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: LIMS1

Gene summary for LIMS1

Gene summary.

Gene information	Species	Human
	Gene symbol	LIMS1
	Gene ID	3987
	Gene name	LIM zinc finger domain containing 1
	Gene Alias	PINCH
	Cytomap	2q12.3
	Gene Type	protein-coding
	GO ID	GO:0000902
	UniProtAcc	P48059

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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
3987	LIMS1	AEH-subject3	Human	Endometrium	AEH	4.82e-02	-1.98e-01	-0.2576
3987	LIMS1	EEC-subject1	Human	Endometrium	EEC	4.71e-03	6.95e-02	-0.2682
3987	LIMS1	EEC-subject2	Human	Endometrium	EEC	6.57e-06	-3.53e-01	-0.2607
3987	LIMS1	EEC-subject3	Human	Endometrium	EEC	2.48e-22	-3.67e-01	-0.2525
3987	LIMS1	GSM6177620_NYU_UCEC1_lib1_lib1	Human	Endometrium	EEC	6.90e-22	-5.55e-01	-0.1869
3987	LIMS1	GSM6177620_NYU_UCEC1_lib2_lib2	Human	Endometrium	EEC	1.99e-26	-6.42e-01	-0.1875
3987	LIMS1	GSM6177620_NYU_UCEC1_lib3_lib3	Human	Endometrium	EEC	1.07e-21	-5.25e-01	-0.1883
3987	LIMS1	GSM6177621_NYU_UCEC2_lib1_lib1	Human	Endometrium	EEC	5.38e-27	-4.57e-01	-0.1934
3987	LIMS1	GSM6177622_NYU_UCEC3_lib1_lib1	Human	Endometrium	EEC	5.53e-50	-6.98e-01	-0.1917
3987	LIMS1	GSM6177622_NYU_UCEC3_lib2_lib2	Human	Endometrium	EEC	1.17e-43	-7.64e-01	-0.1916
3987	LIMS1	GSM6177623_NYU_UCEC3_Vis	Human	Endometrium	EEC	8.90e-16	-4.93e-01	-0.1269
3987	LIMS1	LZE2D	Human	Esophagus	HGIN	2.29e-03	4.43e-01	0.0642
3987	LIMS1	LZE2T	Human	Esophagus	ESCC	1.66e-05	9.74e-01	0.082
3987	LIMS1	LZE3D	Human	Esophagus	HGIN	1.12e-05	8.33e-01	0.0668
3987	LIMS1	LZE4T	Human	Esophagus	ESCC	9.91e-45	1.51e+00	0.0811
3987	LIMS1	LZE7T	Human	Esophagus	ESCC	4.63e-13	7.30e-01	0.0667
3987	LIMS1	LZE8T	Human	Esophagus	ESCC	5.57e-14	4.05e-01	0.067
3987	LIMS1	LZE20T	Human	Esophagus	ESCC	2.61e-04	1.89e-01	0.0662
3987	LIMS1	LZE22D1	Human	Esophagus	HGIN	4.17e-02	7.00e-02	0.0595
3987	LIMS1	LZE22T	Human	Esophagus	ESCC	1.43e-02	2.96e-01	0.068

