Abstract:
PURPOSE:Early treatment of pancreatic ductal adenocarcinoma (PDAC) is significantly delayed due to the lack of liquid biopsy markers for early diagnosis at surgically resectable tumor stages. Recent studies suggest that microRNA-205 (miR-205) is involved in PDAC progression by post-transcriptional regulation of epithelial-to-mesenchymal transition (EMT). However, the clinical potential of miR-205 as diagnostic and prognostic marker remains undefined and its exact role in PDAC is still ambiguous. This retrospective study is a substantial contribution to this on-going scientific discussion. METHODS:Expression analysis of miR-205 and its molecular targets in PDAC cell lines (n = 5), human tissue (n = 73), and blood serum samples (n = 85) by qRT-PCR, tissue microarray immunohistochemistry, and western blot. Descriptive and explorative statistical analysis of miR-205's clinical potential for diagnosis and prognosis of PDAC. RESULTS:The expression of miR-205 differs more than 2000-fold (p < 0.001) between epithelial and mesenchymal-like human PDAC cell lines correlating with EMT-marker expression of E-cadherin, vimentin, fibronectin, and ZEB-1. Expression of miR-205 is significantly upregulated in carcinoma tissue (eightfold, p = 0.028) and serum (2.3-fold, p = 0.023) of PDAC patients compared to age-matched healthy controls. In our patient collective circulating miR-205 in combination with CA.19-9 outperforms the diagnostic accuracy of CA.19-9 alone with an AUC of 0.890 (p < 0.001), sensitivity of 0.867, and specificity of 0.933. Though non-significant, low expression of circulating miR-205 is more frequent in advanced tumor stages combined with a worse overall survival (6.9 vs. 11.9 months, p = 0.176). CONCLUSION:Besides its controversial role in carcinogenesis, miR-205 shows high potential as a solid and liquid biopsy marker in PDAC. This result is an urgent call for larger confirmatory multi-center studies.
journal_name
J Cancer Res Clin Oncoljournal_title
Journal of cancer research and clinical oncologyauthors
Michael Traeger M,Rehkaemper J,Ullerich H,Steinestel K,Wardelmann E,Senninger N,Abdallah Dhayat Sdoi
10.1007/s00432-018-2755-9subject
Has Abstractpub_date
2018-12-01 00:00:00pages
2419-2431issue
12eissn
0171-5216issn
1432-1335pii
10.1007/s00432-018-2755-9journal_volume
144pub_type
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journal_title:Journal of cancer research and clinical oncology
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journal_title:Journal of cancer research and clinical oncology
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journal_title:Journal of cancer research and clinical oncology
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journal_title:Journal of cancer research and clinical oncology
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journal_title:Journal of cancer research and clinical oncology
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journal_title:Journal of cancer research and clinical oncology
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journal_title:Journal of cancer research and clinical oncology
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journal_title:Journal of cancer research and clinical oncology
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journal_title:Journal of cancer research and clinical oncology
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doi:10.1007/BF01613135
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pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-003-0423-0
更新日期:2003-03-01 00:00:00
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journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-012-1204-4
更新日期:2012-08-01 00:00:00
abstract::The two hormone analogues octreotide and goserelin have been shown to decelerate growth of human pancreatic cancer in vitro and in vivo. The objective of this pilot study was to investigate the efficacy and toxicity of the combination of these two agents in patients with advanced pancreatic cancer. Octreotide was inje...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章,评审
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更新日期:1997-01-01 00:00:00
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pub_type: 杂志文章
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更新日期:2010-07-01 00:00:00
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journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF00410689
更新日期:1981-01-01 00:00:00
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journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF01613138
更新日期:1991-01-01 00:00:00
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journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
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更新日期:2006-01-01 00:00:00