Dipeptidyl peptidase like 6 promoter methylation is a potential prognostic biomarker for pancreatic ductal adenocarcinoma
© 2020 The Author(s)..
BACKGROUND: Hypermethylation of gene promoters plays an important role in tumorigenesis. The present study aimed to identify and validate promoter methylation-driven genes (PMDGs) for pancreatic ductal adenocarcinoma (PDAC).
METHODS: Based on GSE49149 and the PDAC cohort of The Cancer Genome Atlas (TCGA), differential analyses of promoter methylation, correlation analysis, and Cox regression analysis were performed to identify PMDGs. The promoter methylation level was assessed by bisulfite sequencing polymerase chain reaction (BSP) in paired tumor and normal tissues of 72 PDAC patients. Kaplan-Meier survival analyses were performed to evaluate the clinical value of PMDGs.
RESULTS: In GSE49149, the β-value of the dipeptidyl peptidase like 6 (DPP6) promoter was significantly higher in tumor compared with normal samples (0.50 vs. 0.24, P<0.001). In the PDAC cohort of TCGA, the methylation level of the DPP6 promoter was negatively correlated with mRNA expression (r = -0.54, P<0.001). In a multivariate Cox regression analysis, hypermethylation of the DPP6 promoter was an independent risk factor for PDAC (hazard ratio (HR) = 543.91, P=0.002). The results of BSP revealed that the number of methylated CG sites in the DPP6 promoter was greater in tumor samples than in normal samples (7.43 vs. 2.78, P<0.001). The methylation level of the DPP6 promoter was moderately effective at distinguishing tumor from normal samples (area under ROC curve (AUC) = 0.74, P<0.001). Hypermethylation of the DPP6 promoter was associated with poor overall (HR = 3.61, P<0.001) and disease-free (HR = 2.01, P=0.016) survivals for PDAC patients.
CONCLUSION: These results indicate that DPP6 promoter methylation is a potential prognostic biomarker for PDAC.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:40 |
|---|---|
| Enthalten in: |
Bioscience reports - 40(2020), 7 vom: 31. Juli |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Zhao, Xin [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 15.04.2021 Date Revised 15.04.2021 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1042/BSR20200214 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM31277219X |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM31277219X | ||
| 003 | DE-627 | ||
| 005 | 20231225145131.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1042/BSR20200214 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1042.xml |
| 035 | |a (DE-627)NLM31277219X | ||
| 035 | |a (NLM)32701143 | ||
| 035 | |a (PII)BSR20200214 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Zhao, Xin |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Dipeptidyl peptidase like 6 promoter methylation is a potential prognostic biomarker for pancreatic ductal adenocarcinoma |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 15.04.2021 | ||
| 500 | |a Date Revised 15.04.2021 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2020 The Author(s). | ||
| 520 | |a BACKGROUND: Hypermethylation of gene promoters plays an important role in tumorigenesis. The present study aimed to identify and validate promoter methylation-driven genes (PMDGs) for pancreatic ductal adenocarcinoma (PDAC) | ||
| 520 | |a METHODS: Based on GSE49149 and the PDAC cohort of The Cancer Genome Atlas (TCGA), differential analyses of promoter methylation, correlation analysis, and Cox regression analysis were performed to identify PMDGs. The promoter methylation level was assessed by bisulfite sequencing polymerase chain reaction (BSP) in paired tumor and normal tissues of 72 PDAC patients. Kaplan-Meier survival analyses were performed to evaluate the clinical value of PMDGs | ||
| 520 | |a RESULTS: In GSE49149, the β-value of the dipeptidyl peptidase like 6 (DPP6) promoter was significantly higher in tumor compared with normal samples (0.50 vs. 0.24, P<0.001). In the PDAC cohort of TCGA, the methylation level of the DPP6 promoter was negatively correlated with mRNA expression (r = -0.54, P<0.001). In a multivariate Cox regression analysis, hypermethylation of the DPP6 promoter was an independent risk factor for PDAC (hazard ratio (HR) = 543.91, P=0.002). The results of BSP revealed that the number of methylated CG sites in the DPP6 promoter was greater in tumor samples than in normal samples (7.43 vs. 2.78, P<0.001). The methylation level of the DPP6 promoter was moderately effective at distinguishing tumor from normal samples (area under ROC curve (AUC) = 0.74, P<0.001). Hypermethylation of the DPP6 promoter was associated with poor overall (HR = 3.61, P<0.001) and disease-free (HR = 2.01, P=0.016) survivals for PDAC patients | ||
| 520 | |a CONCLUSION: These results indicate that DPP6 promoter methylation is a potential prognostic biomarker for PDAC | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a TCGA | |
| 650 | 4 | |a methylation | |
| 650 | 4 | |a pancreatic ductal adenocarcinoma | |
| 650 | 4 | |a promoter | |
| 650 | 7 | |a Biomarkers, Tumor |2 NLM | |
| 650 | 7 | |a Nerve Tissue Proteins |2 NLM | |
| 650 | 7 | |a Potassium Channels |2 NLM | |
| 650 | 7 | |a DPP6 protein, human |2 NLM | |
| 650 | 7 | |a EC 3.4.- |2 NLM | |
| 650 | 7 | |a Dipeptidyl-Peptidases and Tripeptidyl-Peptidases |2 NLM | |
| 650 | 7 | |a EC 3.4.14.- |2 NLM | |
| 700 | 1 | |a Cao, Di |e verfasserin |4 aut | |
| 700 | 1 | |a Ren, Zhangyong |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Zhe |e verfasserin |4 aut | |
| 700 | 1 | |a Lv, Shaocheng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Jiqiao |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Lixin |e verfasserin |4 aut | |
| 700 | 1 | |a Lang, Ren |e verfasserin |4 aut | |
| 700 | 1 | |a He, Qiang |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Bioscience reports |d 1981 |g 40(2020), 7 vom: 31. Juli |w (DE-627)NLM01264465X |x 1573-4935 |7 nnns |
| 773 | 1 | 8 | |g volume:40 |g year:2020 |g number:7 |g day:31 |g month:07 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1042/BSR20200214 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 40 |j 2020 |e 7 |b 31 |c 07 | ||