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: GNB2

Gene summary for GNB2

Gene summary.

Gene information	Species	Human
	Gene symbol	GNB2
	Gene ID	2783
	Gene name	G protein subunit beta 2
	Gene Alias	SSS4
	Cytomap	7q22.1
	Gene Type	protein-coding
	GO ID	GO:0007154
	UniProtAcc	P62879

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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
2783	GNB2	GSM4909282	Human	Breast	IDC	1.43e-43	7.03e-01	-0.0288
2783	GNB2	GSM4909294	Human	Breast	IDC	2.90e-02	6.94e-02	0.2022
2783	GNB2	GSM4909296	Human	Breast	IDC	5.26e-09	3.45e-02	0.1524
2783	GNB2	GSM4909297	Human	Breast	IDC	3.55e-12	-9.02e-02	0.1517
2783	GNB2	GSM4909298	Human	Breast	IDC	9.42e-03	2.51e-01	0.1551
2783	GNB2	GSM4909304	Human	Breast	IDC	2.68e-30	6.00e-01	0.1636
2783	GNB2	GSM4909311	Human	Breast	IDC	7.10e-27	-3.49e-01	0.1534
2783	GNB2	GSM4909312	Human	Breast	IDC	2.45e-11	-2.54e-01	0.1552
2783	GNB2	GSM4909315	Human	Breast	IDC	8.13e-20	5.60e-01	0.21
2783	GNB2	GSM4909316	Human	Breast	IDC	1.29e-20	6.56e-01	0.21
2783	GNB2	GSM4909318	Human	Breast	IDC	4.44e-04	3.35e-01	0.2031
2783	GNB2	GSM4909319	Human	Breast	IDC	5.95e-41	-1.02e-01	0.1563
2783	GNB2	GSM4909320	Human	Breast	IDC	1.05e-08	-2.94e-01	0.1575
2783	GNB2	GSM4909321	Human	Breast	IDC	1.82e-16	7.93e-02	0.1559
2783	GNB2	brca1	Human	Breast	Precancer	9.42e-09	3.28e-01	-0.0338
2783	GNB2	brca2	Human	Breast	Precancer	2.30e-02	2.62e-01	-0.024
2783	GNB2	brca3	Human	Breast	Precancer	9.65e-07	2.62e-01	-0.0263
2783	GNB2	M2	Human	Breast	IDC	3.99e-13	5.82e-01	0.21
2783	GNB2	NCCBC14	Human	Breast	DCIS	1.98e-11	9.36e-02	0.2021
2783	GNB2	NCCBC2	Human	Breast	DCIS	3.73e-05	-2.95e-02	0.1554

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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
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
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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
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

