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Erschienen in: Tumor Biology 5/2013

01.10.2013 | Research Article

DLC-1 is a candidate biomarker methylated and down-regulated in pancreatic ductal adenocarcinoma

verfasst von: Yu-Zheng Xue, Tie-Long Wu, Yan-Min Wu, Ying-Yue Sheng, Zhe-Qiang Wei, Yu-Feng Lu, Li-Hua Yu, Jian-Ping Li, Zhao-Shen Li

Erschienen in: Tumor Biology | Ausgabe 5/2013

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Abstract

Pancreatic ductal adenocarcinoma (PDA) is one of the most aggressive malignancies in humans, and its prognosis is generally poor even after surgery. Many advances have been made to understand the pathogenesis of PDA; however, the molecular mechanisms that lead to pancreatic carcinogenesis are still not clearly understood. The aims of this study were to investigate the relationship between DLC-1 methylation status and clinicopathological characteristics of PDA patients and evaluate the role of DLC-1 methylation status in PDA. The expression of DLC-1 mRNA in PDA tissues was analyzed by real-time PCR. The methylation status of DLC-1 was analyzed by methylation-specific polymerase chain reaction (MSP). Furthermore, we determined the prognostic importance of DLC-1 methylation status in PDA patients. Our results showed that the expression level of DLC-1 mRNA in PDA tissues was lower than that in non-cancerous tissues. The rate of DLC-1 promoter methylation was significantly higher in PDA tissues than in adjacent non-cancerous tissues (p < 0.001). Downregulation of DLC-1 was strongly correlated with promoter methylation (P = 0.003). The presence of DLC-1 methylation in PDA tissue samples was significantly correlated with clinical stage (P = 0.005), histological differentiation (P = 0.05), and lymph node metastasis (P = 0.006). Kaplan–Meier survival analysis showed that DLC-1 methylation status was inversely correlated with overall survival of the PDA patients. Further, Cox multivariate analysis indicated that DLC-1 methylation status was an independent prognostic factor for the overall survival rate of PDA patients. In conclusion, our data suggest that downregulation of DLC-1 may be explained by DNA methylation; DLC-1 may be a biomarker for PDA.
Literatur
6.
10.
Zurück zum Zitat Ullmannova V, Popescu NC. Expression profile of the tumor suppressor genes DLC-1 and DLC-2 in solid tumors. Int J Oncol. 2006;29:1127–32.PubMed Ullmannova V, Popescu NC. Expression profile of the tumor suppressor genes DLC-1 and DLC-2 in solid tumors. Int J Oncol. 2006;29:1127–32.PubMed
11.
13.
Zurück zum Zitat Feng X, Li C, Liu W, Chen H, Zhou W, Wang L, et al. DLC-1, a candidate tumor suppressor gene, inhibits the proliferation, migration and tumorigenicity of human nasopharyngeal carcinoma cells. Int J Oncol. 2013;42:1973–84. doi:10.3892/ijo.2013.1885.PubMed Feng X, Li C, Liu W, Chen H, Zhou W, Wang L, et al. DLC-1, a candidate tumor suppressor gene, inhibits the proliferation, migration and tumorigenicity of human nasopharyngeal carcinoma cells. Int J Oncol. 2013;42:1973–84. doi:10.​3892/​ijo.​2013.​1885.PubMed
15.
Zurück zum Zitat Chen WT, Yang CH, Wu CC, Huang YC, Chai CY. Aberrant deleted in liver cancer-1 expression is associated with tumor metastasis and poor prognosis in urothelial carcinoma. APMIS. 2013. doi:10.1111/apm.12060. Chen WT, Yang CH, Wu CC, Huang YC, Chai CY. Aberrant deleted in liver cancer-1 expression is associated with tumor metastasis and poor prognosis in urothelial carcinoma. APMIS. 2013. doi:10.​1111/​apm.​12060.
