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: LPP

Gene summary for LPP

Gene summary.

Gene information	Species	Human
	Gene symbol	LPP
	Gene ID	4026
	Gene name	LIM domain containing preferred translocation partner in lipoma
	Gene Alias	LPP
	Cytomap	3q27.3-q28
	Gene Type	protein-coding
	GO ID	GO:0007155
	UniProtAcc	B7ZLW0

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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
4026	LPP	GSM4909280	Human	Breast	Precancer	8.82e-03	-5.29e-01	0.0305
4026	LPP	GSM4909281	Human	Breast	IDC	5.56e-04	3.23e-01	0.21
4026	LPP	GSM4909286	Human	Breast	IDC	2.87e-03	-1.65e-01	0.1081
4026	LPP	GSM4909288	Human	Breast	IDC	3.65e-02	-3.77e-01	0.0988
4026	LPP	GSM4909293	Human	Breast	IDC	2.42e-03	1.77e-01	0.1581
4026	LPP	GSM4909294	Human	Breast	IDC	1.22e-08	-4.18e-01	0.2022
4026	LPP	GSM4909296	Human	Breast	IDC	1.61e-17	-3.87e-01	0.1524
4026	LPP	GSM4909297	Human	Breast	IDC	5.79e-25	-4.82e-01	0.1517
4026	LPP	GSM4909309	Human	Breast	IDC	4.51e-03	-2.60e-01	0.0483
4026	LPP	GSM4909311	Human	Breast	IDC	4.93e-31	-3.69e-01	0.1534
4026	LPP	GSM4909312	Human	Breast	IDC	1.11e-13	-2.85e-01	0.1552
4026	LPP	GSM4909319	Human	Breast	IDC	1.60e-34	-5.51e-01	0.1563
4026	LPP	GSM4909320	Human	Breast	IDC	2.06e-11	-4.76e-01	0.1575
4026	LPP	GSM4909321	Human	Breast	IDC	6.46e-24	-4.92e-01	0.1559
4026	LPP	brca1	Human	Breast	Precancer	7.42e-04	-3.01e-01	-0.0338
4026	LPP	M2	Human	Breast	IDC	4.60e-02	-2.11e-01	0.21
4026	LPP	NCCBC11	Human	Breast	DCIS	3.29e-02	-1.49e-01	0.1232
4026	LPP	NCCBC14	Human	Breast	DCIS	8.82e-12	-7.15e-02	0.2021
4026	LPP	NCCBC2	Human	Breast	DCIS	4.00e-03	-1.90e-01	0.1554
4026	LPP	NCCBC5	Human	Breast	DCIS	3.97e-19	-3.66e-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
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
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:003051831	Oral cavity	NEOLP	intracellular steroid hormone receptor signaling pathway	27/2005	116/18723	7.54e-05	9.71e-04	27
GO:002240923	Oral cavity	NEOLP	positive regulation of cell-cell adhesion	51/2005	284/18723	1.50e-04	1.72e-03	51
GO:005109031	Oral cavity	NEOLP	regulation of DNA-binding transcription factor activity	72/2005	440/18723	1.66e-04	1.84e-03	72
GO:004340131	Oral cavity	NEOLP	steroid hormone mediated signaling pathway	29/2005	136/18723	2.17e-04	2.29e-03	29
GO:001059514	Oral cavity	NEOLP	positive regulation of endothelial cell migration	28/2005	133/18723	3.44e-04	3.33e-03	28
GO:003052123	Oral cavity	NEOLP	androgen receptor signaling pathway	13/2005	44/18723	4.99e-04	4.42e-03	13
GO:005109121	Oral cavity	NEOLP	positive regulation of DNA-binding transcription factor activity	45/2005	260/18723	8.06e-04	6.39e-03	45
GO:003362713	Oral cavity	NEOLP	cell adhesion mediated by integrin	17/2005	72/18723	1.29e-03	9.43e-03	17
GO:001059414	Oral cavity	NEOLP	regulation of endothelial cell migration	40/2005	232/18723	1.64e-03	1.14e-02	40
GO:001631122	Oral cavity	NEOLP	dephosphorylation	64/2005	417/18723	1.98e-03	1.33e-02	64
GO:000975515	Oral cavity	NEOLP	hormone-mediated signaling pathway	33/2005	190/18723	3.53e-03	2.07e-02	33
GO:004854518	Prostate	BPH	response to steroid hormone	109/3107	339/18723	9.35e-13	8.15e-11	109
GO:004851110	Prostate	BPH	rhythmic process	96/3107	298/18723	1.88e-11	1.31e-09	96
GO:000762310	Prostate	BPH	circadian rhythm	73/3107	210/18723	1.02e-10	6.02e-09	73
GO:007138316	Prostate	BPH	cellular response to steroid hormone stimulus	71/3107	204/18723	1.72e-10	9.79e-09	71
GO:003052110	Prostate	BPH	androgen receptor signaling pathway	23/3107	44/18723	5.88e-08	1.57e-06	23
GO:003051810	Prostate	BPH	intracellular steroid hormone receptor signaling pathway	43/3107	116/18723	8.48e-08	2.12e-06	43
GO:003052216	Prostate	BPH	intracellular receptor signaling pathway	77/3107	265/18723	2.49e-07	5.42e-06	77
GO:000647010	Prostate	BPH	protein dephosphorylation	78/3107	281/18723	1.53e-06	2.63e-05	78
GO:004340110	Prostate	BPH	steroid hormone mediated signaling pathway	45/3107	136/18723	1.78e-06	2.98e-05	45

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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

LPP

SNV

Missense_Mutation

rs749505857

c.1396G>A

p.Glu466Lys

p.E466K

protein_coding

deleterious(0)

possibly_damaging(0.889)

TCGA-5L-AAT0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

LPP

SNV

Missense_Mutation

c.922N>C

p.Gly308Arg

p.G308R

protein_coding

tolerated(0.11)

possibly_damaging(0.818)

TCGA-A1-A0SH-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

LPP

SNV

Missense_Mutation

rs756003756

c.1457G>A

p.Arg486Gln

p.R486Q

protein_coding

deleterious(0)

possibly_damaging(0.74)

TCGA-A1-A0SM-01

Breast

breast invasive carcinoma

Male

>=65

I/II

Unknown

LPP

SNV

Missense_Mutation

c.254N>G

p.Ser85Cys

p.S85C

protein_coding

tolerated(0.05)

benign(0.276)

TCGA-A7-A26G-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

LPP

SNV

Missense_Mutation

c.1834N>G

p.Leu612Val

p.L612V

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.974)

TCGA-A8-A083-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

LPP

SNV

Missense_Mutation

novel

c.1576N>A

p.Glu526Lys

p.E526K

protein_coding

deleterious(0)

possibly_damaging(0.57)

TCGA-A8-A0A7-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

LPP

SNV

Missense_Mutation

novel

c.1274N>T

p.Gly425Val

p.G425V

protein_coding

deleterious(0)

possibly_damaging(0.874)

TCGA-AC-A2QH-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

LPP

SNV

Missense_Mutation

c.1391N>G

p.Tyr464Cys

p.Y464C

protein_coding

deleterious(0)

probably_damaging(0.95)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

LPP

SNV

Missense_Mutation

novel

c.452N>G

p.Ser151Cys

p.S151C

protein_coding

deleterious(0.02)

possibly_damaging(0.885)

TCGA-PE-A5DE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

LPP

SNV

Missense_Mutation

c.1751N>A

p.Cys584Tyr

p.C584Y

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

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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