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: EHMT2

Gene summary for EHMT2

Gene summary.

Gene information	Species	Human
	Gene symbol	EHMT2
	Gene ID	10919
	Gene name	euchromatic histone lysine methyltransferase 2
	Gene Alias	BAT8
	Cytomap	6p21.33
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	A2ABF8

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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
10919	EHMT2	HTA11_2487_2000001011	Human	Colorectum	SER	2.28e-05	3.32e-01	-0.1808
10919	EHMT2	HTA11_347_2000001011	Human	Colorectum	AD	4.40e-07	4.16e-01	-0.1954
10919	EHMT2	HTA11_696_2000001011	Human	Colorectum	AD	5.33e-15	5.82e-01	-0.1464
10919	EHMT2	HTA11_866_2000001011	Human	Colorectum	AD	2.84e-10	4.30e-01	-0.1001
10919	EHMT2	HTA11_1391_2000001011	Human	Colorectum	AD	1.62e-06	4.07e-01	-0.059
10919	EHMT2	HTA11_7696_3000711011	Human	Colorectum	AD	9.01e-04	2.55e-01	0.0674
10919	EHMT2	HTA11_99999965104_69814	Human	Colorectum	MSS	4.34e-03	3.67e-01	0.281
10919	EHMT2	HTA11_99999971662_82457	Human	Colorectum	MSS	2.69e-05	3.50e-01	0.3859
10919	EHMT2	A015-C-104	Human	Colorectum	FAP	2.37e-03	1.31e-01	-0.1899
10919	EHMT2	LZE4T	Human	Esophagus	ESCC	2.33e-08	2.29e-01	0.0811
10919	EHMT2	LZE7T	Human	Esophagus	ESCC	1.11e-12	3.64e-01	0.0667
10919	EHMT2	LZE20T	Human	Esophagus	ESCC	1.07e-09	2.71e-01	0.0662
10919	EHMT2	LZE22D1	Human	Esophagus	HGIN	2.08e-03	2.04e-01	0.0595
10919	EHMT2	LZE22T	Human	Esophagus	ESCC	6.37e-11	5.79e-01	0.068
10919	EHMT2	LZE24T	Human	Esophagus	ESCC	6.07e-15	4.44e-01	0.0596
10919	EHMT2	LZE6T	Human	Esophagus	ESCC	3.18e-03	2.45e-01	0.0845
10919	EHMT2	P1T-E	Human	Esophagus	ESCC	5.29e-10	5.19e-01	0.0875
10919	EHMT2	P2T-E	Human	Esophagus	ESCC	1.74e-67	9.25e-01	0.1177
10919	EHMT2	P4T-E	Human	Esophagus	ESCC	1.01e-35	6.99e-01	0.1323
10919	EHMT2	P5T-E	Human	Esophagus	ESCC	4.95e-18	4.08e-01	0.1327

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal 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
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma

