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: EPHA7

Gene summary for EPHA7

Gene summary.

Gene information	Species	Human
	Gene symbol	EPHA7
	Gene ID	2045
	Gene name	EPH receptor A7
	Gene Alias	EHK-3
	Cytomap	6q16.1
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	Q15375

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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
2045	EPHA7	P8T-E	Human	Esophagus	ESCC	1.66e-02	7.12e-02	0.0889
2045	EPHA7	P10T-E	Human	Esophagus	ESCC	3.75e-03	1.15e-01	0.116
2045	EPHA7	P12T-E	Human	Esophagus	ESCC	1.66e-02	8.52e-02	0.1122
2045	EPHA7	P15T-E	Human	Esophagus	ESCC	2.74e-15	4.01e-01	0.1149
2045	EPHA7	P16T-E	Human	Esophagus	ESCC	2.55e-31	5.03e-01	0.1153
2045	EPHA7	P20T-E	Human	Esophagus	ESCC	1.70e-02	1.18e-01	0.1124
2045	EPHA7	P27T-E	Human	Esophagus	ESCC	3.28e-14	2.36e-01	0.1055
2045	EPHA7	P56T-E	Human	Esophagus	ESCC	8.29e-08	8.20e-01	0.1613
2045	EPHA7	P57T-E	Human	Esophagus	ESCC	7.90e-03	8.25e-02	0.0926
2045	EPHA7	P61T-E	Human	Esophagus	ESCC	4.89e-16	3.72e-01	0.099
2045	EPHA7	P62T-E	Human	Esophagus	ESCC	1.03e-25	5.04e-01	0.1302
2045	EPHA7	P76T-E	Human	Esophagus	ESCC	9.20e-06	1.27e-01	0.1207

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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

∗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:2000116111	Esophagus	ESCC	regulation of cysteine-type endopeptidase activity	158/8552	235/18723	1.67e-11	5.90e-10	158
GO:0043281111	Esophagus	ESCC	regulation of cysteine-type endopeptidase activity involved in apoptotic process	143/8552	209/18723	2.12e-11	7.31e-10	143
GO:0016049110	Esophagus	ESCC	cell growth	289/8552	482/18723	1.29e-10	3.77e-09	289
GO:0052547111	Esophagus	ESCC	regulation of peptidase activity	275/8552	461/18723	7.54e-10	1.88e-08	275
GO:000155819	Esophagus	ESCC	regulation of cell growth	248/8552	414/18723	2.97e-09	6.45e-08	248
GO:0070997111	Esophagus	ESCC	neuron death	216/8552	361/18723	3.49e-08	6.45e-07	216
GO:0052548111	Esophagus	ESCC	regulation of endopeptidase activity	253/8552	432/18723	3.68e-08	6.78e-07	253
GO:003253520	Esophagus	ESCC	regulation of cellular component size	227/8552	383/18723	4.77e-08	8.60e-07	227
GO:004677710	Esophagus	ESCC	protein autophosphorylation	138/8552	227/18723	2.98e-06	3.38e-05	138
GO:0051402110	Esophagus	ESCC	neuron apoptotic process	148/8552	246/18723	3.08e-06	3.47e-05	148
GO:1901214111	Esophagus	ESCC	regulation of neuron death	186/8552	319/18723	3.35e-06	3.73e-05	186
GO:003367420	Esophagus	ESCC	positive regulation of kinase activity	260/8552	467/18723	7.26e-06	7.22e-05	260
GO:00459267	Esophagus	ESCC	negative regulation of growth	148/8552	249/18723	7.88e-06	7.73e-05	148
GO:006056210	Esophagus	ESCC	epithelial tube morphogenesis	187/8552	325/18723	9.95e-06	9.44e-05	187
GO:1901216111	Esophagus	ESCC	positive regulation of neuron death	65/8552	97/18723	1.76e-05	1.56e-04	65
GO:005076710	Esophagus	ESCC	regulation of neurogenesis	203/8552	364/18723	6.10e-05	4.68e-04	203
GO:00083619	Esophagus	ESCC	regulation of cell size	107/8552	181/18723	1.81e-04	1.16e-03	107
GO:006156415	Esophagus	ESCC	axon development	251/8552	467/18723	2.41e-04	1.49e-03	251
GO:001097516	Esophagus	ESCC	regulation of neuron projection development	240/8552	445/18723	2.48e-04	1.53e-03	240
GO:0043525110	Esophagus	ESCC	positive regulation of neuron apoptotic process	40/8552	58/18723	2.83e-04	1.71e-03	40

