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: LRRC59

Gene summary for LRRC59

Gene summary.

Gene information	Species	Human
	Gene symbol	LRRC59
	Gene ID	55379
	Gene name	leucine rich repeat containing 59
	Gene Alias	PRO1855
	Cytomap	17q21.33
	Gene Type	protein-coding
	GO ID	GO:0007154
	UniProtAcc	Q96AG4

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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
55379	LRRC59	GSM4909282	Human	Breast	IDC	1.11e-16	-2.98e-01	-0.0288
55379	LRRC59	GSM4909290	Human	Breast	IDC	5.08e-05	3.72e-01	0.2096
55379	LRRC59	GSM4909291	Human	Breast	IDC	8.06e-41	9.53e-01	0.1753
55379	LRRC59	GSM4909294	Human	Breast	IDC	2.09e-02	-1.88e-01	0.2022
55379	LRRC59	GSM4909296	Human	Breast	IDC	4.89e-10	-2.35e-01	0.1524
55379	LRRC59	GSM4909297	Human	Breast	IDC	3.91e-08	-1.72e-01	0.1517
55379	LRRC59	GSM4909301	Human	Breast	IDC	3.33e-02	-1.75e-01	0.1577
55379	LRRC59	GSM4909311	Human	Breast	IDC	3.27e-17	-2.08e-01	0.1534
55379	LRRC59	GSM4909312	Human	Breast	IDC	1.68e-05	1.14e-02	0.1552
55379	LRRC59	GSM4909319	Human	Breast	IDC	4.90e-23	-2.03e-01	0.1563
55379	LRRC59	GSM4909320	Human	Breast	IDC	2.12e-02	-1.82e-01	0.1575
55379	LRRC59	GSM4909321	Human	Breast	IDC	5.81e-09	-1.74e-01	0.1559
55379	LRRC59	brca1	Human	Breast	Precancer	3.54e-18	5.81e-01	-0.0338
55379	LRRC59	brca2	Human	Breast	Precancer	2.04e-08	3.58e-01	-0.024
55379	LRRC59	brca3	Human	Breast	Precancer	4.89e-07	2.89e-01	-0.0263
55379	LRRC59	M2	Human	Breast	IDC	3.65e-03	2.56e-01	0.21
55379	LRRC59	NCCBC14	Human	Breast	DCIS	6.27e-04	1.61e-01	0.2021
55379	LRRC59	NCCBC3	Human	Breast	DCIS	1.66e-02	-8.19e-02	0.1198
55379	LRRC59	P1	Human	Breast	IDC	9.22e-11	5.19e-02	0.1527
55379	LRRC59	P2	Human	Breast	IDC	4.79e-16	6.68e-01	0.21

