Published papers

Background: The aim of this study was to identify serum miRNAs that discriminate early gastric cancer (EGC) samples from non-cancer controls using a large cohort. Methods: This retrospective case–control study included 1417 serum samples from patients with EGC (seen at the National Cancer Center Hospital in Tokyo between 2008 and 2012) and 1417 age- and gender-matched non-cancer controls. The samples were randomly assigned to discovery and validation sets and the miRNA expression profiles of whole serum samples were comprehensively evaluated using a highly sensitive DNA chip (3D-Gene ) designed to detect 2565 miRNA sequences. Diagnostic models were constructed using the levels of several miRNAs in the discovery set, and the diagnostic performance of the model was evaluated in the validation set. Results: The discovery set consisted of 708 samples from EGC patients and 709 samples from non-cancer controls, and the validation set consisted of 709 samples from EGC patients and 708 samples from non-cancer controls. The diagnostic EGC index was constructed using four miRNAs (miR-4257, miR-6785-5p, miR-187-5p, and miR-5739). In the discovery set, a receiver operating characteristic curve analysis of the EGC index revealed that the area under the curve (AUC) was 0.996 with a sensitivity of 0.983 and a specificity of 0.977. In the validation set, the AUC for the EGC index was 0.998 with a sensitivity of 0.996 and a specificity of 0.953. Conclusions: A novel combination of four serum miRNAs could be a useful non-invasive diagnostic biomarker to detect EGC with high accuracy. A multicenter prospective study is ongoing to confirm the present observations. ®

79歳男。1ヵ月前より食欲低下、嚥下困難感を自覚し近医を受診、造影CTで多発転移性肝腫瘍、食道・胃透視検査で上部食道に5cmの陰影欠損を認め、著者らの施設で精査を予定していたが、意識障害が出現したため緊急入院となった。意識レベルはJCSII-10、腹部は平坦軟で圧痛なく、肝を正中に5cm触知された。また、Intact-PTHは正常であったが、PTHrPとCaの高値がみられ、血液検査で意識障害に肝性脳症と高Ca血症の関与が疑われた。そこで、肝不全用アミノ酸製剤、補液と利尿剤、エルシトニンが使用されたが入院6日目にCaは悪化して昏睡状態となり、ゾレドロン酸を投与するも意識状態および血清Caは改善せず肝不全も増悪、患者は入院8日目に死亡となった。尚、病理解剖では上部食道に28×44cm大、type 2病変を認め、食道内分泌細胞癌、小細胞型ほか、肝臓、肺、リンパ節への多発転移がみられ、肝臓はほぼ転移腫瘍で置換され、免疫組織化学染色で原発巣および転移巣でPTHrP産生が証明された。