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: PLP2

Gene summary for PLP2

Gene summary.

Gene information	Species	Human
	Gene symbol	PLP2
	Gene ID	5355
	Gene name	proteolipid protein 2
	Gene Alias	A4
	Cytomap	Xp11.23
	Gene Type	protein-coding
	GO ID	GO:0006810
	UniProtAcc	A0A024QYW3

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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
5355	PLP2	GSM4909282	Human	Breast	IDC	2.65e-03	3.11e-01	-0.0288
5355	PLP2	GSM4909285	Human	Breast	IDC	5.85e-06	2.51e-01	0.21
5355	PLP2	GSM4909286	Human	Breast	IDC	1.52e-02	-1.96e-01	0.1081
5355	PLP2	GSM4909293	Human	Breast	IDC	4.96e-02	-2.27e-01	0.1581
5355	PLP2	GSM4909294	Human	Breast	IDC	3.60e-08	-3.36e-01	0.2022
5355	PLP2	GSM4909296	Human	Breast	IDC	7.18e-06	1.51e-01	0.1524
5355	PLP2	GSM4909297	Human	Breast	IDC	1.24e-06	1.05e-01	0.1517
5355	PLP2	GSM4909298	Human	Breast	IDC	5.56e-03	-2.95e-01	0.1551
5355	PLP2	GSM4909304	Human	Breast	IDC	8.63e-03	2.95e-01	0.1636
5355	PLP2	GSM4909311	Human	Breast	IDC	4.06e-19	-2.21e-01	0.1534
5355	PLP2	GSM4909312	Human	Breast	IDC	6.74e-04	-2.46e-02	0.1552
5355	PLP2	GSM4909319	Human	Breast	IDC	2.45e-31	-2.00e-02	0.1563
5355	PLP2	GSM4909320	Human	Breast	IDC	8.02e-03	1.09e-01	0.1575
5355	PLP2	GSM4909321	Human	Breast	IDC	1.44e-06	2.44e-02	0.1559
5355	PLP2	brca1	Human	Breast	Precancer	8.87e-24	6.75e-01	-0.0338
5355	PLP2	brca2	Human	Breast	Precancer	9.26e-13	4.12e-01	-0.024
5355	PLP2	brca3	Human	Breast	Precancer	7.68e-12	4.22e-01	-0.0263
5355	PLP2	brca10	Human	Breast	Precancer	5.90e-04	3.66e-01	-0.0029
5355	PLP2	NCCBC14	Human	Breast	DCIS	4.84e-10	-2.16e-01	0.2021
5355	PLP2	NCCBC5	Human	Breast	DCIS	3.30e-09	-1.46e-01	0.2046

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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
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
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
GO:00021819	Breast	Precancer	cytoplasmic translation	80/1080	148/18723	1.59e-59	8.54e-56	80
GO:00064147	Breast	Precancer	translational elongation	10/1080	55/18723	1.06e-03	1.18e-02	10
GO:000218114	Breast	IDC	cytoplasmic translation	82/1434	148/18723	2.60e-52	1.48e-48	82
GO:000218124	Breast	DCIS	cytoplasmic translation	82/1390	148/18723	2.21e-53	1.25e-49	82
GO:000641413	Breast	DCIS	translational elongation	10/1390	55/18723	6.66e-03	4.62e-02	10
GO:000218110	Cervix	CC	cytoplasmic translation	96/2311	148/18723	4.87e-51	2.91e-47	96
GO:00192213	Cervix	CC	cytokine-mediated signaling pathway	84/2311	472/18723	3.25e-04	3.44e-03	84
GO:000218115	Cervix	HSIL_HPV	cytoplasmic translation	86/737	148/18723	3.97e-82	1.91e-78	86
GO:00064148	Cervix	HSIL_HPV	translational elongation	7/737	55/18723	5.59e-03	4.47e-02	7
GO:001922121	Cervix	N_HPV	cytokine-mediated signaling pathway	36/534	472/18723	9.30e-08	9.21e-06	36
GO:0002181	Colorectum	AD	cytoplasmic translation	109/3918	148/18723	3.40e-43	2.13e-39	109
GO:0052547	Colorectum	AD	regulation of peptidase activity	137/3918	461/18723	4.12e-06	1.12e-04	137
GO:0045861	Colorectum	AD	negative regulation of proteolysis	106/3918	351/18723	2.33e-05	4.57e-04	106
GO:0052548	Colorectum	AD	regulation of endopeptidase activity	124/3918	432/18723	6.58e-05	1.07e-03	124
GO:0006414	Colorectum	AD	translational elongation	21/3918	55/18723	2.53e-03	1.93e-02	21
GO:00021811	Colorectum	SER	cytoplasmic translation	102/2897	148/18723	1.38e-48	8.49e-45	102
GO:00525471	Colorectum	SER	regulation of peptidase activity	114/2897	461/18723	1.18e-07	7.17e-06	114
GO:00458611	Colorectum	SER	negative regulation of proteolysis	88/2897	351/18723	1.74e-06	7.50e-05	88
GO:00525481	Colorectum	SER	regulation of endopeptidase activity	103/2897	432/18723	2.86e-06	1.16e-04	103
GO:0051346	Colorectum	SER	negative regulation of hydrolase activity	82/2897	379/18723	8.19e-04	1.01e-02	82

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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

PLP2

SNV

Missense_Mutation

rs782265454

c.406C>T

p.Arg136Trp

p.R136W

Q04941

protein_coding

deleterious(0.02)

possibly_damaging(0.446)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PLP2

SNV

Missense_Mutation

novel

c.407N>A

p.Arg136Gln

p.R136Q

Q04941

protein_coding

tolerated(0.33)

benign(0.01)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PLP2

insertion

Nonsense_Mutation

novel

c.361_362insATTGAGATGATC

p.Ala121delinsAspTerAspAspPro

p.A121delinsD*DDP

Q04941

protein_coding

TCGA-A2-A0T2-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

xeloda

PLP2

insertion

Frame_Shift_Ins

novel

c.291_292insG

p.Thr98AspfsTer8

p.T98Dfs*8

Q04941

protein_coding

TCGA-A8-A09E-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozole

PLP2

insertion

Frame_Shift_Ins

novel

c.292_293insTCCACCCGCCTCGG

p.Thr98IlefsTer27

p.T98Ifs*27

Q04941

protein_coding

TCGA-A8-A09E-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozole

PLP2

SNV

Missense_Mutation

rs782265454

c.406N>T

p.Arg136Trp

p.R136W

Q04941

protein_coding

deleterious(0.02)

possibly_damaging(0.446)

TCGA-Q1-A73O-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

PLP2

SNV

Missense_Mutation

rs782368813

c.212T>C

p.Leu71Pro

p.L71P

Q04941

protein_coding

deleterious(0)

probably_damaging(0.993)

TCGA-AA-3815-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

PLP2

SNV

Missense_Mutation

c.130N>A

p.Ala44Thr

p.A44T

Q04941

protein_coding

tolerated(0.1)

benign(0.011)

TCGA-AZ-6601-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

PLP2

SNV

Missense_Mutation

c.107N>C

p.Leu36Pro

p.L36P

Q04941

protein_coding

deleterious(0)

benign(0.362)

TCGA-CK-4951-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

PLP2

SNV

Missense_Mutation

novel

c.315N>T

p.Glu105Asp

p.E105D

Q04941

protein_coding

tolerated(0.46)

benign(0.005)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

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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