∗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:00310601	Liver	HCC	regulation of histone methylation	46/7958	69/18723	4.30e-05	4.20e-04	46
GO:00349681	Liver	HCC	histone lysine methylation	70/7958	115/18723	5.32e-05	5.04e-04	70
GO:009730522	Liver	HCC	response to alcohol	138/7958	253/18723	6.91e-05	6.26e-04	138
GO:20007851	Liver	HCC	regulation of autophagosome assembly	28/7958	39/18723	2.02e-04	1.56e-03	28
GO:0016242	Liver	HCC	negative regulation of macroautophagy	25/7958	34/18723	2.42e-04	1.81e-03	25
GO:0000280	Liver	HCC	nuclear division	220/7958	439/18723	6.90e-04	4.25e-03	220
GO:1902116	Liver	HCC	negative regulation of organelle assembly	28/7958	41/18723	7.54e-04	4.55e-03	28
GO:00180221	Liver	HCC	peptidyl-lysine methylation	74/7958	131/18723	8.46e-04	5.06e-03	74
GO:00062751	Liver	HCC	regulation of DNA replication	60/7958	107/18723	3.15e-03	1.46e-02	60
GO:0051568	Liver	HCC	histone H3-K4 methylation	36/7958	59/18723	3.15e-03	1.46e-02	36
GO:0051569	Liver	HCC	regulation of histone H3-K4 methylation	21/7958	31/18723	4.01e-03	1.76e-02	21
GO:00714662	Liver	HCC	cellular response to xenobiotic stimulus	93/7958	177/18723	4.35e-03	1.89e-02	93
GO:00432791	Liver	HCC	response to alkaloid	62/7958	115/18723	8.79e-03	3.42e-02	62
GO:00454712	Liver	HCC	response to ethanol	72/7958	137/18723	1.10e-02	4.07e-02	72
GO:001623610	Oral cavity	OSCC	macroautophagy	192/7305	291/18723	7.01e-21	1.14e-18	192
GO:00165707	Oral cavity	OSCC	histone modification	270/7305	463/18723	1.59e-17	1.50e-15	270
GO:001050610	Oral cavity	OSCC	regulation of autophagy	198/7305	317/18723	1.63e-17	1.51e-15	198
GO:00070592	Oral cavity	OSCC	chromosome segregation	206/7305	346/18723	5.82e-15	3.76e-13	206
GO:00182056	Oral cavity	OSCC	peptidyl-lysine modification	216/7305	376/18723	2.32e-13	1.16e-11	216
GO:00062603	Oral cavity	OSCC	DNA replication	159/7305	260/18723	3.25e-13	1.59e-11	159

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa04211	Colorectum	AD	Longevity regulating pathway	33/2092	89/8465	6.15e-03	2.68e-02	1.71e-02	33
hsa042111	Colorectum	AD	Longevity regulating pathway	33/2092	89/8465	6.15e-03	2.68e-02	1.71e-02	33
hsa042112	Colorectum	MSS	Longevity regulating pathway	33/1875	89/8465	9.33e-04	5.58e-03	3.42e-03	33
hsa003102	Colorectum	MSS	Lysine degradation	24/1875	63/8465	2.94e-03	1.39e-02	8.50e-03	24
hsa042113	Colorectum	MSS	Longevity regulating pathway	33/1875	89/8465	9.33e-04	5.58e-03	3.42e-03	33
hsa003103	Colorectum	MSS	Lysine degradation	24/1875	63/8465	2.94e-03	1.39e-02	8.50e-03	24
hsa042114	Colorectum	FAP	Longevity regulating pathway	27/1404	89/8465	8.82e-04	5.20e-03	3.16e-03	27
hsa042115	Colorectum	FAP	Longevity regulating pathway	27/1404	89/8465	8.82e-04	5.20e-03	3.16e-03	27
hsa0421114	Esophagus	ESCC	Longevity regulating pathway	58/4205	89/8465	2.19e-03	6.16e-03	3.16e-03	58
hsa0031010	Esophagus	ESCC	Lysine degradation	41/4205	63/8465	9.63e-03	2.27e-02	1.16e-02	41
hsa0421115	Esophagus	ESCC	Longevity regulating pathway	58/4205	89/8465	2.19e-03	6.16e-03	3.16e-03	58
hsa0031013	Esophagus	ESCC	Lysine degradation	41/4205	63/8465	9.63e-03	2.27e-02	1.16e-02	41
hsa0031021	Liver	Cirrhotic	Lysine degradation	29/2530	63/8465	4.81e-03	1.74e-02	1.07e-02	29
hsa042118	Liver	Cirrhotic	Longevity regulating pathway	37/2530	89/8465	1.22e-02	3.89e-02	2.40e-02	37
hsa0031031	Liver	Cirrhotic	Lysine degradation	29/2530	63/8465	4.81e-03	1.74e-02	1.07e-02	29
hsa0421111	Liver	Cirrhotic	Longevity regulating pathway	37/2530	89/8465	1.22e-02	3.89e-02	2.40e-02	37
hsa0031041	Liver	HCC	Lysine degradation	47/4020	63/8465	1.02e-05	7.58e-05	4.22e-05	47
hsa0421121	Liver	HCC	Longevity regulating pathway	61/4020	89/8465	4.46e-05	2.37e-04	1.32e-04	61
hsa0031051	Liver	HCC	Lysine degradation	47/4020	63/8465	1.02e-05	7.58e-05	4.22e-05	47
hsa0421131	Liver	HCC	Longevity regulating pathway	61/4020	89/8465	4.46e-05	2.37e-04	1.32e-04	61

