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: LOXL2

Gene summary for LOXL2

Gene summary.

Gene information	Species	Human
	Gene symbol	LOXL2
	Gene ID	4017
	Gene name	lysyl oxidase like 2
	Gene Alias	LOR
	Cytomap	8p21.3
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	Q9Y4K0

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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
4017	LOXL2	LZE6T	Human	Esophagus	ESCC	2.05e-03	3.77e-01	0.0845
4017	LOXL2	P4T-E	Human	Esophagus	ESCC	2.17e-05	3.16e-01	0.1323
4017	LOXL2	P5T-E	Human	Esophagus	ESCC	1.41e-02	1.75e-01	0.1327
4017	LOXL2	P9T-E	Human	Esophagus	ESCC	1.81e-05	2.47e-01	0.1131
4017	LOXL2	P11T-E	Human	Esophagus	ESCC	1.65e-09	6.02e-01	0.1426
4017	LOXL2	P17T-E	Human	Esophagus	ESCC	3.85e-07	8.68e-01	0.1278
4017	LOXL2	P19T-E	Human	Esophagus	ESCC	3.32e-07	8.93e-01	0.1662
4017	LOXL2	P23T-E	Human	Esophagus	ESCC	6.11e-03	3.56e-01	0.108
4017	LOXL2	P24T-E	Human	Esophagus	ESCC	9.38e-18	5.74e-01	0.1287
4017	LOXL2	P32T-E	Human	Esophagus	ESCC	8.62e-43	1.14e+00	0.1666
4017	LOXL2	P36T-E	Human	Esophagus	ESCC	5.53e-03	3.05e-01	0.1187
4017	LOXL2	P37T-E	Human	Esophagus	ESCC	4.92e-55	1.41e+00	0.1371
4017	LOXL2	P42T-E	Human	Esophagus	ESCC	3.77e-09	6.43e-01	0.1175
4017	LOXL2	P44T-E	Human	Esophagus	ESCC	1.72e-10	8.67e-01	0.1096
4017	LOXL2	P47T-E	Human	Esophagus	ESCC	1.47e-13	6.30e-01	0.1067
4017	LOXL2	P62T-E	Human	Esophagus	ESCC	4.37e-02	1.31e-01	0.1302
4017	LOXL2	P74T-E	Human	Esophagus	ESCC	1.01e-09	4.45e-01	0.1479
4017	LOXL2	P76T-E	Human	Esophagus	ESCC	1.01e-04	2.26e-01	0.1207
4017	LOXL2	P79T-E	Human	Esophagus	ESCC	1.04e-07	2.28e-01	0.1154
4017	LOXL2	P89T-E	Human	Esophagus	ESCC	9.98e-08	5.59e-01	0.1752

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
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:0006091110	Esophagus	ESCC	generation of precursor metabolites and energy	331/8552	490/18723	3.86e-23	8.45e-21	331
GO:001820514	Esophagus	ESCC	peptidyl-lysine modification	259/8552	376/18723	3.90e-20	5.26e-18	259
GO:0022900110	Esophagus	ESCC	electron transport chain	133/8552	175/18723	2.18e-16	1.67e-14	133
GO:0070482111	Esophagus	ESCC	response to oxygen levels	218/8552	347/18723	6.91e-11	2.17e-09	218
GO:0036293111	Esophagus	ESCC	response to decreased oxygen levels	201/8552	322/18723	8.37e-10	2.04e-08	201
GO:0001666111	Esophagus	ESCC	response to hypoxia	192/8552	307/18723	1.59e-09	3.69e-08	192
GO:000632517	Esophagus	ESCC	chromatin organization	240/8552	409/18723	6.52e-08	1.14e-06	240
GO:000756820	Esophagus	ESCC	aging	201/8552	339/18723	2.64e-07	3.94e-06	201
GO:009872714	Esophagus	ESCC	maintenance of cell number	90/8552	134/18723	3.94e-07	5.43e-06	90
GO:001982714	Esophagus	ESCC	stem cell population maintenance	88/8552	131/18723	5.23e-07	6.97e-06	88
GO:00107184	Esophagus	ESCC	positive regulation of epithelial to mesenchymal transition	40/8552	52/18723	4.25e-06	4.56e-05	40
GO:001003827	Esophagus	ESCC	response to metal ion	208/8552	373/18723	5.02e-05	3.90e-04	208
GO:00301984	Esophagus	ESCC	extracellular matrix organization	171/8552	301/18723	6.08e-05	4.67e-04	171
GO:00430624	Esophagus	ESCC	extracellular structure organization	171/8552	302/18723	7.73e-05	5.76e-04	171
GO:00452294	Esophagus	ESCC	external encapsulating structure organization	172/8552	304/18723	7.80e-05	5.80e-04	172
GO:005067318	Esophagus	ESCC	epithelial cell proliferation	238/8552	437/18723	1.19e-04	8.20e-04	238
GO:00018378	Esophagus	ESCC	epithelial to mesenchymal transition	95/8552	157/18723	1.25e-04	8.56e-04	95
GO:00487628	Esophagus	ESCC	mesenchymal cell differentiation	133/8552	236/18723	5.94e-04	3.22e-03	133
GO:00107174	Esophagus	ESCC	regulation of epithelial to mesenchymal transition	61/8552	99/18723	1.01e-03	5.09e-03	61
GO:000166720	Esophagus	ESCC	ameboidal-type cell migration	250/8552	475/18723	1.22e-03	5.97e-03	250

