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: CNDP2

Gene summary for CNDP2

Gene summary.

Gene information	Species	Human
	Gene symbol	CNDP2
	Gene ID	55748
	Gene name	carnosine dipeptidase 2
	Gene Alias	CN2
	Cytomap	18q22.3
	Gene Type	protein-coding
	GO ID	GO:0006508
	UniProtAcc	Q96KP4

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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
55748	CNDP2	GSM4909281	Human	Breast	IDC	2.55e-04	3.34e-01	0.21
55748	CNDP2	GSM4909294	Human	Breast	IDC	6.73e-03	-1.60e-01	0.2022
55748	CNDP2	GSM4909296	Human	Breast	IDC	3.14e-02	-6.52e-02	0.1524
55748	CNDP2	GSM4909297	Human	Breast	IDC	1.56e-03	-3.97e-02	0.1517
55748	CNDP2	GSM4909311	Human	Breast	IDC	2.33e-17	-7.54e-02	0.1534
55748	CNDP2	GSM4909312	Human	Breast	IDC	7.30e-07	2.58e-02	0.1552
55748	CNDP2	GSM4909319	Human	Breast	IDC	4.68e-19	-1.90e-01	0.1563
55748	CNDP2	GSM4909321	Human	Breast	IDC	1.10e-06	-6.32e-02	0.1559
55748	CNDP2	brca2	Human	Breast	Precancer	6.79e-05	2.49e-01	-0.024
55748	CNDP2	brca3	Human	Breast	Precancer	8.07e-06	2.91e-01	-0.0263
55748	CNDP2	NCCBC11	Human	Breast	DCIS	3.29e-06	5.37e-01	0.1232
55748	CNDP2	NCCBC3	Human	Breast	DCIS	5.65e-03	1.70e-01	0.1198
55748	CNDP2	NCCBC6	Human	Breast	DCIS	4.66e-11	8.72e-01	0.2095
55748	CNDP2	P1	Human	Breast	IDC	6.09e-04	-4.29e-02	0.1527
55748	CNDP2	DCIS2	Human	Breast	DCIS	1.67e-46	9.14e-02	0.0085
55748	CNDP2	HTA11_3410_2000001011	Human	Colorectum	AD	2.19e-05	4.18e-01	0.0155
55748	CNDP2	HTA11_2487_2000001011	Human	Colorectum	SER	3.40e-03	4.20e-01	-0.1808
55748	CNDP2	HTA11_1938_2000001011	Human	Colorectum	AD	7.61e-15	8.73e-01	-0.0811
55748	CNDP2	HTA11_78_2000001011	Human	Colorectum	AD	4.80e-05	6.00e-01	-0.1088
55748	CNDP2	HTA11_347_2000001011	Human	Colorectum	AD	3.16e-23	7.91e-01	-0.1954

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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
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
Prostate		BPH: Benign Prostatic Hyperplasia
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

