miR‑1246 and miR‑4644 in salivary exosome as potential biomarkers for pancreatobiliary tract cancer

Machida,Tatsuya; Tomofuji,Takaaki; Maruyama,Takayuki; Yoneda,Toshiki; Ekuni,Daisuke; Azuma,Tetsuji; Miyai,Hisataka; Mizuno,Hirofumi; Kato,Hironari; Tsutsumi,Koichiro; Uchida,Daisuke; Takaki,Akinobu; Okada,Hiroyuki; Morita,Manabu

doi:10.3892/or.2016.5021

miR‑1246 and miR‑4644 in salivary exosome as potential biomarkers for pancreatobiliary tract cancer

Authors:
- Tatsuya Machida
- Takaaki Tomofuji
- Takayuki Maruyama
- Toshiki Yoneda
- Daisuke Ekuni
- Tetsuji Azuma
- Hisataka Miyai
- Hirofumi Mizuno
- Hironari Kato
- Koichiro Tsutsumi
- Daisuke Uchida
- Akinobu Takaki
- Hiroyuki Okada
- Manabu Morita
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Affiliations: Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700‑8558, Japan, Center of Innovative Clinical Medicine, Okayama University Hospital, Okayama 700‑8558, Japan, Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700‑8558, Japan
Published online on: August 12, 2016 https://doi.org/10.3892/or.2016.5021
Pages: 2375-2381

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Abstract

Pancreatobiliary tract cancer is a highly fatal cancer. Detection of pancreatobiliary tract cancer is difficult because it lacks typical clinical symptoms and because of its anatomical location. Biomarker discovery is therefore important to detect pancreatobiliary tract cancer in its early stage. A study demonstrated that expression levels of miR‑1246, miR‑3976, miR‑4306, and miR‑4644 in serum exosomes were higher in pancreatic cancer patients than these levels in healthy control participants. Supposing that microRNA (miRNA) expression profiles in saliva are similar to those in serum, four miRNAs (miR‑1246, miR‑3976, miR‑4306, and miR‑4644) in salivary exosomes may also be useful for detection of pancreatobiliary tract cancer. In this study, it was examined whether these miRNAs could be used as biomarkers for pancreatobiliary tract cancer. Twelve pancreatobiliary tract cancer patients and 13 healthy control participants were analyzed as a cancer and a control group, respectively. Unstimulated whole saliva was collected, salivary exosomes were isolated, and total RNA was extracted. Using quantitative real‑time PCR (RT‑qPCR), the relative expression ratios of miR‑1246 and miR‑4644 were significantly higher in the cancer group than these ratios in the control group. Receiver operating characteristic (ROC) curves were constructed to analyze the discrimination power of these miRNAs. For miR‑1246, the results yielded an area under the curve (AUC) of 0.814 (P=0.008). For miR‑4644, the results yielded an AUC of 0.763 (P=0.026). For the combination of miR‑1246 and miR‑4644, the results yielded an increased AUC of 0.833 (P=0.005). This pilot study suggests that miR‑1246 and miR‑4644 in salivary exosomes could be candidate biomarkers for pancreatobiliary tract cancer.

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