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0516718	Breast	Precancer	Kaposi sarcoma-associated herpesvirus infection	36/684	194/8465	1.68e-06	2.53e-05	1.94e-05	36
hsa0472316	Breast	Precancer	Retrograde endocannabinoid signaling	25/684	148/8465	3.05e-04	2.47e-03	1.89e-03	25
hsa0516316	Breast	Precancer	Human cytomegalovirus infection	32/684	225/8465	1.13e-03	7.57e-03	5.80e-03	32
hsa0516719	Breast	Precancer	Kaposi sarcoma-associated herpesvirus infection	36/684	194/8465	1.68e-06	2.53e-05	1.94e-05	36
hsa0472317	Breast	Precancer	Retrograde endocannabinoid signaling	25/684	148/8465	3.05e-04	2.47e-03	1.89e-03	25
hsa0516317	Breast	Precancer	Human cytomegalovirus infection	32/684	225/8465	1.13e-03	7.57e-03	5.80e-03	32
hsa0516723	Breast	IDC	Kaposi sarcoma-associated herpesvirus infection	38/867	194/8465	5.87e-05	5.96e-04	4.46e-04	38
hsa0472323	Breast	IDC	Retrograde endocannabinoid signaling	31/867	148/8465	7.62e-05	7.50e-04	5.61e-04	31
hsa0516324	Breast	IDC	Human cytomegalovirus infection	39/867	225/8465	6.66e-04	5.41e-03	4.05e-03	39
hsa0517014	Breast	IDC	Human immunodeficiency virus 1 infection	33/867	212/8465	9.28e-03	4.37e-02	3.27e-02	33
hsa0516733	Breast	IDC	Kaposi sarcoma-associated herpesvirus infection	38/867	194/8465	5.87e-05	5.96e-04	4.46e-04	38
hsa0472333	Breast	IDC	Retrograde endocannabinoid signaling	31/867	148/8465	7.62e-05	7.50e-04	5.61e-04	31
hsa0516334	Breast	IDC	Human cytomegalovirus infection	39/867	225/8465	6.66e-04	5.41e-03	4.05e-03	39
hsa0517015	Breast	IDC	Human immunodeficiency virus 1 infection	33/867	212/8465	9.28e-03	4.37e-02	3.27e-02	33
hsa0516743	Breast	DCIS	Kaposi sarcoma-associated herpesvirus infection	38/846	194/8465	3.43e-05	3.69e-04	2.72e-04	38
hsa0472342	Breast	DCIS	Retrograde endocannabinoid signaling	29/846	148/8465	2.82e-04	2.34e-03	1.72e-03	29
hsa0516344	Breast	DCIS	Human cytomegalovirus infection	38/846	225/8465	8.11e-04	5.95e-03	4.38e-03	38
hsa0517024	Breast	DCIS	Human immunodeficiency virus 1 infection	33/846	212/8465	6.49e-03	3.22e-02	2.37e-02	33
hsa0516753	Breast	DCIS	Kaposi sarcoma-associated herpesvirus infection	38/846	194/8465	3.43e-05	3.69e-04	2.72e-04	38
hsa0472352	Breast	DCIS	Retrograde endocannabinoid signaling	29/846	148/8465	2.82e-04	2.34e-03	1.72e-03	29

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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

GNB2

SNV

Missense_Mutation

c.922N>T

p.Leu308Phe

p.L308F

P62879

protein_coding

deleterious(0.01)

probably_damaging(0.999)

TCGA-C8-A26W-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

GNB2

insertion

Frame_Shift_Ins

novel

c.235_236insCAGGGCAGGATCACTTGAGCTCAGGAGTT

p.Leu79ProfsTer32

p.L79Pfs*32

P62879

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

GNB2

insertion

Frame_Shift_Ins

novel

c.193_194insTGTTCTCTTCTCTCCCTTTCCTC

p.Thr65MetfsTer44

p.T65Mfs*44

P62879

protein_coding

TCGA-BH-A0B1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

adriamycin

GNB2

SNV

Missense_Mutation

rs760148387

c.964G>A

p.Asp322Asn

p.D322N

P62879

protein_coding

tolerated(0.17)

benign(0.217)

TCGA-FU-A3HZ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

GNB2

SNV

Missense_Mutation

c.955G>A

p.Gly319Arg

p.G319R

P62879

protein_coding

tolerated(0.33)

probably_damaging(1)

TCGA-DM-A1DB-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

GNB2

SNV

Missense_Mutation

c.449G>A

p.Arg150His

p.R150H

P62879

protein_coding

deleterious(0.02)

probably_damaging(0.999)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

GNB2

SNV

Missense_Mutation

c.449G>A

p.Arg150His

p.R150H

P62879

protein_coding

deleterious(0.02)

probably_damaging(0.999)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

GNB2

SNV

Missense_Mutation

novel

c.766N>T

p.Arg256Trp

p.R256W

P62879

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-AJ-A3EK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

GNB2

SNV

Missense_Mutation

c.217N>A

p.Ala73Thr

p.A73T

P62879

protein_coding

deleterious(0)

probably_damaging(0.971)

TCGA-AJ-A3OK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Chemotherapy

carboplatin

GNB2

SNV

Missense_Mutation

c.682G>A

p.Asp228Asn

p.D228N

P62879

protein_coding

deleterious(0)

possibly_damaging(0.818)

TCGA-AX-A2HC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

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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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