16.
Zurück zum Zitat Peng H, Long F, Wu Z, Chu Y, Li J, Kuai R, Zhang J, Kang Z, Zhang X, Guan M. Downregulation of DLC-1 gene by promoter methylation during primary colorectal cancer progression. Biomed Res Int. 2013; 2013: 181384. doi:10.1155/2013/181384. Peng H, Long F, Wu Z, Chu Y, Li J, Kuai R, Zhang J, Kang Z, Zhang X, Guan M. Downregulation of DLC-1 gene by promoter methylation during primary colorectal cancer progression. Biomed Res Int. 2013; 2013: 181384. doi:10.​1155/​2013/​181384.
17.
Zurück zum Zitat Guan CN, Zhang PW, Lou HQ, Liao XH, Chen BY. DLC-1 expression levels in breast cancer assessed by qRT- PCR are negatively associated with malignancy. Asian Pac J Cancer Prev. 2012;13:1231–3.CrossRefPubMed Guan CN, Zhang PW, Lou HQ, Liao XH, Chen BY. DLC-1 expression levels in breast cancer assessed by qRT- PCR are negatively associated with malignancy. Asian Pac J Cancer Prev. 2012;13:1231–3.CrossRefPubMed
21.
Zurück zum Zitat Zhang T, Zheng J, Liu C, Lu Y. Expression of DLC-1 in clear cell renal cell carcinoma: prognostic significance for progression and metastasis. Urol Int. 2009;82:380–7. doi:10.1159/000218524.CrossRefPubMed Zhang T, Zheng J, Liu C, Lu Y. Expression of DLC-1 in clear cell renal cell carcinoma: prognostic significance for progression and metastasis. Urol Int. 2009;82:380–7. doi:10.​1159/​000218524.CrossRefPubMed
22.
Zurück zum Zitat Jin Z, Mori Y, Yang J, Sato F, Ito T, Cheng Y, et al. Hypermethylation of the nel-like 1 gene is a common and early event and is associated with poor prognosis in early-stage esophageal adenocarcinoma. Oncogene. 2007;26:6332–40. doi:10.1038/sj.onc.1210461.CrossRefPubMed Jin Z, Mori Y, Yang J, Sato F, Ito T, Cheng Y, et al. Hypermethylation of the nel-like 1 gene is a common and early event and is associated with poor prognosis in early-stage esophageal adenocarcinoma. Oncogene. 2007;26:6332–40. doi:10.​1038/​sj.​onc.​1210461.CrossRefPubMed
23.
Zurück zum Zitat Sun D, Zhang Z, Van do N, Huang G, Ernberg I, Hu L. Aberrant methylation of CDH13 gene in nasopharyngeal carcinoma could serve as a potential diagnostic biomarker. Oral Oncol. 2007;43:82–7.CrossRefPubMed Sun D, Zhang Z, Van do N, Huang G, Ernberg I, Hu L. Aberrant methylation of CDH13 gene in nasopharyngeal carcinoma could serve as a potential diagnostic biomarker. Oral Oncol. 2007;43:82–7.CrossRefPubMed
24.
Zurück zum Zitat Brock MV, Gou M, Akiyama Y, Muller A, Wu TT, Montgomery E, et al. Prognostic importance of promoter hypermethylation of multiple genes in esophageal adenocarcinoma. Clin Cancer Res. 2003;9:2912–9.PubMed Brock MV, Gou M, Akiyama Y, Muller A, Wu TT, Montgomery E, et al. Prognostic importance of promoter hypermethylation of multiple genes in esophageal adenocarcinoma. Clin Cancer Res. 2003;9:2912–9.PubMed
Metadaten
Titel
DLC-1 is a candidate biomarker methylated and down-regulated in pancreatic ductal adenocarcinoma
verfasst von
Yu-Zheng Xue
Tie-Long Wu
Yan-Min Wu
Ying-Yue Sheng
Zhe-Qiang Wei
Yu-Feng Lu
Li-Hua Yu
Jian-Ping Li
Zhao-Shen Li
Publikationsdatum
01.10.2013
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 5/2013
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-0846-4

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