Journal
ONCOTARGET
Volume 6, Issue 26, Pages 22114-22125Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.4294
Keywords
carcinoid; non-coding RNA; epigenetics; neuroendocrine tumor; rectum
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Funding
- Ono Cancer Research Foundation
- Takeda Science Foundation
- Sapporo Jikeikai Tomoiki Foundation
- Suhara Memorial Foundation
- Japanese Society of Gastroenterology Research Foundation
- Grants-in-Aid for Scientific Research [26640101, 25430115, 221S0001] Funding Source: KAKEN
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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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