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa00330	Colorectum	AD	Arginine and proline metabolism	23/2092	50/8465	8.27e-04	5.90e-03	3.76e-03	23
hsa003301	Colorectum	AD	Arginine and proline metabolism	23/2092	50/8465	8.27e-04	5.90e-03	3.76e-03	23
hsa003302	Colorectum	SER	Arginine and proline metabolism	17/1580	50/8465	7.12e-03	3.77e-02	2.74e-02	17
hsa003303	Colorectum	SER	Arginine and proline metabolism	17/1580	50/8465	7.12e-03	3.77e-02	2.74e-02	17
hsa003304	Colorectum	MSS	Arginine and proline metabolism	23/1875	50/8465	1.52e-04	1.24e-03	7.61e-04	23
hsa003305	Colorectum	MSS	Arginine and proline metabolism	23/1875	50/8465	1.52e-04	1.24e-03	7.61e-04	23
hsa003306	Colorectum	FAP	Arginine and proline metabolism	16/1404	50/8465	5.33e-03	2.10e-02	1.27e-02	16
hsa003307	Colorectum	FAP	Arginine and proline metabolism	16/1404	50/8465	5.33e-03	2.10e-02	1.27e-02	16
hsa00410	Liver	Cirrhotic	beta-Alanine metabolism	18/2530	31/8465	1.00e-03	5.57e-03	3.43e-03	18
hsa003308	Liver	Cirrhotic	Arginine and proline metabolism	25/2530	50/8465	2.18e-03	9.41e-03	5.80e-03	25
hsa004101	Liver	Cirrhotic	beta-Alanine metabolism	18/2530	31/8465	1.00e-03	5.57e-03	3.43e-03	18
hsa0033011	Liver	Cirrhotic	Arginine and proline metabolism	25/2530	50/8465	2.18e-03	9.41e-03	5.80e-03	25
hsa0033021	Liver	HCC	Arginine and proline metabolism	33/4020	50/8465	6.28e-03	1.77e-02	9.83e-03	33
hsa004102	Liver	HCC	beta-Alanine metabolism	22/4020	31/8465	6.93e-03	1.92e-02	1.07e-02	22
hsa0033031	Liver	HCC	Arginine and proline metabolism	33/4020	50/8465	6.28e-03	1.77e-02	9.83e-03	33
hsa004103	Liver	HCC	beta-Alanine metabolism	22/4020	31/8465	6.93e-03	1.92e-02	1.07e-02	22
hsa0033010	Oral cavity	OSCC	Arginine and proline metabolism	30/3704	50/8465	1.50e-02	3.26e-02	1.66e-02	30
hsa0033013	Oral cavity	OSCC	Arginine and proline metabolism	30/3704	50/8465	1.50e-02	3.26e-02	1.66e-02	30
hsa0033023	Oral cavity	LP	Arginine and proline metabolism	26/2418	50/8465	3.94e-04	2.08e-03	1.34e-03	26
hsa0033033	Oral cavity	LP	Arginine and proline metabolism	26/2418	50/8465	3.94e-04	2.08e-03	1.34e-03	26

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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

CNDP2

SNV

Missense_Mutation

novel

c.655N>C

p.Glu219Gln

p.E219Q

Q96KP4

protein_coding

tolerated(0.09)

possibly_damaging(0.709)

TCGA-A8-A06Q-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

CNDP2

SNV

Missense_Mutation

novel

c.362N>C

p.Arg121Pro

p.R121P

Q96KP4

protein_coding

tolerated(0.05)

benign(0.05)

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CNDP2

SNV

Missense_Mutation

rs764351246

c.958N>A

p.Glu320Lys

p.E320K

Q96KP4

protein_coding

deleterious(0)

possibly_damaging(0.797)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CNDP2

SNV

Missense_Mutation

novel

c.276G>C

p.Lys92Asn

p.K92N

Q96KP4

protein_coding

deleterious(0.02)

benign(0.02)

TCGA-AO-A0J9-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

CNDP2

SNV

Missense_Mutation

rs751626393

c.227N>T

p.Pro76Leu

p.P76L

Q96KP4

protein_coding

deleterious(0.02)

benign(0.304)

TCGA-E9-A1RB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

methotrexate

CNDP2

insertion

Nonsense_Mutation

novel

c.360_361insTACAAGAAAGTAAGAAAGTAAATCTTAATTAGTGACT

p.Arg121TyrfsTer7

p.R121Yfs*7

Q96KP4

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CNDP2

insertion

Nonsense_Mutation

novel

c.1287_1288insTGTGGATGATGCCGCGCAGGGCCCTTCGCACGTCTG

p.Gly429_Lys430insCysGlyTerCysArgAlaGlyProPheAlaArgLeu

p.G429_K430insCG*CRAGPFARL

Q96KP4

protein_coding

TCGA-AN-A0AR-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CNDP2

SNV

Missense_Mutation

rs146492497

c.809N>T

p.Thr270Met

p.T270M

Q96KP4

protein_coding

deleterious(0.01)

possibly_damaging(0.713)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CNDP2

SNV

Missense_Mutation

c.1345G>A

p.Glu449Lys

p.E449K

Q96KP4

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-DS-A0VM-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CNDP2

SNV

Missense_Mutation

c.1416G>T

p.Gln472His

p.Q472H

Q96KP4

protein_coding

tolerated(0.06)

benign(0)

TCGA-AA-3663-01

Colorectum

colon adenocarcinoma

Male

<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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