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: PLPP2

Gene summary for PLPP2

Gene summary.

Gene information	Species	Human
	Gene symbol	PLPP2
	Gene ID	8612
	Gene name	phospholipid phosphatase 2
	Gene Alias	LPP2
	Cytomap	19p13.3
	Gene Type	protein-coding
	GO ID	GO:0006066
	UniProtAcc	O43688

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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
8612	PLPP2	HTA11_2487_2000001011	Human	Colorectum	SER	2.97e-07	3.78e-01	-0.1808
8612	PLPP2	HTA11_1938_2000001011	Human	Colorectum	AD	1.87e-09	5.29e-01	-0.0811
8612	PLPP2	HTA11_347_2000001011	Human	Colorectum	AD	5.85e-13	4.19e-01	-0.1954
8612	PLPP2	HTA11_696_2000001011	Human	Colorectum	AD	9.09e-04	3.53e-01	-0.1464
8612	PLPP2	HTA11_1391_2000001011	Human	Colorectum	AD	3.28e-15	6.96e-01	-0.059
8612	PLPP2	HTA11_546_2000001011	Human	Colorectum	AD	7.74e-03	3.60e-01	-0.0842
8612	PLPP2	HTA11_866_3004761011	Human	Colorectum	AD	6.23e-10	4.07e-01	0.096
8612	PLPP2	HTA11_7663_2000001011	Human	Colorectum	SER	2.37e-04	6.41e-01	0.0131
8612	PLPP2	HTA11_10711_2000001011	Human	Colorectum	AD	9.17e-09	4.31e-01	0.0338
8612	PLPP2	HTA11_7696_3000711011	Human	Colorectum	AD	3.15e-08	4.23e-01	0.0674
8612	PLPP2	HTA11_6818_2000001011	Human	Colorectum	AD	1.22e-06	5.82e-01	0.0112
8612	PLPP2	HTA11_6818_2000001021	Human	Colorectum	AD	3.78e-17	7.64e-01	0.0588
8612	PLPP2	HTA11_99999970781_79442	Human	Colorectum	MSS	7.03e-03	2.54e-01	0.294
8612	PLPP2	HTA11_99999965062_69753	Human	Colorectum	MSI-H	3.26e-03	1.05e+00	0.3487
8612	PLPP2	HTA11_99999971662_82457	Human	Colorectum	MSS	6.31e-15	6.86e-01	0.3859
8612	PLPP2	A002-C-116	Human	Colorectum	FAP	6.87e-03	-1.02e-01	-0.0452
8612	PLPP2	LZE2T	Human	Esophagus	ESCC	1.66e-03	9.92e-01	0.082
8612	PLPP2	LZE4T	Human	Esophagus	ESCC	8.74e-20	9.37e-01	0.0811
8612	PLPP2	LZE5T	Human	Esophagus	ESCC	1.77e-09	1.27e+00	0.0514
8612	PLPP2	LZE7T	Human	Esophagus	ESCC	1.59e-03	4.16e-01	0.0667

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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
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
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:0016311	Colorectum	AD	dephosphorylation	123/3918	417/18723	1.84e-05	3.82e-04	123
GO:0006066	Colorectum	AD	alcohol metabolic process	106/3918	353/18723	3.02e-05	5.57e-04	106
GO:0030258	Colorectum	AD	lipid modification	67/3918	212/18723	1.66e-04	2.27e-03	67
GO:0006644	Colorectum	AD	phospholipid metabolic process	101/3918	383/18723	5.80e-03	3.67e-02	101
GO:00060661	Colorectum	SER	alcohol metabolic process	79/2897	353/18723	3.50e-04	5.50e-03	79
GO:00163111	Colorectum	SER	dephosphorylation	86/2897	417/18723	2.73e-03	2.46e-02	86
GO:00066441	Colorectum	SER	phospholipid metabolic process	79/2897	383/18723	3.94e-03	3.24e-02	79
GO:00302581	Colorectum	SER	lipid modification	47/2897	212/18723	6.01e-03	4.38e-02	47
GO:00060662	Colorectum	MSS	alcohol metabolic process	92/3467	353/18723	2.57e-04	3.46e-03	92
GO:00302582	Colorectum	MSS	lipid modification	57/3467	212/18723	1.64e-03	1.49e-02	57
GO:00163112	Colorectum	MSS	dephosphorylation	101/3467	417/18723	1.98e-03	1.70e-02	101
GO:0034311	Colorectum	MSI-H	diol metabolic process	7/1319	29/18723	3.34e-03	4.05e-02	7
GO:00163113	Colorectum	FAP	dephosphorylation	95/2622	417/18723	7.07e-07	3.32e-05	95
GO:00302583	Colorectum	FAP	lipid modification	52/2622	212/18723	2.84e-05	6.49e-04	52
GO:00066442	Colorectum	FAP	phospholipid metabolic process	74/2622	383/18723	2.24e-03	1.83e-02	74
GO:00060663	Colorectum	FAP	alcohol metabolic process	69/2622	353/18723	2.29e-03	1.85e-02	69
GO:0046519	Colorectum	FAP	sphingoid metabolic process	8/2622	21/18723	5.43e-03	3.53e-02	8
GO:00448437	Esophagus	HGIN	cell cycle G1/S phase transition	52/2587	241/18723	6.19e-04	8.58e-03	52
GO:19028065	Esophagus	HGIN	regulation of cell cycle G1/S phase transition	39/2587	168/18723	6.60e-04	9.03e-03	39
GO:19019876	Esophagus	HGIN	regulation of cell cycle phase transition	72/2587	390/18723	5.78e-03	4.70e-02	72