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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

LOXL2

SNV

Missense_Mutation

novel

c.199N>A

p.His67Asn

p.H67N

Q9Y4K0

protein_coding

tolerated(0.24)

benign(0.087)

TCGA-5T-A9QA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxol

LOXL2

SNV

Missense_Mutation

c.447N>C

p.Lys149Asn

p.K149N

Q9Y4K0

protein_coding

tolerated(0.12)

benign(0.093)

TCGA-AQ-A0Y5-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

cytoxan

LOXL2

insertion

In_Frame_Ins

novel

c.1901_1902insAAATGTGTGTTTAATTTGTTATTC

p.Val634_Phe635insAsnValCysLeuIleCysTyrSer

p.V634_F635insNVCLICYS

Q9Y4K0

protein_coding

TCGA-A2-A0CT-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

LOXL2

deletion

Frame_Shift_Del

novel

c.1615delN

p.Ala539ProfsTer103

p.A539Pfs*103

Q9Y4K0

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

LOXL2

SNV

Missense_Mutation

rs768171524

c.2212N>A

p.Gly738Ser

p.G738S

Q9Y4K0

protein_coding

deleterious(0.01)

probably_damaging(0.993)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

LOXL2

SNV

Missense_Mutation

novel

c.877N>C

p.Asn293His

p.N293H

Q9Y4K0

protein_coding

tolerated(0.32)

benign(0.007)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

LOXL2

SNV

Missense_Mutation

novel

c.1295N>G

p.Gln432Arg

p.Q432R

Q9Y4K0

protein_coding

deleterious(0.03)

benign(0.009)

TCGA-C5-A2LZ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Unknown

LOXL2

SNV

Missense_Mutation

novel

c.96N>A

p.His32Gln

p.H32Q

Q9Y4K0

protein_coding

tolerated_low_confidence(0.12)

benign(0)

TCGA-VS-A953-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

LOXL2

SNV

Missense_Mutation

rs748831417

c.1322N>A

p.Arg441His

p.R441H

Q9Y4K0

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-VS-A9UJ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

LOXL2

SNV

Missense_Mutation

rs755780161

c.2068C>T

p.Arg690Cys

p.R690C

Q9Y4K0

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-A6-6653-01

Colorectum

colon 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
4017	LOXL2	DRUGGABLE GENOME, TRANSCRIPTION FACTOR, ENZYME		GS-6624	SIMTUZUMAB
4017	LOXL2	DRUGGABLE GENOME, TRANSCRIPTION FACTOR, ENZYME	inhibitor	385612245
4017	LOXL2	DRUGGABLE GENOME, TRANSCRIPTION FACTOR, ENZYME	inhibitor	CHEMBL2109667	SIMTUZUMAB
4017	LOXL2	DRUGGABLE GENOME, TRANSCRIPTION FACTOR, ENZYME	inhibitor	385612244
4017	LOXL2	DRUGGABLE GENOME, TRANSCRIPTION FACTOR, ENZYME	inhibitor	252166622	SIMTUZUMAB

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