465	9.53e-04	5.22e-03	3.17e-03	34
hsa052205	Colorectum	FAP	Chronic myeloid leukemia	23/1404	76/8465	2.14e-03	1.05e-02	6.39e-03	23

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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

GAB2

SNV

Missense_Mutation

rs772467341

c.350N>A

p.Gly117Asp

p.G117D

Q9UQC2

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-A8-A06X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

GAB2

SNV

Missense_Mutation

rs201966341

c.1978G>C

p.Glu660Gln

p.E660Q

Q9UQC2

protein_coding

tolerated(0.12)

probably_damaging(0.986)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

GAB2

insertion

Nonsense_Mutation

novel

c.1184_1185insAAATTCAGAAGATCAGTCCAAACTGGAGTGAAACCTGTGTG

p.Met395IlefsTer11

p.M395Ifs*11

Q9UQC2

protein_coding

TCGA-A2-A0T2-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

xeloda

GAB2

insertion

In_Frame_Ins

novel

c.1157_1158insACTCCGTTTTGGAACTGAGATGATAAAGACATACATAAAACA

p.Ile386_Pro387insLeuArgPheGlyThrGluMetIleLysThrTyrIleLysHis

p.I386_P387insLRFGTEMIKTYIKH

Q9UQC2

protein_coding

TCGA-A8-A09W-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

GAB2

insertion

Frame_Shift_Ins

novel

c.707_708insACCTGATCGGAAAGGTAAGTCC

p.His236GlnfsTer22

p.H236Qfs*22

Q9UQC2

protein_coding

TCGA-BH-A0AY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

GAB2

SNV

Missense_Mutation

rs778004853

c.1505N>T

p.Pro502Leu

p.P502L

Q9UQC2

protein_coding

tolerated(0.09)

benign(0.001)

TCGA-EA-A5ZF-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

GAB2

SNV

Missense_Mutation

novel

c.1012N>A

p.Ala338Thr

p.A338T

Q9UQC2

protein_coding

tolerated(0.3)

benign(0.012)

TCGA-Q1-A5R1-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

GAB2

SNV

Missense_Mutation

novel

c.1144N>T

p.Val382Phe

p.V382F

Q9UQC2

protein_coding

tolerated(0.66)

benign(0.049)

TCGA-ZJ-AAXA-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

GAB2

SNV

Missense_Mutation

novel

c.1139N>T

p.Arg380Ile

p.R380I

Q9UQC2

protein_coding

tolerated(0.28)

benign(0.035)

TCGA-5M-AAT4-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Unknown

GAB2

SNV

Missense_Mutation

novel

c.1769N>G

p.Pro590Arg

p.P590R

Q9UQC2

protein_coding

deleterious(0.03)

probably_damaging(0.998)

TCGA-AA-3861-01

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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