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: KDM1A

Gene summary for KDM1A

Gene summary.

Gene information	Species	Human
	Gene symbol	KDM1A
	Gene ID	23028
	Gene name	lysine demethylase 1A
	Gene Alias	AOF2
	Cytomap	1p36.12
	Gene Type	protein-coding
	GO ID	GO:0000018
	UniProtAcc	O60341

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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
23028	KDM1A	LZE4T	Human	Esophagus	ESCC	4.48e-02	6.20e-02	0.0811
23028	KDM1A	LZE20T	Human	Esophagus	ESCC	4.39e-02	1.20e-01	0.0662
23028	KDM1A	LZE24T	Human	Esophagus	ESCC	1.20e-05	2.14e-01	0.0596
23028	KDM1A	P1T-E	Human	Esophagus	ESCC	2.80e-08	2.74e-01	0.0875
23028	KDM1A	P2T-E	Human	Esophagus	ESCC	1.84e-58	9.23e-01	0.1177
23028	KDM1A	P4T-E	Human	Esophagus	ESCC	3.06e-17	4.34e-01	0.1323
23028	KDM1A	P5T-E	Human	Esophagus	ESCC	5.26e-16	3.03e-01	0.1327
23028	KDM1A	P8T-E	Human	Esophagus	ESCC	6.81e-12	1.67e-01	0.0889
23028	KDM1A	P9T-E	Human	Esophagus	ESCC	6.03e-17	1.68e-01	0.1131
23028	KDM1A	P10T-E	Human	Esophagus	ESCC	1.54e-25	4.72e-01	0.116
23028	KDM1A	P11T-E	Human	Esophagus	ESCC	9.05e-03	2.35e-01	0.1426
23028	KDM1A	P12T-E	Human	Esophagus	ESCC	1.57e-14	2.41e-01	0.1122
23028	KDM1A	P15T-E	Human	Esophagus	ESCC	5.24e-10	2.98e-01	0.1149
23028	KDM1A	P16T-E	Human	Esophagus	ESCC	9.99e-09	1.43e-01	0.1153
23028	KDM1A	P17T-E	Human	Esophagus	ESCC	3.63e-13	2.88e-01	0.1278
23028	KDM1A	P20T-E	Human	Esophagus	ESCC	1.04e-14	3.48e-01	0.1124
23028	KDM1A	P21T-E	Human	Esophagus	ESCC	1.28e-17	3.35e-01	0.1617
23028	KDM1A	P22T-E	Human	Esophagus	ESCC	5.86e-14	1.73e-01	0.1236
23028	KDM1A	P23T-E	Human	Esophagus	ESCC	3.15e-15	3.15e-01	0.108
23028	KDM1A	P24T-E	Human	Esophagus	ESCC	5.78e-13	2.29e-01	0.1287

