Analysis of the molecular features of rectal carcinoid tumors to identify new biomarkers that predict biological malignancy
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Kei Mitsuhashi1,*, Itaru Yamamoto1,*, Hiroyoshi Kurihara1,*, Shinichi Kanno1,*, Miki Ito1, Hisayoshi Igarashi1, Keisuke Ishigami1, Yasutaka Sukawa1,2, Mami Tachibana1, Hiroaki Takahashi3, Takashi Tokino4, Reo Maruyama5, Hiromu Suzuki5, Kohzoh Imai6, Yasuhisa Shinomura1, Hiroyuki Yamamoto7,†, Katsuhiko Nosho1,†
1Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan
2Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
3Department of Gastroenterology, Keiyukai Daini Hospital, Sapporo, Japan
4Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
5Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo, Japan
6The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
7Department of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kawasaki, Japan
*These authors have contributed equally to this work
†These authors have contributed equally to this work
Katsuhiko Nosho, e-mail: firstname.lastname@example.org
Keywords: carcinoid, non-coding RNA, epigenetics, neuroendocrine tumor, rectum
Received: April 1, 2015 Accepted: June 5, 2015 Published: June 17, 2015
Although gastrointestinal carcinoid tumors are relatively rare in the digestive tract, a quarter of them are present in the rectum. In the absence of specific tumor biomarkers, lymphatic or vascular invasion is generally used to predict the risk of lymph node metastasis. We, therefore, examined the genetic and epigenetic alterations potentially associated with lymphovascular invasion among 56 patients with rectal carcinoid tumors. We also conducted a microRNA (miRNA) array analysis. Our analysis failed to detect mutations in BRAF, KRAS, NRAS, or PIK3CA or any microsatellite instability (MSI); however, we did observe CpG island methylator phenotype (CIMP) positivity in 13% (7/56) of the carcinoid tumors. The CIMP-positive status was significantly correlated with lymphovascular invasion (P = 0.036). The array analysis revealed that microRNA-885 (miR-885)-5p was the most up-regulated miRNA in the carcinoid tumors with lymphovascular invasion compared with that in those without invasion. In addition, high miR-885-5p expression was independently associated with lymphovascular invasion (P = 0.0002). In conclusion, our findings suggest that miR-885-5p and CIMP status may be useful biomarkers for predicting biological malignancy in patients with rectal carcinoid tumors.
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