MicroRNA-10b Expression Correlates with Response to Neoadjuvant Therapy and Survival in Pancreatic Ductal Adenocarcinoma

Department of Medicine and Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, USA.
Clinical Cancer Research (Impact Factor: 8.19). 06/2011; 17(17):5812-21. DOI: 10.1158/1078-0432.CCR-11-0695
Source: PubMed

ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy. Diagnosis and management of PDAC are hampered by the absence of sensitive and specific disease biomarkers. MicroRNAs (miRNA) are noncoding regulatory RNAs involved in initiation and progression of human cancers. In this study, we sought to determine whether miR-10b could serve as a biomarker for PDAC.
miRNA expression was characterized by fluorescence-based in situ hybridization using locked nucleic acid-modified DNA probes against miR-10b, miR-21, miR-155, miR-196a, and miR-210, followed by codetection of proteins by immunohistochemistry on the same tissue sections. miRNA expression in surgically resected PDAC tissues and in endoscopic ultrasonography (EUS)-guided fine-needle aspirate (EUS-FNA) samples was analyzed in cytokeratin 19 (CK19)-positive epithelial cells using optical intensity analysis.
In 10 resected PDAC samples, miR-10b was the most frequently and consistently overexpressed miRNA among characterized miRNAs, exhibiting a four-fold increase in the cancer cells (P = 0.012). Given this preferential overexpression of miR-10b, we sought to determine whether miR-10b expression was clinically relevant. Accordingly, miR-10b expression was examined in 106 EUS-FNA samples obtained from pancreatic lesions. miR-10b expression was increased in cancer cells compared with CK19-positive epithelial cells in benign lesions (P = 0.0001). In patients with PDACs, lower levels of miR-10b were associated with improved response to multimodality neoadjuvant therapy, likelihood of surgical resection, delayed time to metastasis, and increased survival.
miR-10b is a novel diagnostic biomarker for PDACs when assessing pancreatic lesions. Expression of miR-10b is predictive of response to neoadjuvant therapy and outcome in this disease.

Download full-text


Available from: Stuart Gordon, Jul 04, 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: microRNA-10b (miR-10b) expression in pancreatic ductal adenocarcinoma (PDAC), as identified by in situ hybridization, is highly correlated with cancer diagnosis, therapy response, and prognosis. If these findings are further confirmed in prospective studies, miR-10b could be used to improve the management of PDAC and decrease the mortality rate of this deadly cancer.
    Clinical Cancer Research 08/2011; 17(17):5527-9. DOI:10.1158/1078-0432.CCR-11-1477 · 8.19 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The promise of personalized medicine is highly dependent on the identification of biomarkers that inform diagnostic decisions and treatment options, as well as on the accurate, rapid and cost-effective detection and interpretation of these biomarkers. miRNAs, which are short noncoding regulatory RNAs, are rapidly emerging as a novel class of biomarkers with a unique set of biological and chemical properties that makes them very appealing candidates for theranostic applications in cancer. Since the utility of some protein-encoding gene biomarkers is already exploited in routine clinical practice, it will be important to identify areas in which miRNAs provide complementary or superior information to these existing (and other translational) biomarkers to enhance the diagnostic, prognostic and predictive power of molecular characterization of tumors. In this article, the challenges and opportunities for integration of miRNA-based assays in the clinical toolkit to improve care and management of patients afflicted with solid tumors will be discussed.
    Expert Review of Molecular Diagnostics 11/2011; 11(8):813-27. DOI:10.1586/erm.11.69 · 4.27 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: microRNAs (miRs) are a recently recognized class of noncoding short RNAs, 17-25 nucleotides in length, that play a role in post-transcriptional gene regulation by translational repression and/or mRNA degradation. Various miRs have been highlighted in pancreatic cancer development and metastasis, and as potential clinical diagnostic/prognostic biomarkers. Recently, studies have indicated that miRs are responsible for resistance to chemotherapeutic agents. The miR-10b has been identified as a 'metastamiR' in various tumor types, notably breast cancer, but data surrounding its relevance in pancreatic ductal adenocarcinoma has been sparse. The evaluated article presents data indicating that miR-10b is upregulated in pancreatic ductal adenocarcinoma and can be used as a diagnostic marker in endoscopic ultrasound-guided fine-needle aspiration biopsies of suspicious pancreatic lesions. In addition, miR-10b may be able to guide neoadjuvant gemcitabine-based chemoradiotherapy and predict metastatic-free survival and overall survival.
    Expert Review of Anticancer Therapy 12/2011; 11(12):1837-42. DOI:10.1586/era.11.184 · 3.06 Impact Factor