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: DPP4

Gene summary for DPP4

Gene summary.

Gene information	Species	Human
	Gene symbol	DPP4
	Gene ID	1803
	Gene name	dipeptidyl peptidase 4
	Gene Alias	ADABP
	Cytomap	2q24.2
	Gene Type	protein-coding
	GO ID	GO:0001662
	UniProtAcc	P27487

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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
1803	DPP4	HCC1_Meng	Human	Liver	HCC	4.66e-44	1.19e-01	0.0246
1803	DPP4	HCC1	Human	Liver	HCC	3.99e-30	4.76e+00	0.5336
1803	DPP4	HCC2	Human	Liver	HCC	4.92e-27	4.42e+00	0.5341
1803	DPP4	Pt13.b	Human	Liver	HCC	7.74e-06	9.34e-02	0.0251
1803	DPP4	S014	Human	Liver	HCC	1.39e-38	1.44e+00	0.2254
1803	DPP4	S015	Human	Liver	HCC	8.55e-30	1.78e+00	0.2375
1803	DPP4	S016	Human	Liver	HCC	4.88e-41	1.61e+00	0.2243
1803	DPP4	S027	Human	Liver	HCC	4.46e-07	6.62e-01	0.2446
1803	DPP4	S028	Human	Liver	HCC	1.17e-32	1.04e+00	0.2503
1803	DPP4	S029	Human	Liver	HCC	7.41e-32	1.09e+00	0.2581
1803	DPP4	RNA-P25T1-P25T1-1	Human	Lung	AIS	1.17e-16	8.63e-01	-0.2116
1803	DPP4	RNA-P25T1-P25T1-2	Human	Lung	AIS	1.90e-06	9.17e-01	-0.1941
1803	DPP4	RNA-P25T1-P25T1-3	Human	Lung	AIS	3.89e-08	7.98e-01	-0.2107
1803	DPP4	RNA-P25T1-P25T1-4	Human	Lung	AIS	1.32e-15	7.99e-01	-0.2119
1803	DPP4	RNA-P6T2-P6T2-1	Human	Lung	IAC	2.11e-16	6.18e-01	-0.0166
1803	DPP4	RNA-P6T2-P6T2-2	Human	Lung	IAC	1.69e-22	6.59e-01	-0.0132
1803	DPP4	RNA-P6T2-P6T2-3	Human	Lung	IAC	2.63e-26	6.02e-01	-0.013
1803	DPP4	RNA-P6T2-P6T2-4	Human	Lung	IAC	2.24e-18	6.05e-01	-0.0121
1803	DPP4	RNA-P7T1-P7T1-2	Human	Lung	AIS	5.45e-06	5.70e-01	-0.0876
1803	DPP4	RNA-P7T1-P7T1-3	Human	Lung	AIS	9.39e-03	4.76e-01	-0.0822

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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
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:0060326	Stomach	GC	cell chemotaxis	35/1159	310/18723	4.34e-04	6.46e-03	35
GO:00362936	Stomach	GC	response to decreased oxygen levels	36/1159	322/18723	4.36e-04	6.47e-03	36
GO:00428863	Stomach	GC	amide transport	34/1159	301/18723	5.16e-04	7.28e-03	34
GO:00016666	Stomach	GC	response to hypoxia	34/1159	307/18723	7.34e-04	9.54e-03	34
GO:00704826	Stomach	GC	response to oxygen levels	37/1159	347/18723	8.94e-04	1.10e-02	37
GO:0071622	Stomach	GC	regulation of granulocyte chemotaxis	10/1159	51/18723	9.90e-04	1.18e-02	10
GO:00300735	Stomach	GC	insulin secretion	24/1159	195/18723	1.01e-03	1.20e-02	24
GO:0002688	Stomach	GC	regulation of leukocyte chemotaxis	17/1159	122/18723	1.38e-03	1.52e-02	17
GO:0090022	Stomach	GC	regulation of neutrophil chemotaxis	7/1159	32/18723	2.93e-03	2.65e-02	7
GO:1902622	Stomach	GC	regulation of neutrophil migration	8/1159	41/18723	3.22e-03	2.84e-02	8
GO:00224116	Stomach	GC	cellular component disassembly	42/1159	443/18723	3.99e-03	3.35e-02	42
GO:00027903	Stomach	GC	peptide secretion	26/1159	242/18723	4.39e-03	3.60e-02	26
GO:00016675	Stomach	GC	ameboidal-type cell migration	44/1159	475/18723	4.97e-03	3.96e-02	44
GO:00300723	Stomach	GC	peptide hormone secretion	25/1159	236/18723	6.15e-03	4.64e-02	25
GO:00507965	Stomach	GC	regulation of insulin secretion	19/1159	165/18723	6.67e-03	4.86e-02	19
GO:0016032113	Thyroid	PTC	viral process	236/5968	415/18723	2.48e-26	8.24e-24	236
GO:0022411113	Thyroid	PTC	cellular component disassembly	232/5968	443/18723	1.36e-19	1.75e-17	232
GO:0019058113	Thyroid	PTC	viral life cycle	167/5968	317/18723	8.87e-15	5.89e-13	167
GO:0044403113	Thyroid	PTC	biological process involved in symbiotic interaction	151/5968	290/18723	5.83e-13	2.85e-11	151
GO:0051701113	Thyroid	PTC	biological process involved in interaction with host	109/5968	203/18723	8.64e-11	2.99e-09	109

