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: EPHX1

Gene summary for EPHX1

Gene summary.

Gene information	Species	Human
	Gene symbol	EPHX1
	Gene ID	2052
	Gene name	epoxide hydrolase 1
	Gene Alias	EPHX
	Cytomap	1q42.12
	Gene Type	protein-coding
	GO ID	GO:0001676
	UniProtAcc	P07099

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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
2052	EPHX1	HTA11_347_2000001011	Human	Colorectum	AD	1.17e-04	3.35e-01	-0.1954
2052	EPHX1	HTA11_7696_3000711011	Human	Colorectum	AD	2.29e-02	1.99e-01	0.0674
2052	EPHX1	HTA11_99999971662_82457	Human	Colorectum	MSS	4.49e-10	4.55e-01	0.3859
2052	EPHX1	A018-E-020	Human	Colorectum	FAP	1.04e-02	-1.10e-01	-0.2034
2052	EPHX1	LZE2T	Human	Esophagus	ESCC	2.16e-09	2.49e+00	0.082
2052	EPHX1	LZE4T	Human	Esophagus	ESCC	4.96e-23	1.36e+00	0.0811
2052	EPHX1	LZE5T	Human	Esophagus	ESCC	1.03e-10	1.57e+00	0.0514
2052	EPHX1	LZE7T	Human	Esophagus	ESCC	5.40e-06	9.81e-01	0.0667
2052	EPHX1	LZE8T	Human	Esophagus	ESCC	3.55e-16	1.05e+00	0.067
2052	EPHX1	LZE20T	Human	Esophagus	ESCC	2.86e-09	1.00e+00	0.0662
2052	EPHX1	LZE22D1	Human	Esophagus	HGIN	1.34e-03	9.78e-01	0.0595
2052	EPHX1	LZE22T	Human	Esophagus	ESCC	7.72e-13	2.17e+00	0.068
2052	EPHX1	LZE24T	Human	Esophagus	ESCC	3.67e-23	1.05e+00	0.0596
2052	EPHX1	LZE21T	Human	Esophagus	ESCC	3.36e-05	1.10e+00	0.0655
2052	EPHX1	P1T-E	Human	Esophagus	ESCC	5.60e-15	1.44e+00	0.0875
2052	EPHX1	P2T-E	Human	Esophagus	ESCC	7.38e-28	7.53e-01	0.1177
2052	EPHX1	P4T-E	Human	Esophagus	ESCC	9.77e-30	9.73e-01	0.1323
2052	EPHX1	P5T-E	Human	Esophagus	ESCC	1.05e-13	5.21e-01	0.1327
2052	EPHX1	P8T-E	Human	Esophagus	ESCC	8.43e-81	1.89e+00	0.0889
2052	EPHX1	P9T-E	Human	Esophagus	ESCC	4.72e-50	1.99e+00	0.1131

