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: 8.72). 06/2011; 17(17):5812-21. DOI: 10.1158/1078-0432.CCR-11-0695
Source: PubMed


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.

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    • "Thus, high expressors of this triple miRNA combination (miR-21/23a/27a) may be identified as having a much worse prognosis and may benefit from anti-miRNA therapy, although the best way to deliver such a treatment and potential off-target effects are unknown. Another recent study demonstrated that miR-10b might be a novel diagnostic and predictive biomarker for PDAC [146]. MiR-10b is indeed overexpressed in PDAC patients and reduced expression of miR-10b was associated with improved response to multimodality neoadjuvant therapy, likelihood of surgical resection, delayed time to metastasis, and increased survival [146]. "
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    • "Recent studies illustrate the role of miRNAs on the regulation of gene expression and proteins in metastasis. For example, it has been shown that miR-10b, which is up-regulated by EMT transcription factor Twist, is associated with increased invasiveness and metastatic potential (35, 36). Furthermore, it was shown that the miR-200 family (miR-200a, miR-200b, miR-200c, miR-141, and miR-429) and miR-205 play critical roles in regulating EMT by directly targeting the mRNAs encoding E-cadherin repressors Zeb1 and Zeb2 (37). "
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    • "Although purely exploratory in nature, due to the relatively low number of subjects analysed, our data support the prognostic value of miR-10b (Additional file 1: Figure S6), in line with available evidence regarding the role played by this microRNA in cancer biology, according to both preclinical [32,34,39-41] and clinical models [34,41-43]. miR-10b over-expression has been associated not only with enhanced aggressiveness of malignant cells in a variety of experimental models [32,34,39-41,44,45], but also with worse prognosis in patients with breast [34,43] and pancreatic carcinoma [41,42]. "
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