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: LASP1

Gene summary for LASP1

Gene summary.

Gene information	Species	Human
	Gene symbol	LASP1
	Gene ID	3927
	Gene name	LIM and SH3 protein 1
	Gene Alias	Lasp-1
	Cytomap	17q12
	Gene Type	protein-coding
	GO ID	GO:0006810
	UniProtAcc	B4DIC4

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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
3927	LASP1	GSM4909290	Human	Breast	IDC	8.06e-58	1.18e+00	0.2096
3927	LASP1	GSM4909292	Human	Breast	IDC	1.97e-06	7.60e-01	0.1236
3927	LASP1	GSM4909293	Human	Breast	IDC	3.59e-13	4.28e-01	0.1581
3927	LASP1	GSM4909298	Human	Breast	IDC	1.86e-02	1.80e-03	0.1551
3927	LASP1	GSM4909311	Human	Breast	IDC	2.84e-06	-1.00e-01	0.1534
3927	LASP1	GSM4909313	Human	Breast	IDC	1.64e-02	2.64e-01	0.0391
3927	LASP1	GSM4909319	Human	Breast	IDC	6.33e-12	-1.75e-01	0.1563
3927	LASP1	GSM4909320	Human	Breast	IDC	3.41e-02	-1.87e-01	0.1575
3927	LASP1	NCCBC5	Human	Breast	DCIS	2.77e-09	4.12e-01	0.2046
3927	LASP1	P1	Human	Breast	IDC	4.43e-09	-6.48e-02	0.1527
3927	LASP1	DCIS2	Human	Breast	DCIS	1.54e-34	-8.79e-03	0.0085
3927	LASP1	LZE4T	Human	Esophagus	ESCC	2.16e-06	2.37e-01	0.0811
3927	LASP1	LZE7T	Human	Esophagus	ESCC	3.76e-02	2.08e-01	0.0667
3927	LASP1	LZE8T	Human	Esophagus	ESCC	1.62e-05	2.27e-01	0.067
3927	LASP1	LZE20T	Human	Esophagus	ESCC	7.87e-03	3.87e-02	0.0662
3927	LASP1	LZE24T	Human	Esophagus	ESCC	4.93e-35	1.20e+00	0.0596
3927	LASP1	LZE21T	Human	Esophagus	ESCC	4.71e-05	2.16e-01	0.0655
3927	LASP1	P1T-E	Human	Esophagus	ESCC	5.99e-12	5.60e-01	0.0875
3927	LASP1	P2T-E	Human	Esophagus	ESCC	1.32e-31	4.78e-01	0.1177
3927	LASP1	P4T-E	Human	Esophagus	ESCC	1.60e-16	4.15e-01	0.1323

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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
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
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:000716023	Oral cavity	NEOLP	cell-matrix adhesion	62/2005	233/18723	6.73e-12	1.14e-09	62
GO:015011624	Oral cavity	NEOLP	regulation of cell-substrate junction organization	30/2005	71/18723	7.44e-12	1.17e-09	30
GO:000701534	Oral cavity	NEOLP	actin filament organization	94/2005	442/18723	4.49e-11	5.80e-09	94
GO:000195223	Oral cavity	NEOLP	regulation of cell-matrix adhesion	41/2005	128/18723	5.14e-11	6.30e-09	41
GO:003297033	Oral cavity	NEOLP	regulation of actin filament-based process	85/2005	397/18723	2.70e-10	2.51e-08	85
GO:003432923	Oral cavity	NEOLP	cell junction assembly	88/2005	420/18723	4.18e-10	3.44e-08	88
GO:000166725	Oral cavity	NEOLP	ameboidal-type cell migration	96/2005	475/18723	5.16e-10	4.14e-08	96
GO:003133433	Oral cavity	NEOLP	positive regulation of protein-containing complex assembly	58/2005	237/18723	1.09e-09	7.92e-08	58
GO:001063123	Oral cavity	NEOLP	epithelial cell migration	77/2005	357/18723	1.32e-09	9.43e-08	77
GO:190290533	Oral cavity	NEOLP	positive regulation of supramolecular fiber organization	53/2005	209/18723	1.47e-09	1.01e-07	53
GO:003295633	Oral cavity	NEOLP	regulation of actin cytoskeleton organization	77/2005	358/18723	1.51e-09	1.02e-07	77
GO:003227133	Oral cavity	NEOLP	regulation of protein polymerization	57/2005	233/18723	1.54e-09	1.03e-07	57
GO:009013023	Oral cavity	NEOLP	tissue migration	78/2005	365/18723	1.61e-09	1.06e-07	78
GO:009013223	Oral cavity	NEOLP	epithelium migration	77/2005	360/18723	1.96e-09	1.24e-07	77
GO:005125833	Oral cavity	NEOLP	protein polymerization	67/2005	297/18723	2.27e-09	1.40e-07	67
GO:000716333	Oral cavity	NEOLP	establishment or maintenance of cell polarity	53/2005	218/18723	7.21e-09	3.82e-07	53
GO:002241131	Oral cavity	NEOLP	cellular component disassembly	87/2005	443/18723	1.39e-08	6.46e-07	87
GO:00301982	Oral cavity	NEOLP	extracellular matrix organization	64/2005	301/18723	5.66e-08	2.24e-06	64
GO:00430622	Oral cavity	NEOLP	extracellular structure organization	64/2005	302/18723	6.44e-08	2.50e-06	64
GO:00452292	Oral cavity	NEOLP	external encapsulating structure organization	64/2005	304/18723	8.33e-08	3.17e-06	64

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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

LASP1

SNV

Missense_Mutation

novel

c.108N>T

p.Lys36Asn

p.K36N

Q14847

protein_coding

tolerated(0.05)

benign(0.033)

TCGA-AN-A0FS-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

LASP1

SNV

Missense_Mutation

c.650N>C

p.Asp217Ala

p.D217A

Q14847

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-BH-A0DH-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

LASP1

SNV

Missense_Mutation

c.326N>A

p.Arg109Lys

p.R109K

Q14847

protein_coding

deleterious(0.01)

probably_damaging(0.964)

TCGA-BH-A18P-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

LASP1

insertion

In_Frame_Ins

novel

c.233_234insAATACTATTCCTATT

p.Ser78delinsArgIleLeuPheLeuPhe

p.S78delinsRILFLF

Q14847

protein_coding

TCGA-A2-A0D2-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

LASP1

insertion

In_Frame_Ins

novel

c.235_236insCAGATA

p.Glu79delinsAlaAspLys

p.E79delinsADK

Q14847

protein_coding

TCGA-A2-A0D2-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

LASP1

SNV

Missense_Mutation

c.90C>G

p.Phe30Leu

p.F30L

Q14847

protein_coding

deleterious(0)

benign(0.442)

TCGA-IR-A3LI-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

LASP1

SNV

Missense_Mutation

c.164C>T

p.Ala55Val

p.A55V

Q14847

protein_coding

tolerated(0.06)

benign(0.051)

TCGA-AA-3949-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

LASP1

SNV

Missense_Mutation

c.164N>T

p.Ala55Val

p.A55V

Q14847

protein_coding

tolerated(0.06)

benign(0.051)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

LASP1

SNV

Missense_Mutation

novel

c.64N>A

p.Asp22Asn

p.D22N

Q14847

protein_coding

deleterious(0)

possibly_damaging(0.866)

TCGA-A5-A2K5-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

LASP1

SNV

Missense_Mutation

c.616N>T

p.Arg206Trp

p.R206W

Q14847

protein_coding

deleterious(0.01)

probably_damaging(0.965)

TCGA-AP-A051-01

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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