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0436016	Esophagus	ESCC	Axon guidance	108/4205	182/8465	5.13e-03	1.30e-02	6.67e-03	108
hsa0436017	Esophagus	ESCC	Axon guidance	108/4205	182/8465	5.13e-03	1.30e-02	6.67e-03	108

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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
EFNA1	EPHA7	EFNA1_EPHA7	EPHA	Prostate	ADJ
EFNA1	EPHA7	EFNA1_EPHA7	EPHA	Prostate	BPH

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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

EPHA7

SNV

Missense_Mutation

c.1765G>A

p.Asp589Asn

p.D589N

Q15375

protein_coding

tolerated(0.36)

benign(0.035)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

EPHA7

SNV

Missense_Mutation

rs755032746

c.2656N>C

p.Ile886Leu

p.I886L

Q15375

protein_coding

deleterious(0.04)

probably_damaging(0.997)

TCGA-AC-A3TN-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

EPHA7

SNV

Missense_Mutation

c.2683N>G

p.Arg895Gly

p.R895G

Q15375

protein_coding

deleterious(0)

benign(0.442)

TCGA-AN-A0FJ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

EPHA7

SNV

Missense_Mutation

c.1975N>A

p.Asp659Asn

p.D659N

Q15375

protein_coding

deleterious(0)

benign(0.116)

TCGA-AO-A0JC-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

fluorouracil

EPHA7

SNV

Missense_Mutation

rs779416238

c.1370N>A

p.Arg457Gln

p.R457Q

Q15375

protein_coding

tolerated(0.12)

benign(0.006)

TCGA-AR-A2LQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

docetaxel

EPHA7

SNV

Missense_Mutation

c.1441N>A

p.Tyr481Asn

p.Y481N

Q15375

protein_coding

deleterious(0)

probably_damaging(0.971)

TCGA-B6-A0RT-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

EPHA7

SNV

Missense_Mutation

c.1885N>C

p.Asp629His

p.D629H

Q15375

protein_coding

tolerated(0.09)

probably_damaging(0.996)

TCGA-BH-A0EE-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

docetaxel

EPHA7

SNV

Missense_Mutation

c.836N>T

p.Cys279Phe

p.C279F

Q15375

protein_coding

deleterious(0)

possibly_damaging(0.737)

TCGA-E2-A14Z-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

EPHA7

SNV

Missense_Mutation

novel

c.607A>G

p.Lys203Glu

p.K203E

Q15375

protein_coding

deleterious(0)

probably_damaging(0.986)

TCGA-OL-A66J-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

EPHA7

insertion

Nonsense_Mutation

novel

c.2271_2272insTATTGCCATAAATAATATATCAGTTATTATACATATTTAAAATGT

p.Arg757_Asp758insTyrCysHisLysTerTyrIleSerTyrTyrThrTyrLeuLysCys

p.R757_D758insYCHK*YISYYTYLKC

Q15375

protein_coding

TCGA-A8-A09D-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

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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
2045	EPHA7	CLINICALLY ACTIONABLE, KINASE, DRUGGABLE GENOME, TYROSINE KINASE	inhibitor	HESPERADIN	HESPERADIN	19035792
2045	EPHA7	CLINICALLY ACTIONABLE, KINASE, DRUGGABLE GENOME, TYROSINE KINASE	inhibitor	381118815
2045	EPHA7	CLINICALLY ACTIONABLE, KINASE, DRUGGABLE GENOME, TYROSINE KINASE	inhibitor	249565821
2045	EPHA7	CLINICALLY ACTIONABLE, KINASE, DRUGGABLE GENOME, TYROSINE KINASE	inhibitor	249565850
2045	EPHA7	CLINICALLY ACTIONABLE, KINASE, DRUGGABLE GENOME, TYROSINE KINASE	inhibitor	CHEMBL24828	VANDETANIB

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