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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
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:0019439	Colorectum	AD	aromatic compound catabolic process	146/3918	467/18723	7.48e-08	3.84e-06	146
GO:0009636	Colorectum	AD	response to toxic substance	88/3918	262/18723	1.12e-06	3.72e-05	88
GO:0006631	Colorectum	AD	fatty acid metabolic process	114/3918	390/18723	5.58e-05	9.44e-04	114
GO:0009410	Colorectum	AD	response to xenobiotic stimulus	128/3918	462/18723	2.69e-04	3.31e-03	128
GO:0018904	Colorectum	AD	ether metabolic process	14/3918	27/18723	3.72e-04	4.29e-03	14
GO:00194392	Colorectum	MSS	aromatic compound catabolic process	140/3467	467/18723	8.56e-10	6.85e-08	140
GO:00096362	Colorectum	MSS	response to toxic substance	73/3467	262/18723	1.26e-04	1.94e-03	73
GO:00066312	Colorectum	MSS	fatty acid metabolic process	95/3467	390/18723	2.20e-03	1.84e-02	95
GO:00094101	Colorectum	MSS	response to xenobiotic stimulus	110/3467	462/18723	2.36e-03	1.92e-02	110
GO:00194394	Colorectum	FAP	aromatic compound catabolic process	100/2622	467/18723	6.75e-06	2.08e-04	100
GO:00066313	Colorectum	FAP	fatty acid metabolic process	81/2622	390/18723	1.43e-04	2.24e-03	81
GO:00094102	Colorectum	FAP	response to xenobiotic stimulus	87/2622	462/18723	2.15e-03	1.77e-02	87
GO:00189042	Colorectum	FAP	ether metabolic process	10/2622	27/18723	2.46e-03	1.95e-02	10
GO:00096363	Colorectum	FAP	response to toxic substance	53/2622	262/18723	3.35e-03	2.46e-02	53
GO:001943917	Esophagus	HGIN	aromatic compound catabolic process	105/2587	467/18723	1.89e-07	9.31e-06	105
GO:001943918	Esophagus	ESCC	aromatic compound catabolic process	295/8552	467/18723	1.09e-14	5.98e-13	295
GO:00066318	Esophagus	ESCC	fatty acid metabolic process	217/8552	390/18723	4.21e-05	3.39e-04	217
GO:000941020	Esophagus	ESCC	response to xenobiotic stimulus	253/8552	462/18723	4.55e-05	3.58e-04	253
GO:000963620	Esophagus	ESCC	response to toxic substance	150/8552	262/18723	1.00e-04	7.12e-04	150
GO:00066316	Liver	NAFLD	fatty acid metabolic process	92/1882	390/18723	3.38e-15	3.29e-12	92

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05208	Colorectum	AD	Chemical carcinogenesis - reactive oxygen species	126/2092	223/8465	1.01e-24	1.68e-22	1.07e-22	126
hsa052081	Colorectum	AD	Chemical carcinogenesis - reactive oxygen species	126/2092	223/8465	1.01e-24	1.68e-22	1.07e-22	126
hsa052084	Colorectum	MSS	Chemical carcinogenesis - reactive oxygen species	118/1875	223/8465	2.71e-24	4.54e-22	2.78e-22	118
hsa052085	Colorectum	MSS	Chemical carcinogenesis - reactive oxygen species	118/1875	223/8465	2.71e-24	4.54e-22	2.78e-22	118
hsa052088	Colorectum	FAP	Chemical carcinogenesis - reactive oxygen species	78/1404	223/8465	1.08e-11	1.80e-09	1.09e-09	78
hsa052089	Colorectum	FAP	Chemical carcinogenesis - reactive oxygen species	78/1404	223/8465	1.08e-11	1.80e-09	1.09e-09	78
hsa0520839	Esophagus	HGIN	Chemical carcinogenesis - reactive oxygen species	92/1383	223/8465	2.41e-19	9.83e-18	7.80e-18	92
hsa05208115	Esophagus	HGIN	Chemical carcinogenesis - reactive oxygen species	92/1383	223/8465	2.41e-19	9.83e-18	7.80e-18	92
hsa05208211	Esophagus	ESCC	Chemical carcinogenesis - reactive oxygen species	168/4205	223/8465	1.83e-15	6.81e-14	3.49e-14	168
hsa05208310	Esophagus	ESCC	Chemical carcinogenesis - reactive oxygen species	168/4205	223/8465	1.83e-15	6.81e-14	3.49e-14	168
hsa0520814	Liver	NAFLD	Chemical carcinogenesis - reactive oxygen species	44/1043	223/8465	9.22e-04	1.31e-02	1.06e-02	44
hsa049762	Liver	NAFLD	Bile secretion	20/1043	89/8465	5.08e-03	4.43e-02	3.57e-02	20
hsa0520815	Liver	NAFLD	Chemical carcinogenesis - reactive oxygen species	44/1043	223/8465	9.22e-04	1.31e-02	1.06e-02	44
hsa0497611	Liver	NAFLD	Bile secretion	20/1043	89/8465	5.08e-03	4.43e-02	3.57e-02	20
hsa0520822	Liver	Cirrhotic	Chemical carcinogenesis - reactive oxygen species	121/2530	223/8465	1.35e-14	4.08e-13	2.52e-13	121
hsa0520832	Liver	Cirrhotic	Chemical carcinogenesis - reactive oxygen species	121/2530	223/8465	1.35e-14	4.08e-13	2.52e-13	121
hsa0520842	Liver	HCC	Chemical carcinogenesis - reactive oxygen species	167/4020	223/8465	2.85e-17	1.91e-15	1.06e-15	167
hsa0520852	Liver	HCC	Chemical carcinogenesis - reactive oxygen species	167/4020	223/8465	2.85e-17	1.91e-15	1.06e-15	167
hsa0520862	Liver	Cyst	Chemical carcinogenesis - reactive oxygen species	40/339	223/8465	4.80e-16	3.45e-14	2.85e-14	40
hsa0520872	Liver	Cyst	Chemical carcinogenesis - reactive oxygen species	40/339	223/8465	4.80e-16	3.45e-14	2.85e-14	40

