Authors' Affiliations: Department of Surgery, Kyushu University Beppu Hospital, Beppu; Department of Surgery, Iwate Medical University, Morioka; Department of Gastric Surgery Division, National Cancer Center Hospital; Department of Medical Genome Sciences, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa-shi, Chiba; Department of Surgery, Teikyo University School of Medicine, Tokyo; Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka, University, Suita; and Department of Digestive Surgery, Hyogo Medical College, Japan.
Clin Cancer Res. 2013 Dec 1;19(23):6438-49. doi: 10.1158/1078-0432.CCR-12-3186. Epub 2013 Oct 4.
Recent studies revealed that both disseminated tumor cells and noncancerous cells contributed to cancer progression cooperatively in the bone marrow. Here, RNA-seq analysis of bone marrow from gastric cancer patients was performed to identify prognostic markers for gastric cancer.
Bone marrow samples from eight gastric cancer patients (stages I and IV: n = 4 each) were used for RNA-seq analysis. Results were validated through quantitative real-time PCR (qRT-PCR) analysis of HIST1H3D expression in 175 bone marrow, 92 peripheral blood, and 115 primary tumor samples from gastric cancer patients. miR-760 expression was assayed using qRT-PCR in 105 bone marrow and 96 primary tumor samples. Luciferase reporter assays were performed to confirm whether histone mRNAs were direct targets of miR-760. miR-760 expression was also evaluated in noncancerous cells from gastric cancer patients.
RNA-seq analysis of bone marrow samples from gastric cancer patients revealed higher expression of multiple histone mRNAs in stage IV patients. HIST1H3D expression in the bone marrow, peripheral blood, and primary tumor of stage IV patients was higher than that in stage I patients (P = 0.0284, 0.0243, and 0.0006, respectively). In contrast, miR-760 was downregulated in the bone marrow and primary tumor of stage IV patients compared with stage I patients (P = 0.0094 and 0.0018, respectively). Histone mRNA and miR-760 interacted directly. Furthermore, miR-760 was downregulated in noncancerous mucosa in stage IV gastric cancer patients.
Histone mRNA was upregulated, whereas miR-760 was downregulated in the bone marrow and primary tumor of advanced gastric cancer patients, suggesting that the histone mRNA/miR-760 axis had a crucial role in the development of gastric cancer.
最近的研究表明，在骨髓中，播散的肿瘤细胞和非癌细胞共同促进肿瘤的进展。在这里，对胃癌患者的骨髓进行了 RNA-seq 分析，以确定胃癌的预后标志物。
使用来自 8 名胃癌患者（I 期和 IV 期：n = 4 各）的骨髓样本进行 RNA-seq 分析。通过对 175 例胃癌患者的骨髓、92 例外周血和 115 例原发性肿瘤样本中 HIST1H3D 表达的定量实时 PCR（qRT-PCR）分析，对结果进行了验证。使用 qRT-PCR 测定了 105 例骨髓和 96 例原发性肿瘤样本中 miR-760 的表达。进行荧光素酶报告基因测定以确认组蛋白 mRNAs 是否为 miR-760 的直接靶标。还评估了来自胃癌患者的非癌细胞中的 miR-760 表达。
对胃癌患者骨髓样本的 RNA-seq 分析显示，IV 期患者中多个组蛋白 mRNA 的表达较高。IV 期患者的骨髓、外周血和原发性肿瘤中的 HIST1H3D 表达均高于 I 期患者（P = 0.0284、0.0243 和 0.0006）。相比之下，IV 期患者的骨髓和原发性肿瘤中的 miR-760 表达低于 I 期患者（P = 0.0094 和 0.0018）。组蛋白 mRNA 和 miR-760 直接相互作用。此外，IV 期胃癌患者的非癌性黏膜中 miR-760 下调。
在晚期胃癌患者的骨髓和原发性肿瘤中，组蛋白 mRNA 上调，而 miR-760 下调，表明组蛋白 mRNA/miR-760 轴在胃癌的发生发展中具有重要作用。