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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
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
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:000726510	Esophagus	ESCC	Ras protein signal transduction	201/8552	337/18723	1.44e-07	2.30e-06	201
GO:00465789	Esophagus	ESCC	regulation of Ras protein signal transduction	106/8552	189/18723	2.49e-03	1.08e-02	106
GO:005105610	Esophagus	ESCC	regulation of small GTPase mediated signal transduction	157/8552	302/18723	1.55e-02	4.98e-02	157
GO:000726511	Liver	Cirrhotic	Ras protein signal transduction	119/4634	337/18723	8.16e-06	1.22e-04	119
GO:000726521	Liver	HCC	Ras protein signal transduction	187/7958	337/18723	8.89e-07	1.35e-05	187
GO:004657811	Liver	HCC	regulation of Ras protein signal transduction	100/7958	189/18723	2.42e-03	1.18e-02	100
GO:00072659	Oral cavity	OSCC	Ras protein signal transduction	185/7305	337/18723	1.95e-09	4.60e-08	185
GO:00465788	Oral cavity	OSCC	regulation of Ras protein signal transduction	90/7305	189/18723	9.58e-03	3.40e-02	90
GO:000726515	Oral cavity	LP	Ras protein signal transduction	109/4623	337/18723	8.44e-04	7.36e-03	109
GO:00072658	Prostate	BPH	Ras protein signal transduction	101/3107	337/18723	5.64e-10	2.79e-08	101
GO:00510568	Prostate	BPH	regulation of small GTPase mediated signal transduction	78/3107	302/18723	2.69e-05	3.16e-04	78
GO:00465787	Prostate	BPH	regulation of Ras protein signal transduction	53/3107	189/18723	5.08e-05	5.24e-04	53
GO:0051057	Prostate	BPH	positive regulation of small GTPase mediated signal transduction	20/3107	72/18723	1.16e-02	4.70e-02	20
GO:000726514	Prostate	Tumor	Ras protein signal transduction	101/3246	337/18723	6.29e-09	2.44e-07	101
GO:005105613	Prostate	Tumor	regulation of small GTPase mediated signal transduction	80/3246	302/18723	3.96e-05	4.57e-04	80
GO:004657814	Prostate	Tumor	regulation of Ras protein signal transduction	53/3246	189/18723	1.63e-04	1.46e-03	53
GO:000726523	Skin	cSCC	Ras protein signal transduction	132/4864	337/18723	6.17e-08	1.57e-06	132
GO:000726519	Thyroid	PTC	Ras protein signal transduction	162/5968	337/18723	3.16e-10	1.02e-08	162
GO:005105617	Thyroid	PTC	regulation of small GTPase mediated signal transduction	132/5968	302/18723	9.26e-06	1.04e-04	132
GO:004657817	Thyroid	PTC	regulation of Ras protein signal transduction	88/5968	189/18723	1.62e-05	1.70e-04	88

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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

LRRC59

SNV

Missense_Mutation

c.402N>C

p.Glu134Asp

p.E134D

Q96AG4

protein_coding

tolerated(0.16)

benign(0.133)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

LRRC59

insertion

Frame_Shift_Ins

novel

c.380_381insT

p.Ala128GlyfsTer3

p.A128Gfs*3

Q96AG4

protein_coding

TCGA-A2-A0EU-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

LRRC59

insertion

In_Frame_Ins

novel

c.378_379insCAGCATGCAAGACAACTATTGTCTGTG

p.Lys126_Val127insGlnHisAlaArgGlnLeuLeuSerVal

p.K126_V127insQHARQLLSV

Q96AG4

protein_coding

TCGA-A2-A0EU-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

LRRC59

SNV

Missense_Mutation

rs139115894

c.482N>A

p.Arg161Gln

p.R161Q

Q96AG4

protein_coding

tolerated(0.18)

benign(0.03)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

LRRC59

SNV

Missense_Mutation

novel

c.361N>C

p.Asp121His

p.D121H

Q96AG4

protein_coding

deleterious(0)

possibly_damaging(0.79)

TCGA-C5-A1MP-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

LRRC59

insertion

In_Frame_Ins

novel

c.437_438insCCTGCAATCCCA

p.Leu145_Gln146insHisLeuGlnSer

p.L145_Q146insHLQS

Q96AG4

protein_coding

TCGA-DS-A1OD-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

LRRC59

SNV

Missense_Mutation

c.443N>C

p.Met148Thr

p.M148T

Q96AG4

protein_coding

deleterious(0)

possibly_damaging(0.637)

TCGA-AA-3815-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

LRRC59

SNV

Missense_Mutation

rs200977500

c.451G>A

p.Val151Met

p.V151M

Q96AG4

protein_coding

tolerated(0.11)

benign(0.007)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

LRRC59

SNV

Missense_Mutation

rs143077743

c.481N>T

p.Arg161Trp

p.R161W

Q96AG4

protein_coding

deleterious(0)

probably_damaging(0.93)

TCGA-CM-6674-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

LRRC59

SNV

Missense_Mutation

c.629N>G

p.Lys210Arg

p.K210R

Q96AG4

protein_coding

tolerated(0.21)

possibly_damaging(0.531)

TCGA-AF-2693-01

Colorectum

rectum adenocarcinoma

Male

>=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
55379	LRRC59	NA		MELAGATRAN	MELAGATRAN	22494098

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