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: NRDC

Gene summary for NRDC

Gene summary.

Gene information	Species	Human
	Gene symbol	NRDC
	Gene ID	4898
	Gene name	nardilysin convertase
	Gene Alias	NRD1
	Cytomap	1p32.3
	Gene Type	protein-coding
	GO ID	GO:0001659
	UniProtAcc	O43847

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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
4898	NRDC	HTA11_1938_2000001011	Human	Colorectum	AD	3.88e-12	7.38e-01	-0.0811
4898	NRDC	HTA11_347_2000001011	Human	Colorectum	AD	1.96e-13	6.89e-01	-0.1954
4898	NRDC	HTA11_1391_2000001011	Human	Colorectum	AD	4.01e-02	4.53e-01	-0.059
4898	NRDC	HTA11_99999970781_79442	Human	Colorectum	MSS	1.28e-02	4.56e-01	0.294
4898	NRDC	HTA11_99999965104_69814	Human	Colorectum	MSS	3.08e-03	5.06e-01	0.281
4898	NRDC	A001-C-207	Human	Colorectum	FAP	1.34e-04	-2.70e-01	0.1278
4898	NRDC	A015-C-203	Human	Colorectum	FAP	3.83e-28	-4.19e-01	-0.1294
4898	NRDC	A015-C-204	Human	Colorectum	FAP	5.33e-07	-3.40e-01	-0.0228
4898	NRDC	A014-C-040	Human	Colorectum	FAP	3.27e-04	-4.87e-01	-0.1184
4898	NRDC	A002-C-201	Human	Colorectum	FAP	2.91e-15	-4.47e-01	0.0324
4898	NRDC	A002-C-203	Human	Colorectum	FAP	2.20e-02	-1.17e-01	0.2786
4898	NRDC	A001-C-119	Human	Colorectum	FAP	1.13e-03	-2.66e-01	-0.1557
4898	NRDC	A001-C-108	Human	Colorectum	FAP	1.19e-14	-1.47e-01	-0.0272
4898	NRDC	A002-C-205	Human	Colorectum	FAP	6.95e-18	-2.36e-01	-0.1236
4898	NRDC	A001-C-104	Human	Colorectum	FAP	3.89e-02	-6.11e-02	0.0184
4898	NRDC	A015-C-005	Human	Colorectum	FAP	4.40e-03	-2.26e-01	-0.0336
4898	NRDC	A015-C-006	Human	Colorectum	FAP	8.27e-14	-3.33e-01	-0.0994
4898	NRDC	A015-C-106	Human	Colorectum	FAP	1.17e-11	-2.84e-01	-0.0511
4898	NRDC	A002-C-114	Human	Colorectum	FAP	2.55e-13	-2.77e-01	-0.1561
4898	NRDC	A015-C-104	Human	Colorectum	FAP	8.26e-27	-1.95e-01	-0.1899

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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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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:0042176	Colorectum	AD	regulation of protein catabolic process	160/3918	391/18723	1.06e-19	7.34e-17	160
GO:0009896	Colorectum	AD	positive regulation of catabolic process	180/3918	492/18723	4.33e-16	1.94e-13	180
GO:0031331	Colorectum	AD	positive regulation of cellular catabolic process	156/3918	427/18723	4.68e-14	1.05e-11	156
GO:0045732	Colorectum	AD	positive regulation of protein catabolic process	92/3918	231/18723	3.85e-11	4.47e-09	92
GO:0045862	Colorectum	AD	positive regulation of proteolysis	129/3918	372/18723	4.04e-10	3.46e-08	129
GO:0052547	Colorectum	AD	regulation of peptidase activity	137/3918	461/18723	4.12e-06	1.12e-04	137
GO:0052548	Colorectum	AD	regulation of endopeptidase activity	124/3918	432/18723	6.58e-05	1.07e-03	124
GO:0033619	Colorectum	AD	membrane protein proteolysis	21/3918	57/18723	4.16e-03	2.88e-02	21
GO:0106106	Colorectum	AD	cold-induced thermogenesis	43/3918	144/18723	7.05e-03	4.31e-02	43
GO:0120161	Colorectum	AD	regulation of cold-induced thermogenesis	43/3918	144/18723	7.05e-03	4.31e-02	43
GO:1990845	Colorectum	AD	adaptive thermogenesis	46/3918	157/18723	7.97e-03	4.73e-02	46
GO:00421762	Colorectum	MSS	regulation of protein catabolic process	145/3467	391/18723	2.03e-18	1.17e-15	145
GO:00098962	Colorectum	MSS	positive regulation of catabolic process	163/3467	492/18723	3.10e-15	9.22e-13	163
GO:00313312	Colorectum	MSS	positive regulation of cellular catabolic process	140/3467	427/18723	7.02e-13	1.33e-10	140
GO:00457322	Colorectum	MSS	positive regulation of protein catabolic process	85/3467	231/18723	3.66e-11	4.57e-09	85
GO:00458622	Colorectum	MSS	positive regulation of proteolysis	119/3467	372/18723	2.14e-10	2.09e-08	119
GO:00525472	Colorectum	MSS	regulation of peptidase activity	130/3467	461/18723	1.81e-07	8.13e-06	130
GO:00525482	Colorectum	MSS	regulation of endopeptidase activity	117/3467	432/18723	6.25e-06	1.65e-04	117
GO:00336191	Colorectum	MSS	membrane protein proteolysis	20/3467	57/18723	2.23e-03	1.84e-02	20
GO:0006509	Colorectum	MSS	membrane protein ectodomain proteolysis	15/3467	43/18723	8.06e-03	4.91e-02	15

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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

NRDC

SNV

Missense_Mutation

c.3193N>C

p.Glu1065Gln

p.E1065Q

protein_coding

deleterious(0.04)

possibly_damaging(0.905)

TCGA-5L-AAT0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

NRDC

SNV

Missense_Mutation

novel

c.2839N>C

p.Asp947His

p.D947H

protein_coding

deleterious(0.02)

benign(0.046)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

NRDC

SNV

Missense_Mutation

novel

c.890C>A

p.Pro297Gln

p.P297Q

protein_coding

tolerated(0.11)

probably_damaging(0.964)

TCGA-A2-A25A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Cytoxan

NRDC

SNV

Missense_Mutation

c.1057G>A

p.Glu353Lys

p.E353K

protein_coding

deleterious(0.04)

possibly_damaging(0.742)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NRDC

SNV

Missense_Mutation

novel

c.3062G>A

p.Arg1021Gln

p.R1021Q

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NRDC

SNV

Missense_Mutation

c.210N>C

p.Gln70His

p.Q70H

protein_coding

tolerated_low_confidence(0.06)

benign(0.276)

TCGA-AN-A0XN-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

NRDC

SNV

Missense_Mutation

c.766T>G

p.Ser256Ala

p.S256A

protein_coding

tolerated_low_confidence(0.45)

benign(0)

TCGA-BH-A0BQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

NRDC

SNV

Missense_Mutation

c.3389C>T

p.Ser1130Leu

p.S1130L

protein_coding

tolerated(0.21)

benign(0.001)

TCGA-C8-A26Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NRDC

SNV

Missense_Mutation

novel

c.520N>A

p.Asp174Asn

p.D174N

protein_coding

tolerated_low_confidence(0.3)

benign(0.021)

TCGA-GM-A2DO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

NRDC

insertion

Nonsense_Mutation

novel

c.3125_3126insCAAATAAATAAAC

p.Phe1043LysfsTer2

p.F1043Kfs*2

protein_coding

TCGA-AN-A03X-01

Breast

breast invasive 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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