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: NREP

Gene summary for NREP

Gene summary.

Gene information	Species	Human
	Gene symbol	NREP
	Gene ID	9315
	Gene name	neuronal regeneration related protein
	Gene Alias	C5orf13
	Cytomap	5q22.1
	Gene Type	protein-coding
	GO ID	GO:0006950
	UniProtAcc	Q16612

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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
9315	NREP	AEH-subject1	Human	Endometrium	AEH	1.23e-12	-4.85e-01	-0.3059
9315	NREP	AEH-subject2	Human	Endometrium	AEH	1.02e-23	-5.22e-01	-0.2525
9315	NREP	AEH-subject3	Human	Endometrium	AEH	6.33e-17	-4.91e-01	-0.2576
9315	NREP	AEH-subject4	Human	Endometrium	AEH	2.25e-03	-2.19e-01	-0.2657
9315	NREP	AEH-subject5	Human	Endometrium	AEH	1.74e-15	-5.40e-01	-0.2953
9315	NREP	EEC-subject1	Human	Endometrium	EEC	9.63e-15	-4.78e-01	-0.2682
9315	NREP	EEC-subject2	Human	Endometrium	EEC	1.97e-20	-5.34e-01	-0.2607
9315	NREP	EEC-subject3	Human	Endometrium	EEC	2.00e-28	-5.51e-01	-0.2525
9315	NREP	EEC-subject4	Human	Endometrium	EEC	2.20e-27	-5.83e-01	-0.2571
9315	NREP	EEC-subject5	Human	Endometrium	EEC	3.93e-16	-5.17e-01	-0.249
9315	NREP	GSM5276934	Human	Endometrium	EEC	1.04e-27	-5.94e-01	-0.0913
9315	NREP	GSM5276937	Human	Endometrium	EEC	5.91e-23	-5.40e-01	-0.0897
9315	NREP	GSM6177620_NYU_UCEC1_lib1_lib1	Human	Endometrium	EEC	5.06e-23	-4.03e-01	-0.1869
9315	NREP	GSM6177620_NYU_UCEC1_lib2_lib2	Human	Endometrium	EEC	3.82e-21	-4.35e-01	-0.1875
9315	NREP	GSM6177620_NYU_UCEC1_lib3_lib3	Human	Endometrium	EEC	5.64e-22	-2.99e-01	-0.1883
9315	NREP	GSM6177621_NYU_UCEC2_lib1_lib1	Human	Endometrium	EEC	3.88e-17	-4.20e-01	-0.1934
9315	NREP	GSM6177622_NYU_UCEC3_lib1_lib1	Human	Endometrium	EEC	1.11e-22	-3.67e-01	-0.1917
9315	NREP	GSM6177622_NYU_UCEC3_lib2_lib2	Human	Endometrium	EEC	1.04e-37	-3.88e-01	-0.1916
9315	NREP	LZE7T	Human	Esophagus	ESCC	1.64e-02	6.10e-01	0.0667
9315	NREP	LZE8T	Human	Esophagus	ESCC	3.01e-02	8.46e-03	0.067

