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: LONP2

Gene summary for LONP2

Gene summary.

Gene information	Species	Human
	Gene symbol	LONP2
	Gene ID	83752
	Gene name	lon peptidase 2, peroxisomal
	Gene Alias	LONP
	Cytomap	16q12.1
	Gene Type	protein-coding
	GO ID	GO:0006082
	UniProtAcc	Q86WA8

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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
83752	LONP2	GSM4909289	Human	Breast	IDC	3.07e-02	5.74e-01	0.1064
83752	LONP2	GSM4909297	Human	Breast	IDC	2.81e-02	1.08e-01	0.1517
83752	LONP2	GSM4909304	Human	Breast	IDC	8.33e-04	2.99e-01	0.1636
83752	LONP2	GSM4909311	Human	Breast	IDC	5.60e-11	-1.18e-01	0.1534
83752	LONP2	GSM4909312	Human	Breast	IDC	8.60e-04	1.11e-01	0.1552
83752	LONP2	GSM4909319	Human	Breast	IDC	3.24e-12	-1.63e-01	0.1563
83752	LONP2	GSM4909321	Human	Breast	IDC	1.00e-04	-4.28e-02	0.1559
83752	LONP2	NCCBC6	Human	Breast	DCIS	2.58e-03	6.34e-01	0.2095
83752	LONP2	P1	Human	Breast	IDC	2.62e-04	5.55e-02	0.1527
83752	LONP2	DCIS2	Human	Breast	DCIS	5.18e-54	3.37e-01	0.0085
83752	LONP2	HTA11_3410_2000001011	Human	Colorectum	AD	5.13e-16	-4.92e-01	0.0155
83752	LONP2	HTA11_7862_2000001011	Human	Colorectum	AD	6.64e-03	-3.55e-01	-0.0179
83752	LONP2	HTA11_99999974143_84620	Human	Colorectum	MSS	1.28e-08	-4.74e-01	0.3005
83752	LONP2	A001-C-207	Human	Colorectum	FAP	3.23e-05	-3.17e-01	0.1278
83752	LONP2	A015-C-203	Human	Colorectum	FAP	2.37e-28	-5.37e-01	-0.1294
83752	LONP2	A015-C-204	Human	Colorectum	FAP	6.10e-10	-4.14e-01	-0.0228
83752	LONP2	A014-C-040	Human	Colorectum	FAP	3.28e-03	-2.58e-01	-0.1184
83752	LONP2	A002-C-201	Human	Colorectum	FAP	2.21e-17	-4.41e-01	0.0324
83752	LONP2	A002-C-203	Human	Colorectum	FAP	1.09e-02	-2.09e-01	0.2786
83752	LONP2	A001-C-119	Human	Colorectum	FAP	1.47e-07	-4.02e-01	-0.1557

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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
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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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:001921612	Breast	IDC	regulation of lipid metabolic process	45/1434	331/18723	1.21e-04	2.24e-03	45
GO:000660514	Breast	IDC	protein targeting	43/1434	314/18723	1.44e-04	2.53e-03	43
GO:007259413	Breast	IDC	establishment of protein localization to organelle	51/1434	422/18723	7.94e-04	9.55e-03	51
GO:007180612	Breast	IDC	protein transmembrane transport	12/1434	59/18723	1.49e-03	1.50e-02	12
GO:005160413	Breast	IDC	protein maturation	35/1434	294/18723	6.18e-03	4.40e-02	35
GO:000660523	Breast	DCIS	protein targeting	43/1390	314/18723	7.17e-05	1.41e-03	43
GO:001921621	Breast	DCIS	regulation of lipid metabolic process	43/1390	331/18723	2.37e-04	3.71e-03	43
GO:007259423	Breast	DCIS	establishment of protein localization to organelle	51/1390	422/18723	3.91e-04	5.40e-03	51
GO:007180621	Breast	DCIS	protein transmembrane transport	12/1390	59/18723	1.14e-03	1.22e-02	12
GO:006201213	Breast	DCIS	regulation of small molecule metabolic process	38/1390	334/18723	5.69e-03	4.10e-02	38
GO:005160422	Breast	DCIS	protein maturation	34/1390	294/18723	6.72e-03	4.66e-02	34
GO:0072594	Colorectum	AD	establishment of protein localization to organelle	148/3918	422/18723	7.95e-12	1.04e-09	148
GO:0006605	Colorectum	AD	protein targeting	105/3918	314/18723	1.39e-07	6.44e-06	105
GO:0044282	Colorectum	AD	small molecule catabolic process	118/3918	376/18723	1.05e-06	3.55e-05	118
GO:0006635	Colorectum	AD	fatty acid beta-oxidation	33/3918	74/18723	3.98e-06	1.09e-04	33
GO:0009062	Colorectum	AD	fatty acid catabolic process	41/3918	100/18723	4.02e-06	1.09e-04	41
GO:0019395	Colorectum	AD	fatty acid oxidation	40/3918	103/18723	2.43e-05	4.69e-04	40
GO:0016042	Colorectum	AD	lipid catabolic process	97/3918	320/18723	4.31e-05	7.56e-04	97
GO:0006631	Colorectum	AD	fatty acid metabolic process	114/3918	390/18723	5.58e-05	9.44e-04	114
GO:0017038	Colorectum	AD	protein import	67/3918	206/18723	6.34e-05	1.05e-03	67

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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

LONP2

SNV

Missense_Mutation

novel

c.709G>C

p.Asp237His

p.D237H

Q86WA8

protein_coding

tolerated(0.08)

possibly_damaging(0.459)

TCGA-3C-AALI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Poly E

Complete Response

LONP2

SNV

Missense_Mutation

novel

c.1205N>T

p.Gly402Val

p.G402V

Q86WA8

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

LONP2

SNV

Missense_Mutation

c.1043N>T

p.Lys348Ile

p.K348I

Q86WA8

protein_coding

deleterious(0)

possibly_damaging(0.581)

TCGA-A8-A090-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

LONP2

SNV

Missense_Mutation

c.787N>A

p.Glu263Lys

p.E263K

Q86WA8

protein_coding

tolerated(0.25)

benign(0.036)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

LONP2

SNV

Missense_Mutation

novel

c.346N>C

p.Glu116Gln

p.E116Q

Q86WA8

protein_coding

tolerated(0.13)

benign(0.051)

TCGA-AC-A5XS-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

femara

LONP2

SNV

Missense_Mutation

c.872N>G

p.Val291Gly

p.V291G

Q86WA8

protein_coding

tolerated(0.35)

benign(0.031)

TCGA-B6-A0I8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

LONP2

SNV

Missense_Mutation

c.1087N>G

p.Lys363Glu

p.K363E

Q86WA8

protein_coding

deleterious(0)

probably_damaging(0.931)

TCGA-E9-A1ND-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

aromasin

LONP2

SNV

Missense_Mutation

novel

c.1705G>A

p.Gly569Arg

p.G569R

Q86WA8

protein_coding

deleterious(0)

probably_damaging(0.96)

TCGA-E9-A3X8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphane

LONP2

insertion

Nonsense_Mutation

novel

c.466_467insGGTAG

p.Gln156ArgfsTer2

p.Q156Rfs*2

Q86WA8

protein_coding

TCGA-A7-A26I-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

LONP2

insertion

Nonsense_Mutation

novel

c.2107_2108insTAACTTCTATTGGATAGGAAATTTTGAAGCTCAAA

p.Trp703LeufsTer6

p.W703Lfs*6

Q86WA8

protein_coding

TCGA-A8-A079-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

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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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