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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
hsa00561	Colorectum	AD	Glycerolipid metabolism	24/2092	63/8465	1.25e-02	4.54e-02	2.90e-02	24
hsa046661	Colorectum	AD	Fc gamma R-mediated phagocytosis	46/2092	97/8465	9.10e-07	1.22e-05	7.77e-06	46
hsa005611	Colorectum	AD	Glycerolipid metabolism	24/2092	63/8465	1.25e-02	4.54e-02	2.90e-02	24
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
hsa05231	Colorectum	MSS	Choline metabolism in cancer	34/1875	98/8465	2.90e-03	1.39e-02	8.50e-03	34
hsa005612	Colorectum	MSS	Glycerolipid metabolism	23/1875	63/8465	6.55e-03	2.64e-02	1.62e-02	23
hsa046665	Colorectum	MSS	Fc gamma R-mediated phagocytosis	45/1875	97/8465	9.30e-08	1.56e-06	9.55e-07	45
hsa052311	Colorectum	MSS	Choline metabolism in cancer	34/1875	98/8465	2.90e-03	1.39e-02	8.50e-03	34
hsa005613	Colorectum	MSS	Glycerolipid metabolism	23/1875	63/8465	6.55e-03	2.64e-02	1.62e-02	23
hsa052312	Colorectum	FAP	Choline metabolism in cancer	29/1404	98/8465	9.03e-04	5.20e-03	3.16e-03	29
hsa052313	Colorectum	FAP	Choline metabolism in cancer	29/1404	98/8465	9.03e-04	5.20e-03	3.16e-03	29
hsa0466620	Esophagus	ESCC	Fc gamma R-mediated phagocytosis	63/4205	97/8465	1.63e-03	4.89e-03	2.50e-03	63
hsa006003	Esophagus	ESCC	Sphingolipid metabolism	36/4205	53/8465	5.41e-03	1.36e-02	6.99e-03	36
hsa052319	Esophagus	ESCC	Choline metabolism in cancer	61/4205	98/8465	7.97e-03	1.92e-02	9.84e-03	61
hsa04666110	Esophagus	ESCC	Fc gamma R-mediated phagocytosis	63/4205	97/8465	1.63e-03	4.89e-03	2.50e-03	63
hsa0060012	Esophagus	ESCC	Sphingolipid metabolism	36/4205	53/8465	5.41e-03	1.36e-02	6.99e-03	36
hsa0523114	Esophagus	ESCC	Choline metabolism in cancer	61/4205	98/8465	7.97e-03	1.92e-02	9.84e-03	61

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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

PLPP2

SNV

Missense_Mutation

c.437N>T

p.Pro146Leu

p.P146L

O43688

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-B6-A0RS-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PLPP2

SNV

Missense_Mutation

rs756459626

c.451N>A

p.Val151Ile

p.V151I

O43688

protein_coding

deleterious(0.05)

benign(0.083)

TCGA-BH-A0HA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PLPP2

insertion

In_Frame_Ins

novel

c.488_489insTTTCTTCCCTTGGAGGAGACGTGC

p.Val163_Tyr164insPhePheProTrpArgArgArgAla

p.V163_Y164insFFPWRRRA

O43688

protein_coding

TCGA-A8-A09X-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

PLPP2

SNV

Missense_Mutation

novel

c.884N>A

p.Gly295Asp

p.G295D

O43688

protein_coding

tolerated(0.07)

benign(0.242)

TCGA-VS-A9UJ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

PLPP2

insertion

Frame_Shift_Ins

novel

c.343_344insTAATTCCCCGTCAGCCCCATAG

p.Ala115ValfsTer70

p.A115Vfs*70

O43688

protein_coding

TCGA-C5-A1ML-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

PLPP2

SNV

Missense_Mutation

novel

c.283G>A

p.Ala95Thr

p.A95T

O43688

protein_coding

tolerated(0.26)

probably_damaging(0.981)

TCGA-AA-A022-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

PLPP2

SNV

Missense_Mutation

rs753966441

c.616N>A

p.Ala206Thr

p.A206T

O43688

protein_coding

deleterious(0.02)

benign(0.135)

TCGA-AU-6004-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

PLPP2

SNV

Missense_Mutation

c.760N>A

p.Ala254Thr

p.A254T

O43688

protein_coding

deleterious(0.04)

probably_damaging(0.983)

TCGA-G5-6233-01

Colorectum

rectum adenocarcinoma

Male

>=65

III/IV

Chemotherapy

5-fluorouracil

PLPP2

SNV

Missense_Mutation

novel

c.883N>T

p.Gly295Cys

p.G295C

O43688

protein_coding

deleterious(0)

possibly_damaging(0.855)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

PLPP2

SNV

Missense_Mutation

novel

c.814C>T

p.Pro272Ser

p.P272S

O43688

protein_coding

deleterious(0.04)

probably_damaging(0.929)

TCGA-AP-A1DK-01

Endometrium

uterine corpus endometrioid carcinoma

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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