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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

EHMT2

SNV

Missense_Mutation

c.2509N>G

p.Thr837Ala

p.T837A

protein_coding

tolerated(0.35)

benign(0.055)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

EHMT2

SNV

Missense_Mutation

c.1972G>A

p.Ala658Thr

p.A658T

protein_coding

deleterious(0.03)

possibly_damaging(0.621)

TCGA-EW-A3U0-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

EHMT2

SNV

Missense_Mutation

novel

c.1651A>T

p.Asn551Tyr

p.N551Y

protein_coding

deleterious(0)

possibly_damaging(0.76)

TCGA-PE-A5DC-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

EHMT2

insertion

Frame_Shift_Ins

novel

c.2932_2933insTAACA

p.Glu978ValfsTer10

p.E978Vfs*10

protein_coding

TCGA-A2-A0EQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

EHMT2

insertion

In_Frame_Ins

novel

c.2931_2932insCCCACTGTT

p.Ser977_Glu978insProThrVal

p.S977_E978insPTV

protein_coding

TCGA-A2-A0EQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

EHMT2

insertion

Frame_Shift_Ins

novel

c.659_660insTGTTGTA

p.Gly221ValfsTer5

p.G221Vfs*5

protein_coding

TCGA-BH-A0HK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

EHMT2

SNV

Missense_Mutation

c.3496N>C

p.Asp1166His

p.D1166H

protein_coding

tolerated(0.08)

benign(0.075)

TCGA-C5-A1MH-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

EHMT2

SNV

Missense_Mutation

novel

c.2734N>A

p.Asp912Asn

p.D912N

protein_coding

tolerated(0.06)

benign(0.186)

TCGA-EK-A2RC-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

EHMT2

SNV

Missense_Mutation

c.3141N>C

p.Trp1047Cys

p.W1047C

protein_coding

tolerated(0.05)

possibly_damaging(0.732)

TCGA-IR-A3LH-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

EHMT2

SNV

Missense_Mutation

c.2911N>A

p.Glu971Lys

p.E971K

protein_coding

tolerated(0.33)

benign(0.106)

TCGA-JW-A5VL-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
10919	EHMT2	METHYL TRANSFERASE, ENZYME, DRUGGABLE GENOME		LISINOPRIL HYDRATE	LISINOPRIL HYDRATE
10919	EHMT2	METHYL TRANSFERASE, ENZYME, DRUGGABLE GENOME		DYCLONINE	DYCLONINE
10919	EHMT2	METHYL TRANSFERASE, ENZYME, DRUGGABLE GENOME		SJ000114950	CHEMBL606456
10919	EHMT2	METHYL TRANSFERASE, ENZYME, DRUGGABLE GENOME		WIN-552122	WIN-552122
10919	EHMT2	METHYL TRANSFERASE, ENZYME, DRUGGABLE GENOME		HISTAMINE	HISTAMINE
10919	EHMT2	METHYL TRANSFERASE, ENZYME, DRUGGABLE GENOME		N-(3-METHOXYPHENYL)ANTHRANILIC ACID	CHEMBL1328677
10919	EHMT2	METHYL TRANSFERASE, ENZYME, DRUGGABLE GENOME		MEDRONIC ACID	MEDRONIC ACID
10919	EHMT2	METHYL TRANSFERASE, ENZYME, DRUGGABLE GENOME		SJ000014858	CHEMBL591628
10919	EHMT2	METHYL TRANSFERASE, ENZYME, DRUGGABLE GENOME		TELMISARTAN	TELMISARTAN
10919	EHMT2	METHYL TRANSFERASE, ENZYME, DRUGGABLE GENOME		GNF-PF-989	CHEMBL583150

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