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
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.
Oncol Rep. 2016 Oct;36(4):2375-81. doi: 10.3892/or.2016.5021. Epub 2016 Aug 12.
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.
胰胆管癌是一种致命性很高的癌症。由于缺乏典型的临床症状及其解剖位置,胰胆管癌的检测较为困难。因此,发现生物标志物对于早期检测胰胆管癌很重要。一项研究表明,胰腺癌患者血清外泌体中miR-1246、miR-3976、miR-4306和miR-4644的表达水平高于健康对照参与者。假设唾液中的微小RNA(miRNA)表达谱与血清中的相似,唾液外泌体中的四种miRNA(miR-1246、miR-3976、miR-4306和miR-4644)也可能有助于胰胆管癌的检测。在本研究中,检测了这些miRNA是否可作为胰胆管癌的生物标志物。分别将12例胰胆管癌患者和13名健康对照参与者作为癌症组和对照组进行分析。收集未刺激的全唾液,分离唾液外泌体,并提取总RNA。使用定量实时PCR(RT-qPCR),癌症组中miR-1246和miR-4644的相对表达率显著高于对照组。构建受试者工作特征(ROC)曲线以分析这些miRNA的鉴别能力。对于miR-1246,结果得出曲线下面积(AUC)为0.814(P = 0.008)。对于miR-4644,结果得出AUC为0.763(P = 0.026)。对于miR-1246和miR-4644的组合,结果得出AUC增加至0.833(P = 0.005)。这项初步研究表明,唾液外泌体中的miR-1246和miR-4644可能是胰胆管癌的候选生物标志物。