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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
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:00615648	Endometrium	AEH	axon development	88/2100	467/18723	6.39e-07	2.38e-05	88
GO:00715596	Endometrium	AEH	response to transforming growth factor beta	53/2100	256/18723	7.01e-06	1.69e-04	53
GO:00071787	Endometrium	AEH	transmembrane receptor protein serine/threonine kinase signaling pathway	67/2100	355/18723	1.28e-05	2.80e-04	67
GO:00715606	Endometrium	AEH	cellular response to transforming growth factor beta stimulus	51/2100	250/18723	1.59e-05	3.32e-04	51
GO:00310997	Endometrium	AEH	regeneration	41/2100	198/18723	7.29e-05	1.11e-03	41
GO:00071796	Endometrium	AEH	transforming growth factor beta receptor signaling pathway	38/2100	198/18723	6.41e-04	6.23e-03	38
GO:00900922	Endometrium	AEH	regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	43/2100	256/18723	4.47e-03	2.93e-02	43
GO:006156412	Endometrium	EEC	axon development	93/2168	467/18723	9.60e-08	4.69e-06	93
GO:003109914	Endometrium	EEC	regeneration	45/2168	198/18723	6.19e-06	1.49e-04	45
GO:007155914	Endometrium	EEC	response to transforming growth factor beta	54/2168	256/18723	8.25e-06	1.83e-04	54
GO:007156014	Endometrium	EEC	cellular response to transforming growth factor beta stimulus	52/2168	250/18723	1.81e-05	3.41e-04	52
GO:000717814	Endometrium	EEC	transmembrane receptor protein serine/threonine kinase signaling pathway	68/2168	355/18723	1.90e-05	3.50e-04	68
GO:000717914	Endometrium	EEC	transforming growth factor beta receptor signaling pathway	39/2168	198/18723	6.03e-04	5.98e-03	39
GO:0031102	Endometrium	EEC	neuron projection regeneration	15/2168	60/18723	2.88e-03	2.03e-02	15
GO:009009211	Endometrium	EEC	regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	44/2168	256/18723	4.72e-03	3.00e-02	44
GO:00311031	Endometrium	EEC	axon regeneration	13/2168	52/18723	5.34e-03	3.31e-02	13
GO:00486783	Endometrium	EEC	response to axon injury	18/2168	83/18723	6.04e-03	3.57e-02	18
GO:00715599	Esophagus	ESCC	response to transforming growth factor beta	157/8552	256/18723	2.95e-07	4.23e-06	157
GO:00715609	Esophagus	ESCC	cellular response to transforming growth factor beta stimulus	151/8552	250/18723	1.78e-06	2.10e-05	151
GO:003109910	Esophagus	ESCC	regeneration	122/8552	198/18723	4.26e-06	4.57e-05	122

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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

NREP

SNV

Missense_Mutation

c.245G>A

p.Arg82His

p.R82H

Q16612

protein_coding

deleterious(0.05)

probably_damaging(1)

TCGA-BH-A0B1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

adriamycin

NREP

SNV

Missense_Mutation

rs756211201

c.35N>A

p.Arg12Gln

p.R12Q

Q16612

protein_coding

deleterious_low_confidence(0)

benign(0)

TCGA-C8-A1HM-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

NREP

SNV

Missense_Mutation

c.224C>T

p.Pro75Leu

p.P75L

Q16612

protein_coding

deleterious(0.02)

probably_damaging(1)

TCGA-AA-3715-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

NREP

SNV

Missense_Mutation

c.245N>A

p.Arg82His

p.R82H

Q16612

protein_coding

deleterious(0.05)

probably_damaging(1)

TCGA-A5-A0G1-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

NREP

SNV

Missense_Mutation

rs1802827

c.290G>A

p.Gly97Asp

p.G97D

Q16612

protein_coding

deleterious(0.04)

possibly_damaging(0.836)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

NREP

SNV

Missense_Mutation

c.244N>T

p.Arg82Cys

p.R82C

Q16612

protein_coding

deleterious(0.01)

probably_damaging(1)

TCGA-AP-A051-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

NREP

SNV

Missense_Mutation

novel

c.314N>A

p.Arg105Lys

p.R105K

Q16612

protein_coding

tolerated(0.59)

benign(0.005)

TCGA-AP-A1DV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

NREP

SNV

Missense_Mutation

novel

c.314G>T

p.Arg105Ile

p.R105I

Q16612

protein_coding

deleterious(0.03)

benign(0.403)

TCGA-AP-A1E0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

NREP

SNV

Missense_Mutation

c.61N>G

p.Arg21Gly

p.R21G

Q16612

protein_coding

deleterious_low_confidence(0.02)

benign(0)

TCGA-B5-A0JN-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Chemotherapy

paclitaxel

NREP

SNV

Missense_Mutation

c.6A>C

p.Lys2Asn

p.K2N

Q16612

protein_coding

deleterious_low_confidence(0)

benign(0.007)

TCGA-D1-A103-01

Endometrium

uterine corpus endometrioid carcinoma

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

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