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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

EPHX1

SNV

Missense_Mutation

rs556212945

c.1072N>A

p.Val358Ile

p.V358I

P07099

protein_coding

tolerated(0.42)

benign(0.078)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

EPHX1

SNV

Missense_Mutation

c.427C>T

p.Pro143Ser

p.P143S

P07099

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-AO-A0JF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

EPHX1

SNV

Missense_Mutation

c.598N>G

p.Asn200Asp

p.N200D

P07099

protein_coding

tolerated(0.88)

benign(0.042)

TCGA-AR-A250-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

EPHX1

SNV

Missense_Mutation

novel

c.950N>G

p.Ser317Cys

p.S317C

P07099

protein_coding

deleterious(0.02)

possibly_damaging(0.651)

TCGA-C8-A8HP-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

5-fluorouracil

EPHX1

insertion

In_Frame_Ins

novel

c.958_959insTTTTAAGCAACTTCTCTACCCTGACCCTCCTCCTGGGACAGC

p.Gly320delinsValLeuSerAsnPheSerThrLeuThrLeuLeuLeuGlyGlnArg

p.G320delinsVLSNFSTLTLLLGQR

P07099

protein_coding

TCGA-A2-A04T-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

EPHX1

deletion

Frame_Shift_Del

novel

c.684delG

p.Ser229ProfsTer2

p.S229Pfs*2

P07099

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

EPHX1

deletion

Frame_Shift_Del

novel

c.794delG

p.Gly265AspfsTer29

p.G265Dfs*29

P07099

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

EPHX1

SNV

Missense_Mutation

c.146G>A

p.Arg49His

p.R49H

P07099

protein_coding

tolerated(0.1)

benign(0.036)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

EPHX1

SNV

Missense_Mutation

rs371279887

c.800N>A

p.Arg267His

p.R267H

P07099

protein_coding

tolerated(0.27)

benign(0.003)

TCGA-5M-AAT6-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Unknown

EPHX1

SNV

Missense_Mutation

c.335N>T

p.Arg112Ile

p.R112I

P07099

protein_coding

deleterious(0)

benign(0.026)

TCGA-A6-3809-01

Colorectum

colon adenocarcinoma

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
2052	EPHX1	ENZYME, DRUGGABLE GENOME		docetaxel	DOCETAXEL	20157331
2052	EPHX1	ENZYME, DRUGGABLE GENOME		phenytoin	PHENYTOIN	19952982
2052	EPHX1	ENZYME, DRUGGABLE GENOME		phenprocoumon	PHENPROCOUMON	21057703
2052	EPHX1	ENZYME, DRUGGABLE GENOME		AR9281	AR9281
2052	EPHX1	ENZYME, DRUGGABLE GENOME		cisplatin	CISPLATIN	24533712
2052	EPHX1	ENZYME, DRUGGABLE GENOME		ANTICONVULSANT		10554101
2052	EPHX1	ENZYME, DRUGGABLE GENOME		cyclophosphamide	CYCLOPHOSPHAMIDE	24533712
2052	EPHX1	ENZYME, DRUGGABLE GENOME		carbamazepine	CARBAMAZEPINE	15692831,22188362,26314341,25495409,19620853

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