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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

DPP4

SNV

Missense_Mutation

novel

c.1444N>A

p.Leu482Ile

p.L482I

P27487

protein_coding

deleterious(0.05)

benign(0.258)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DPP4

SNV

Missense_Mutation

rs755540270

c.1051N>G

p.Thr351Ala

p.T351A

P27487

protein_coding

deleterious(0.02)

benign(0.112)

TCGA-AR-A2LK-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

anastrozole

DPP4

SNV

Missense_Mutation

c.1394N>T

p.Ala465Val

p.A465V

P27487

protein_coding

deleterious(0.01)

possibly_damaging(0.675)

TCGA-B6-A0IB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

DPP4

SNV

Missense_Mutation

c.2222N>A

p.Gly741Glu

p.G741E

P27487

protein_coding

deleterious(0)

probably_damaging(0.953)

TCGA-B6-A0X1-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

DPP4

SNV

Missense_Mutation

c.779N>C

p.Gly260Ala

p.G260A

P27487

protein_coding

deleterious(0.01)

probably_damaging(0.928)

TCGA-BH-A0DX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

DPP4

SNV

Missense_Mutation

novel

c.1493N>T

p.Ser498Leu

p.S498L

P27487

protein_coding

tolerated(0.13)

benign(0.007)

TCGA-BH-A2L8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

DPP4

SNV

Missense_Mutation

rs752793888

c.1067N>A

p.Arg356Lys

p.R356K

P27487

protein_coding

tolerated(0.52)

benign(0.084)

TCGA-C8-A26Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DPP4

SNV

Missense_Mutation

c.67N>A

p.Val23Met

p.V23M

P27487

protein_coding

tolerated(0.16)

probably_damaging(0.988)

TCGA-D8-A1XM-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

DPP4

deletion

Frame_Shift_Del

rs779957190

c.135_138delAACT

p.Thr46IlefsTer3

p.T46Ifs*3

P27487

protein_coding

TCGA-A2-A3XW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamyicin

DPP4

SNV

Missense_Mutation

c.2072N>C

p.Arg691Thr

p.R691T

P27487

protein_coding

deleterious(0)

probably_damaging(0.95)

TCGA-DG-A2KK-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

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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
1803	DPP4	PROTEASE, CELL SURFACE, DRUGGABLE GENOME, ENZYME	inhibitor	CHEMBL2105762	OMARIGLIPTIN
1803	DPP4	PROTEASE, CELL SURFACE, DRUGGABLE GENOME, ENZYME		VILDAGLIPTIN	VILDAGLIPTIN
1803	DPP4	PROTEASE, CELL SURFACE, DRUGGABLE GENOME, ENZYME		Beta-phe compound 2
1803	DPP4	PROTEASE, CELL SURFACE, DRUGGABLE GENOME, ENZYME		Imidazo cyclohexylamine derivative 3
1803	DPP4	PROTEASE, CELL SURFACE, DRUGGABLE GENOME, ENZYME		Peptide analog 47
1803	DPP4	PROTEASE, CELL SURFACE, DRUGGABLE GENOME, ENZYME		ENALAPRIL	ENALAPRIL	16678199
1803	DPP4	PROTEASE, CELL SURFACE, DRUGGABLE GENOME, ENZYME		Dutogliptin	DUTOGLIPTIN
1803	DPP4	PROTEASE, CELL SURFACE, DRUGGABLE GENOME, ENZYME	inhibitor	CHEMBL3833357	BEGELOMAB
1803	DPP4	PROTEASE, CELL SURFACE, DRUGGABLE GENOME, ENZYME	inhibitor	363894186	TALABOSTAT
1803	DPP4	PROTEASE, CELL SURFACE, DRUGGABLE GENOME, ENZYME		PMID25482888-Compound-52

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