microRNA-10b Expression Correlates with Response to Neoadjuvant Therapy and Survival in Pancreatic Ductal Adenocarcinoma
Menée sur 106 échantillons tumoraux, cette étude montre que l'expression du micro-ARN 10b est associée à la réponse à un traitement néo-adjuvant et à la survie de patients atteints d'un adénocarcinome canalaire du pancréas
Introduction: 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 are non-coding 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. Methods: miRNA expression was characterized by fluorescence-based in situ hybridization (ISH) using Locked Nucleic Acid (LNA)-modified DNA probes against miR-10b, miR-21, miR-155 , miR-196a, and miR-210, followed by co-detection 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. Results: In 10 resected PDAC samples miR-10b was the most frequently and consistently overexpressed miRNA among characterized miRNAs, exhibiting a 4-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 to CK19-positive epithelial cells in benign lesions (p=0.0001). In patients with PDAC, 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. Conclusion: miR-10b is a novel diagnostic biomarker for PDAC when assessing pancreatic lesions. Expression of miR-10b is predictive of response to neoadjuvant therapy and outcome in this disease.
Clinical Cancer Research , résumé, 2011