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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
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:19022536	Lung	IAC	regulation of intrinsic apoptotic signaling pathway by p53 class mediator	12/2061	29/18723	2.64e-05	7.08e-04	12
GO:00510988	Lung	IAC	regulation of binding	66/2061	363/18723	2.78e-05	7.29e-04	66
GO:00435163	Lung	IAC	regulation of DNA damage response, signal transduction by p53 class mediator	13/2061	34/18723	3.34e-05	8.32e-04	13
GO:00510903	Lung	IAC	regulation of DNA-binding transcription factor activity	76/2061	440/18723	4.44e-05	1.05e-03	76
GO:00083808	Lung	IAC	RNA splicing	75/2061	434/18723	4.89e-05	1.12e-03	75
GO:20010207	Lung	IAC	regulation of response to DNA damage stimulus	44/2061	219/18723	5.50e-05	1.22e-03	44
GO:00510914	Lung	IAC	positive regulation of DNA-binding transcription factor activity	50/2061	260/18723	5.87e-05	1.29e-03	50
GO:00434017	Lung	IAC	steroid hormone mediated signaling pathway	31/2061	136/18723	6.00e-05	1.31e-03	31
GO:00313466	Lung	IAC	positive regulation of cell projection organization	63/2061	353/18723	7.37e-05	1.55e-03	63
GO:19033223	Lung	IAC	positive regulation of protein modification by small protein conjugation or removal	31/2061	138/18723	8.03e-05	1.65e-03	31
GO:00093147	Lung	IAC	response to radiation	77/2061	456/18723	8.59e-05	1.74e-03	77
GO:00219872	Lung	IAC	cerebral cortex development	27/2061	114/18723	8.78e-05	1.77e-03	27
GO:00714784	Lung	IAC	cellular response to radiation	38/2061	186/18723	1.19e-04	2.25e-03	38
GO:00511018	Lung	IAC	regulation of DNA binding	27/2061	118/18723	1.63e-04	2.93e-03	27
GO:00712146	Lung	IAC	cellular response to abiotic stimulus	58/2061	331/18723	2.30e-04	3.96e-03	58
GO:01040046	Lung	IAC	cellular response to environmental stimulus	58/2061	331/18723	2.30e-04	3.96e-03	58
GO:00325357	Lung	IAC	regulation of cellular component size	65/2061	383/18723	2.56e-04	4.26e-03	65
GO:0042692	Lung	IAC	muscle cell differentiation	65/2061	384/18723	2.75e-04	4.54e-03	65
GO:00165771	Lung	IAC	histone demethylation	11/2061	31/18723	2.91e-04	4.72e-03	11
GO:19022292	Lung	IAC	regulation of intrinsic apoptotic signaling pathway in response to DNA damage	12/2061	36/18723	3.05e-04	4.89e-03	12

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa04714211	Esophagus	ESCC	Thermogenesis	163/4205	232/8465	9.22e-11	1.14e-09	5.86e-10	163
hsa04714310	Esophagus	ESCC	Thermogenesis	163/4205	232/8465	9.22e-11	1.14e-09	5.86e-10	163
hsa0471422	Liver	HCC	Thermogenesis	170/4020	232/8465	5.36e-16	2.25e-14	1.25e-14	170
hsa0471432	Liver	HCC	Thermogenesis	170/4020	232/8465	5.36e-16	2.25e-14	1.25e-14	170
hsa0471416	Lung	IAC	Thermogenesis	46/1053	232/8465	7.85e-04	6.38e-03	4.23e-03	46
hsa0471417	Lung	IAC	Thermogenesis	46/1053	232/8465	7.85e-04	6.38e-03	4.23e-03	46
hsa0471430	Oral cavity	OSCC	Thermogenesis	138/3704	232/8465	7.67e-07	4.35e-06	2.22e-06	138
hsa04714113	Oral cavity	OSCC	Thermogenesis	138/3704	232/8465	7.67e-07	4.35e-06	2.22e-06	138
hsa0471428	Prostate	BPH	Thermogenesis	110/1718	232/8465	5.16e-21	1.42e-19	8.78e-20	110
hsa04714112	Prostate	BPH	Thermogenesis	110/1718	232/8465	5.16e-21	1.42e-19	8.78e-20	110
hsa0471429	Prostate	Tumor	Thermogenesis	110/1791	232/8465	1.56e-19	3.96e-18	2.46e-18	110
hsa0471437	Prostate	Tumor	Thermogenesis	110/1791	232/8465	1.56e-19	3.96e-18	2.46e-18	110

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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

KDM1A

SNV

Missense_Mutation

c.1189G>C

p.Glu397Gln

p.E397Q

O60341

protein_coding

tolerated(0.07)

possibly_damaging(0.552)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

KDM1A

SNV

Missense_Mutation

c.812G>A

p.Arg271Gln

p.R271Q

O60341

protein_coding

deleterious(0.04)

probably_damaging(0.941)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

KDM1A

SNV

Missense_Mutation

c.2426N>G

p.Ser809Trp

p.S809W

O60341

protein_coding

deleterious(0)

possibly_damaging(0.803)

TCGA-GM-A2D9-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

KDM1A

SNV

Missense_Mutation

c.1189N>A

p.Glu397Lys

p.E397K

O60341

protein_coding

deleterious(0.01)

benign(0.413)

