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: PLCG2

Gene summary for PLCG2

Gene summary.

Gene information	Species	Human
	Gene symbol	PLCG2
	Gene ID	5336
	Gene name	phospholipase C gamma 2
	Gene Alias	APLAID
	Cytomap	16q23.3
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	P16885

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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
5336	PLCG2	GSM4909281	Human	Breast	IDC	1.27e-11	-7.37e-01	0.21
5336	PLCG2	GSM4909282	Human	Breast	IDC	6.43e-05	-6.33e-01	-0.0288
5336	PLCG2	GSM4909285	Human	Breast	IDC	1.77e-06	-7.08e-01	0.21
5336	PLCG2	GSM4909286	Human	Breast	IDC	2.70e-11	-7.24e-01	0.1081
5336	PLCG2	GSM4909290	Human	Breast	IDC	4.02e-03	-6.25e-01	0.2096
5336	PLCG2	GSM4909291	Human	Breast	IDC	7.46e-05	-7.18e-01	0.1753
5336	PLCG2	GSM4909293	Human	Breast	IDC	2.29e-10	-4.40e-01	0.1581
5336	PLCG2	GSM4909294	Human	Breast	IDC	3.75e-02	-5.17e-01	0.2022
5336	PLCG2	GSM4909297	Human	Breast	IDC	1.35e-08	-6.76e-01	0.1517
5336	PLCG2	GSM4909298	Human	Breast	IDC	4.73e-11	-7.27e-01	0.1551
5336	PLCG2	GSM4909299	Human	Breast	IDC	1.60e-06	-6.56e-01	0.035
5336	PLCG2	GSM4909301	Human	Breast	IDC	2.38e-03	-5.93e-01	0.1577
5336	PLCG2	GSM4909302	Human	Breast	IDC	3.54e-08	-6.85e-01	0.1545
5336	PLCG2	GSM4909304	Human	Breast	IDC	1.46e-05	-6.03e-01	0.1636
5336	PLCG2	GSM4909305	Human	Breast	IDC	8.81e-04	-6.58e-01	0.0436
5336	PLCG2	GSM4909306	Human	Breast	IDC	1.31e-09	-7.19e-01	0.1564
5336	PLCG2	GSM4909307	Human	Breast	IDC	2.38e-08	-7.11e-01	0.1569
5336	PLCG2	GSM4909308	Human	Breast	IDC	2.44e-09	-7.29e-01	0.158
5336	PLCG2	GSM4909311	Human	Breast	IDC	4.61e-06	-6.01e-01	0.1534
5336	PLCG2	GSM4909312	Human	Breast	IDC	1.66e-11	-7.39e-01	0.1552

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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
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
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:00100389	Breast	Precancer	response to metal ion	47/1080	373/18723	3.88e-07	1.79e-05	47
GO:00432549	Breast	Precancer	regulation of protein-containing complex assembly	50/1080	428/18723	1.63e-06	5.97e-05	50
GO:00313349	Breast	Precancer	positive regulation of protein-containing complex assembly	33/1080	237/18723	2.39e-06	8.21e-05	33
GO:00018196	Breast	Precancer	positive regulation of cytokine production	52/1080	467/18723	4.18e-06	1.29e-04	52
GO:00420609	Breast	Precancer	wound healing	48/1080	422/18723	5.48e-06	1.63e-04	48
GO:00512358	Breast	Precancer	maintenance of location	40/1080	327/18723	5.85e-06	1.71e-04	40
GO:00516519	Breast	Precancer	maintenance of location in cell	30/1080	214/18723	5.91e-06	1.71e-04	30
GO:00022378	Breast	Precancer	response to molecule of bacterial origin	43/1080	363/18723	6.05e-06	1.72e-04	43
GO:00507293	Breast	Precancer	positive regulation of inflammatory response	23/1080	142/18723	6.51e-06	1.81e-04	23
GO:00324968	Breast	Precancer	response to lipopolysaccharide	41/1080	343/18723	7.94e-06	2.17e-04	41
GO:0050727	Breast	Precancer	regulation of inflammatory response	44/1080	386/18723	1.26e-05	3.22e-04	44
GO:00106348	Breast	Precancer	positive regulation of epithelial cell migration	25/1080	176/18723	2.75e-05	6.21e-04	25
GO:00321034	Breast	Precancer	positive regulation of response to external stimulus	46/1080	427/18723	3.41e-05	7.40e-04	46
GO:00106319	Breast	Precancer	epithelial cell migration	40/1080	357/18723	4.57e-05	9.71e-04	40
GO:00725938	Breast	Precancer	reactive oxygen species metabolic process	30/1080	239/18723	5.13e-05	1.07e-03	30
GO:00901329	Breast	Precancer	epithelium migration	40/1080	360/18723	5.51e-05	1.14e-03	40
GO:00313493	Breast	Precancer	positive regulation of defense response	33/1080	278/18723	6.79e-05	1.36e-03	33
GO:00901309	Breast	Precancer	tissue migration	40/1080	365/18723	7.48e-05	1.47e-03	40
GO:00508789	Breast	Precancer	regulation of body fluid levels	40/1080	379/18723	1.68e-04	2.77e-03	40
GO:00106329	Breast	Precancer	regulation of epithelial cell migration	33/1080	292/18723	1.74e-04	2.86e-03	33