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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:001081015	Endometrium	AEH	regulation of cell-substrate adhesion	64/2100	221/18723	3.85e-13	9.62e-11	64
GO:002260415	Endometrium	AEH	regulation of cell morphogenesis	79/2100	309/18723	1.04e-12	2.24e-10	79
GO:00315899	Endometrium	AEH	cell-substrate adhesion	87/2100	363/18723	3.51e-12	5.70e-10	87
GO:190002410	Endometrium	AEH	regulation of substrate adhesion-dependent cell spreading	27/2100	57/18723	9.07e-12	1.43e-09	27
GO:004578516	Endometrium	AEH	positive regulation of cell adhesion	96/2100	437/18723	5.50e-11	7.18e-09	96
GO:190002610	Endometrium	AEH	positive regulation of substrate adhesion-dependent cell spreading	20/2100	41/18723	2.36e-09	1.89e-07	20
GO:001081116	Endometrium	AEH	positive regulation of cell-substrate adhesion	38/2100	123/18723	3.08e-09	2.26e-07	38
GO:001076910	Endometrium	AEH	regulation of cell morphogenesis involved in differentiation	31/2100	96/18723	2.70e-08	1.56e-06	31
GO:00019529	Endometrium	AEH	regulation of cell-matrix adhesion	37/2100	128/18723	3.58e-08	1.99e-06	37
GO:003444610	Endometrium	AEH	substrate adhesion-dependent cell spreading	33/2100	108/18723	4.45e-08	2.43e-06	33
GO:015011610	Endometrium	AEH	regulation of cell-substrate junction organization	25/2100	71/18723	8.77e-08	4.42e-06	25
GO:015011510	Endometrium	AEH	cell-substrate junction organization	31/2100	101/18723	1.01e-07	4.99e-06	31
GO:00072296	Endometrium	AEH	integrin-mediated signaling pathway	32/2100	107/18723	1.24e-07	5.80e-06	32
GO:00480418	Endometrium	AEH	focal adhesion assembly	28/2100	87/18723	1.36e-07	6.14e-06	28
GO:00071609	Endometrium	AEH	cell-matrix adhesion	54/2100	233/18723	1.42e-07	6.37e-06	54
GO:00070449	Endometrium	AEH	cell-substrate junction assembly	29/2100	95/18723	2.93e-07	1.28e-05	29
GO:00518939	Endometrium	AEH	regulation of focal adhesion assembly	23/2100	66/18723	3.54e-07	1.51e-05	23
GO:00901099	Endometrium	AEH	regulation of cell-substrate junction assembly	23/2100	66/18723	3.54e-07	1.51e-05	23
GO:00107709	Endometrium	AEH	positive regulation of cell morphogenesis involved in differentiation	24/2100	79/18723	3.33e-06	9.03e-05	24
GO:00343299	Endometrium	AEH	cell junction assembly	78/2100	420/18723	4.80e-06	1.24e-04	78

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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

LIMS1

SNV

Missense_Mutation

novel

c.61N>T

p.Arg21Cys

p.R21C

P48059

protein_coding

deleterious_low_confidence(0.01)

benign(0.348)

TCGA-AC-A2FE-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

LIMS1

SNV

Missense_Mutation

novel

c.473N>T

p.Arg158Leu

p.R158L

P48059

protein_coding

tolerated(0.39)

benign(0.015)

TCGA-BH-A1FC-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

LIMS1

SNV

Missense_Mutation

c.1127G>T

p.Arg376Ile

p.R376I

P48059

protein_coding

tolerated(0.06)

probably_damaging(0.991)

TCGA-D8-A1X6-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

tamoxiphen

LIMS1

SNV

Missense_Mutation

rs149119038

c.67N>A

p.Asp23Asn

p.D23N

P48059

protein_coding

tolerated_low_confidence(0.48)

benign(0)

TCGA-EA-A3QE-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

LIMS1

SNV

Missense_Mutation

c.247N>A

p.Glu83Lys

p.E83K

P48059

protein_coding

deleterious(0)

probably_damaging(0.973)

TCGA-Q1-A73O-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

LIMS1

SNV

Missense_Mutation

c.874C>T

p.Arg292Cys

p.R292C

P48059

protein_coding

deleterious(0)

probably_damaging(0.982)

TCGA-AA-A00N-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

LIMS1

SNV

Missense_Mutation

rs200004487

c.220N>T

p.Arg74Cys

p.R74C

P48059

protein_coding

deleterious(0.02)

probably_damaging(0.953)

TCGA-D5-6930-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

LIMS1

insertion

Nonsense_Mutation

novel

c.892_893insTTTGAGACA

p.Gly298delinsValTerAspSer

p.G298delinsV*DS

P48059

protein_coding

TCGA-AM-5820-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

LIMS1

SNV

Missense_Mutation

novel

c.556N>T

p.Arg186Cys

p.R186C

P48059

protein_coding

deleterious(0.01)

possibly_damaging(0.901)

TCGA-AJ-A3EL-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

LIMS1

SNV

Missense_Mutation

rs377342624

c.794N>A

p.Arg265His

p.R265H

P48059

protein_coding

deleterious(0.04)

probably_damaging(0.918)

TCGA-AJ-A3OK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Chemotherapy

carboplatin

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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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