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:00071799	Esophagus	ESCC	transforming growth factor beta receptor signaling pathway	121/8552	198/18723	8.26e-06	8.03e-05	121
GO:00311033	Esophagus	ESCC	axon regeneration	37/8552	52/18723	1.75e-04	1.14e-03	37
GO:006156415	Esophagus	ESCC	axon development	251/8552	467/18723	2.41e-04	1.49e-03	251
GO:000717810	Esophagus	ESCC	transmembrane receptor protein serine/threonine kinase signaling pathway	195/8552	355/18723	2.58e-04	1.58e-03	195
GO:00311024	Esophagus	ESCC	neuron projection regeneration	41/8552	60/18723	3.25e-04	1.91e-03	41
GO:00170156	Esophagus	ESCC	regulation of transforming growth factor beta receptor signaling pathway	75/8552	128/18723	2.19e-03	9.71e-03	75
GO:00486785	Esophagus	ESCC	response to axon injury	51/8552	83/18723	2.74e-03	1.16e-02	51
GO:19038447	Esophagus	ESCC	regulation of cellular response to transforming growth factor beta stimulus	76/8552	131/18723	2.96e-03	1.24e-02	76
GO:007155921	Liver	HCC	response to transforming growth factor beta	141/7958	256/18723	3.08e-05	3.16e-04	141
GO:007156021	Liver	HCC	cellular response to transforming growth factor beta stimulus	137/7958	250/18723	5.47e-05	5.14e-04	137
GO:00310992	Liver	HCC	regeneration	107/7958	198/18723	6.67e-04	4.12e-03	107
GO:000717921	Liver	HCC	transforming growth factor beta receptor signaling pathway	106/7958	198/18723	1.09e-03	6.23e-03	106
GO:19038442	Liver	HCC	regulation of cellular response to transforming growth factor beta stimulus	72/7958	131/18723	2.65e-03	1.27e-02	72
GO:001701511	Liver	HCC	regulation of transforming growth factor beta receptor signaling pathway	70/7958	128/18723	3.56e-03	1.59e-02	70
GO:00310999	Oral cavity	OSCC	regeneration	114/7305	198/18723	8.54e-08	1.50e-06	114
GO:00715598	Oral cavity	OSCC	response to transforming growth factor beta	140/7305	256/18723	2.34e-07	3.70e-06	140
GO:00715608	Oral cavity	OSCC	cellular response to transforming growth factor beta stimulus	137/7305	250/18723	2.68e-07	4.15e-06	137
GO:00071798	Oral cavity	OSCC	transforming growth factor beta receptor signaling pathway	109/7305	198/18723	3.21e-06	3.86e-05	109
GO:00170155	Oral cavity	OSCC	regulation of transforming growth factor beta receptor signaling pathway	71/7305	128/18723	1.14e-04	8.34e-04	71
GO:19038446	Oral cavity	OSCC	regulation of cellular response to transforming growth factor beta stimulus	72/7305	131/18723	1.51e-04	1.06e-03	72

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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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