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0517118	Breast	Precancer	Coronavirus disease - COVID-19	81/684	232/8465	3.74e-32	2.36e-30	1.81e-30	81
hsa0513118	Breast	Precancer	Shigellosis	44/684	247/8465	3.91e-07	6.86e-06	5.26e-06	44
hsa0516718	Breast	Precancer	Kaposi sarcoma-associated herpesvirus infection	36/684	194/8465	1.68e-06	2.53e-05	1.94e-05	36
hsa0516918	Breast	Precancer	Epstein-Barr virus infection	35/684	202/8465	1.15e-05	1.26e-04	9.64e-05	35
hsa0406616	Breast	Precancer	HIF-1 signaling pathway	23/684	109/8465	1.51e-05	1.59e-04	1.22e-04	23
hsa0511014	Breast	Precancer	Vibrio cholerae infection	14/684	50/8465	2.67e-05	2.64e-04	2.02e-04	14
hsa0467018	Breast	Precancer	Leukocyte transendothelial migration	20/684	114/8465	7.26e-04	5.33e-03	4.09e-03	20
hsa0520514	Breast	Precancer	Proteoglycans in cancer	30/684	205/8465	1.00e-03	7.18e-03	5.50e-03	30
hsa0517119	Breast	Precancer	Coronavirus disease - COVID-19	81/684	232/8465	3.74e-32	2.36e-30	1.81e-30	81
hsa0513119	Breast	Precancer	Shigellosis	44/684	247/8465	3.91e-07	6.86e-06	5.26e-06	44
hsa0516719	Breast	Precancer	Kaposi sarcoma-associated herpesvirus infection	36/684	194/8465	1.68e-06	2.53e-05	1.94e-05	36
hsa0516919	Breast	Precancer	Epstein-Barr virus infection	35/684	202/8465	1.15e-05	1.26e-04	9.64e-05	35
hsa0406617	Breast	Precancer	HIF-1 signaling pathway	23/684	109/8465	1.51e-05	1.59e-04	1.22e-04	23
hsa0511015	Breast	Precancer	Vibrio cholerae infection	14/684	50/8465	2.67e-05	2.64e-04	2.02e-04	14
hsa0467019	Breast	Precancer	Leukocyte transendothelial migration	20/684	114/8465	7.26e-04	5.33e-03	4.09e-03	20
hsa0520515	Breast	Precancer	Proteoglycans in cancer	30/684	205/8465	1.00e-03	7.18e-03	5.50e-03	30
hsa0517124	Breast	IDC	Coronavirus disease - COVID-19	86/867	232/8465	1.50e-28	9.72e-27	7.27e-27	86
hsa0516922	Breast	IDC	Epstein-Barr virus infection	45/867	202/8465	3.16e-07	6.05e-06	4.52e-06	45
hsa0511022	Breast	IDC	Vibrio cholerae infection	17/867	50/8465	4.82e-06	6.82e-05	5.10e-05	17
hsa0520523	Breast	IDC	Proteoglycans in cancer	42/867	205/8465	7.69e-06	9.99e-05	7.48e-05	42

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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

PLCG2

SNV

Missense_Mutation

c.2901N>G

p.Ile967Met

p.I967M

P16885

protein_coding

tolerated(0.23)

benign(0.077)

TCGA-A8-A0A7-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PLCG2

SNV

Missense_Mutation

novel

c.823G>T

p.Asp275Tyr

p.D275Y

P16885

protein_coding

deleterious(0.02)

benign(0.277)

TCGA-AC-A8OQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PLCG2

SNV

Missense_Mutation

rs201647862

c.3127N>G

p.Met1043Val

p.M1043V

P16885

protein_coding

deleterious(0.04)

benign(0.055)

TCGA-C8-A1HK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PLCG2

SNV

Missense_Mutation

c.2085C>G

p.Ile695Met

p.I695M

P16885

protein_coding

deleterious(0)

probably_damaging(0.973)

TCGA-D8-A1JA-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

PLCG2

SNV

Missense_Mutation

rs762414923

c.2149N>A

p.Val717Ile

p.V717I

P16885

protein_coding

tolerated(0.35)

probably_damaging(0.994)

TCGA-GM-A2DB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxol

PLCG2

SNV

Missense_Mutation

rs749548361

c.1328N>T

p.Ser443Leu

p.S443L

P16885

protein_coding

deleterious(0)

possibly_damaging(0.764)

TCGA-PE-A5DE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

PLCG2

insertion

Frame_Shift_Ins

novel

c.3412_3413insTGCTTCTT

p.Glu1138ValfsTer33

p.E1138Vfs*33

P16885

protein_coding

TCGA-A2-A0EQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

PLCG2

insertion

Frame_Shift_Ins

novel

c.3413_3414insCCTGATGTATCTACTGC

p.Glu1138AspfsTer36

p.E1138Dfs*36

P16885

protein_coding

TCGA-A2-A0EQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

PLCG2

insertion

Frame_Shift_Ins

novel

c.865_866insGCTTCATACTAACAAACGTAAAGAGCTATCATAGGGC

p.Glu289GlyfsTer28

p.E289Gfs*28

P16885

protein_coding

TCGA-A8-A07R-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Ancillary

zoledronic

PLCG2

insertion

Nonsense_Mutation

novel

c.2428_2429insGCTAACACTATTGAGTATTT

p.Asp810GlyfsTer2

p.D810Gfs*2

P16885

protein_coding

TCGA-BH-A0EE-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

docetaxel

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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
5336	PLCG2	DRUGGABLE GENOME, ENZYME, CLINICALLY ACTIONABLE, PHOSPHOLIPASE	inhibitor	252827477
5336	PLCG2	DRUGGABLE GENOME, ENZYME, CLINICALLY ACTIONABLE, PHOSPHOLIPASE		IBRUTINIB	IBRUTINIB	24869598

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