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:01501166	Liver	NAFLD	regulation of cell-substrate junction organization	22/1882	71/18723	9.51e-07	4.92e-05	22
GO:00518936	Liver	NAFLD	regulation of focal adhesion assembly	21/1882	66/18723	1.03e-06	5.22e-05	21
GO:00901096	Liver	NAFLD	regulation of cell-substrate junction assembly	21/1882	66/18723	1.03e-06	5.22e-05	21
GO:00715593	Liver	NAFLD	response to transforming growth factor beta	51/1882	256/18723	1.43e-06	6.58e-05	51
GO:00315896	Liver	NAFLD	cell-substrate adhesion	65/1882	363/18723	2.84e-06	1.18e-04	65
GO:00430875	Liver	NAFLD	regulation of GTPase activity	62/1882	348/18723	5.65e-06	2.03e-04	62
GO:00019526	Liver	NAFLD	regulation of cell-matrix adhesion	30/1882	128/18723	7.84e-06	2.63e-04	30
GO:00715603	Liver	NAFLD	cellular response to transforming growth factor beta stimulus	48/1882	250/18723	8.27e-06	2.76e-04	48
GO:00107697	Liver	NAFLD	regulation of cell morphogenesis involved in differentiation	24/1882	96/18723	1.98e-05	5.62e-04	24
GO:19000247	Liver	NAFLD	regulation of substrate adhesion-dependent cell spreading	17/1882	57/18723	2.81e-05	7.46e-04	17
GO:0051894	Liver	NAFLD	positive regulation of focal adhesion assembly	11/1882	28/18723	4.36e-05	1.06e-03	11
GO:0150117	Liver	NAFLD	positive regulation of cell-substrate junction organization	12/1882	33/18723	4.85e-05	1.15e-03	12
GO:00344467	Liver	NAFLD	substrate adhesion-dependent cell spreading	25/1882	108/18723	5.41e-05	1.23e-03	25
GO:00435474	Liver	NAFLD	positive regulation of GTPase activity	45/1882	255/18723	1.30e-04	2.47e-03	45
GO:00343296	Liver	NAFLD	cell junction assembly	66/1882	420/18723	1.64e-04	3.00e-03	66
GO:00107707	Liver	NAFLD	positive regulation of cell morphogenesis involved in differentiation	19/1882	79/18723	2.42e-04	4.06e-03	19
GO:00108117	Liver	NAFLD	positive regulation of cell-substrate adhesion	25/1882	123/18723	4.73e-04	6.74e-03	25
GO:19000267	Liver	NAFLD	positive regulation of substrate adhesion-dependent cell spreading	12/1882	41/18723	5.05e-04	7.15e-03	12
GO:19018884	Liver	NAFLD	regulation of cell junction assembly	36/1882	204/18723	5.82e-04	7.77e-03	36
GO:00075687	Liver	NAFLD	aging	53/1882	339/18723	7.78e-04	9.77e-03	53

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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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