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	PTC05	Human	Thyroid	PTC	4.35e-19	4.13e-01	0.2065
4026	LPP	PTC06	Human	Thyroid	PTC	1.19e-15	3.99e-01	0.2057
4026	LPP	PTC07	Human	Thyroid	PTC	1.56e-10	1.52e-01	0.2044
4026	LPP	ATC08	Human	Thyroid	ATC	4.61e-04	5.27e-02	0.0541
4026	LPP	ATC09	Human	Thyroid	ATC	5.36e-08	2.89e-01	0.2871
4026	LPP	ATC11	Human	Thyroid	ATC	4.34e-11	1.53e+00	0.3386
4026	LPP	ATC12	Human	Thyroid	ATC	1.34e-24	5.17e-01	0.34
4026	LPP	ATC13	Human	Thyroid	ATC	1.34e-42	8.36e-01	0.34
4026	LPP	ATC1	Human	Thyroid	ATC	3.67e-09	3.70e-01	0.2878
4026	LPP	ATC2	Human	Thyroid	ATC	1.30e-23	2.71e+00	0.34
4026	LPP	ATC3	Human	Thyroid	ATC	4.19e-20	1.62e+00	0.338
4026	LPP	ATC4	Human	Thyroid	ATC	5.97e-32	6.85e-01	0.34
4026	LPP	ATC5	Human	Thyroid	ATC	5.73e-43	9.06e-01	0.34

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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:004854510	Cervix	CC	response to steroid hormone	74/2311	339/18723	5.71e-07	2.09e-05	74
GO:00310988	Cervix	CC	stress-activated protein kinase signaling cascade	58/2311	247/18723	8.02e-07	2.89e-05	58
GO:00305229	Cervix	CC	intracellular receptor signaling pathway	60/2311	265/18723	1.89e-06	5.97e-05	60
GO:00485118	Cervix	CC	rhythmic process	65/2311	298/18723	2.79e-06	8.04e-05	65
GO:00514038	Cervix	CC	stress-activated MAPK cascade	55/2311	239/18723	2.96e-06	8.31e-05	55
GO:00703027	Cervix	CC	regulation of stress-activated protein kinase signaling cascade	46/2311	195/18723	9.35e-06	2.11e-04	46
GO:00064708	Cervix	CC	protein dephosphorylation	60/2311	281/18723	1.33e-05	2.68e-04	60
GO:00328727	Cervix	CC	regulation of stress-activated MAPK cascade	44/2311	192/18723	3.09e-05	5.10e-04	44
GO:00076238	Cervix	CC	circadian rhythm	46/2311	210/18723	6.76e-05	9.60e-04	46
GO:00380664	Cervix	CC	p38MAPK cascade	17/2311	55/18723	2.25e-04	2.54e-03	17
GO:00518964	Cervix	CC	regulation of protein kinase B signaling	39/2311	185/18723	5.25e-04	5.10e-03	39
GO:00434913	Cervix	CC	protein kinase B signaling	43/2311	211/18723	5.95e-04	5.60e-03	43
GO:00072545	Cervix	CC	JNK cascade	35/2311	167/18723	1.10e-03	9.09e-03	35
GO:19007442	Cervix	CC	regulation of p38MAPK cascade	14/2311	47/18723	1.18e-03	9.56e-03	14
GO:00163117	Cervix	CC	dephosphorylation	73/2311	417/18723	1.23e-03	9.87e-03	73
GO:00713839	Cervix	CC	cellular response to steroid hormone stimulus	40/2311	204/18723	1.93e-03	1.42e-02	40
GO:00463285	Cervix	CC	regulation of JNK cascade	28/2311	133/18723	3.06e-03	2.01e-02	28
GO:00305188	Cervix	CC	intracellular steroid hormone receptor signaling pathway	25/2311	116/18723	3.59e-03	2.30e-02	25
GO:0002507	Cervix	CC	tolerance induction	9/2311	28/18723	5.02e-03	2.98e-02	9
GO:00305218	Cervix	CC	androgen receptor signaling pathway	12/2311	44/18723	5.76e-03	3.30e-02	12

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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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