TCGA-W8-A86G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

KDM1A

insertion

Nonsense_Mutation

novel

c.677_678insATAGAGATGGAGAAGAATATTATTCCAAGCATACATTAATGT

p.Thr226_Gln227insTer

p.T226_Q227ins*

O60341

protein_coding

TCGA-A2-A0CQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

KDM1A

insertion

Nonsense_Mutation

novel

c.1919_1920insGATGACAGTTGAGGATTCTGAAGTTGAC

p.Tyr640Ter

p.Y640*

O60341

protein_coding

TCGA-A8-A0A4-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

KDM1A

insertion

Frame_Shift_Ins

novel

c.1816_1817insGAGCGTGGTGGCTCATGCCTGTAATACCAGCACTT

p.Leu606ArgfsTer13

p.L606Rfs*13

O60341

protein_coding

TCGA-B6-A0IK-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

KDM1A

SNV

Missense_Mutation

c.817C>A

p.His273Asn

p.H273N

O60341

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-EA-A1QS-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

KDM1A

SNV

Missense_Mutation

novel

c.358T>C

p.Tyr120His

p.Y120H

O60341

protein_coding

deleterious_low_confidence(0.03)

probably_damaging(0.991)

TCGA-EA-A3HU-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

KDM1A

SNV

Missense_Mutation

novel

c.1844G>T

p.Arg615Leu

p.R615L

O60341

protein_coding

deleterious(0.02)

possibly_damaging(0.69)

TCGA-EK-A2IP-01

Cervix

cervical & endocervical cancer

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
23028	KDM1A	DRUGGABLE GENOME, ENZYME, CELL SURFACE, TRANSCRIPTION FACTOR COMPLEX, TRANSCRIPTION FACTOR BINDING	inhibitor	178103603
23028	KDM1A	DRUGGABLE GENOME, ENZYME, CELL SURFACE, TRANSCRIPTION FACTOR COMPLEX, TRANSCRIPTION FACTOR BINDING	inhibitor	310264760
23028	KDM1A	DRUGGABLE GENOME, ENZYME, CELL SURFACE, TRANSCRIPTION FACTOR COMPLEX, TRANSCRIPTION FACTOR BINDING		TRANYLCYPROMINE HYDROCHLORIDE	TRANYLCYPROMINE HYDROCHLORIDE
23028	KDM1A	DRUGGABLE GENOME, ENZYME, CELL SURFACE, TRANSCRIPTION FACTOR COMPLEX, TRANSCRIPTION FACTOR BINDING		2-[N-(PHTHALIMIDO)]ETHYL CARBAMIMIDOTHIOATE HCL	CHEMBL2182009	22876979
23028	KDM1A	DRUGGABLE GENOME, ENZYME, CELL SURFACE, TRANSCRIPTION FACTOR COMPLEX, TRANSCRIPTION FACTOR BINDING	inhibitor	249565921
23028	KDM1A	DRUGGABLE GENOME, ENZYME, CELL SURFACE, TRANSCRIPTION FACTOR COMPLEX, TRANSCRIPTION FACTOR BINDING	activator	252166601
23028	KDM1A	DRUGGABLE GENOME, ENZYME, CELL SURFACE, TRANSCRIPTION FACTOR COMPLEX, TRANSCRIPTION FACTOR BINDING	inhibitor	178103602
23028	KDM1A	DRUGGABLE GENOME, ENZYME, CELL SURFACE, TRANSCRIPTION FACTOR COMPLEX, TRANSCRIPTION FACTOR BINDING	inhibitor	178101964	TRANYLCYPROMINE
23028	KDM1A	DRUGGABLE GENOME, ENZYME, CELL SURFACE, TRANSCRIPTION FACTOR COMPLEX, TRANSCRIPTION FACTOR BINDING		PARNATE	PARNATE	21382717
23028	KDM1A	DRUGGABLE GENOME, ENZYME, CELL SURFACE, TRANSCRIPTION FACTOR COMPLEX, TRANSCRIPTION FACTOR BINDING		NAMOLINE	NAMOLINE	24007511

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