Chen Hui, Ren Chuanli, Han Chongxu, Wang Daxin, Chen Yong, Fu Deyuan
Geriatric Medicine, Northern Jiangsu People's Hospital and Clinical Medical College of Yangzhou University, Yangzhou, China.
Clinical Medical Testing Laboratory, Northern Jiangsu People's Hospital and Clinical Medical College of Yangzhou University, Yangzhou, China; Department of Epidemiology and Biostatistics, Ministry of Education (MOE) Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
PLoS One. 2015 Mar 20;10(3):e0119384. doi: 10.1371/journal.pone.0119384. eCollection 2015.
MicroRNA (miR)-486-5p expression is often reduced in human cancers. However, its expression in gastric carcinoma and its relation to clinicopathological features and prognosis are unclear. Tissue microarrays were constructed from 84 patients with gastric adenocarcinoma (GC) who were undergoing radical resection. miR-486-5p expression was detected by miRNA-locked nucleic acid in situ hybridization, and its correlations with clinicopathological features and overall survival were analyzed. Bioinformatic studies predict that fibroblast growth factor 9 (FGF9) is a potential target gene of miR-486-5p. miR-486-5p was mainly located in the cytoplasm of GC cells and neighboring normal tissues. Compared with paracancerous normal tissue, miR-486-5p expression was decreased in 63.1% (53/84) of the GC samples, increased in 32.1% (27/84) and unchanged in 4.8% (4/84). FGF9 expression was decreased in 69.0% (58/84) of GC samples and increased in 31.0% (26/84) compared with normal paracancerous tissues using immunohistochemical analysis. Low or unchanged miR-486-5p expression (P = 0.002), tumor stage (P = 0.001), tumor status (P = 0.001), node status (P = 0.001), tumor size (P = 0.004), and depth of tumor invasion (P = 0.013) were significant negative prognostic predictors for overall survival in patients with GC. After stratification according to American Joint Committee on Cancer (AJCC) stage, low/unchanged miR-486-5p expression remained a significant predictor of poor survival in stage II (P = 0.024) and stage III (P = 0.003). Cox regression analysis identified the following predictors of poor prognosis: tumor status (hazard ratio [HR], 7.19; 95% confidence interval [CI], 1.75-29.6; P = 0.006), stage (HR, 2.62; 95%CI, 1.50-4.59; P = 0.001), lymph node metastasis (HR, 2.52; 95% CI, 1.27-4.99; P = 0.008), low/unchanged miR-486-5p (HR, 2.47; 95% CI, 1.35-4.52; P = 0.003), high level of FGF9 (HR, 2.41; 95% CI, 1.42-4.09; P = 0.001) and tumor size (HR, 2.50; 95% CI, 1.30-4.82; P = 0.006). Low or unchanged expression of miR-486-5p compared with neighboring normal tissues was associated with a poor prognosis, while high expression was associated with a good prognosis in GC. miR-486-5p may thus be useful for evaluating prognosis and may provide a novel target treatment in patients with GC.
微小RNA（miR）-486-5p在人类癌症中的表达常常降低。然而，其在胃癌中的表达及其与临床病理特征和预后的关系尚不清楚。从84例接受根治性切除的胃腺癌（GC）患者中构建组织芯片。通过miRNA锁核酸原位杂交检测miR-486-5p的表达，并分析其与临床病理特征和总生存期的相关性。生物信息学研究预测成纤维细胞生长因子9（FGF9）是miR-486-5p的潜在靶基因。miR-486-5p主要位于GC细胞和邻近正常组织的细胞质中。与癌旁正常组织相比，63.1%（53/84）的GC样本中miR-486-5p表达降低，32.1%（27/84）升高，4.8%（4/84）不变。使用免疫组织化学分析，与正常癌旁组织相比，69.0%（58/84）的GC样本中FGF9表达降低，31.0%（26/84）升高。低或不变的miR-486-5p表达（P = 0.002）、肿瘤分期（P = 0.001）、肿瘤状态（P = 0.001）、淋巴结状态（P = 0.001）、肿瘤大小（P = 0.004）和肿瘤浸润深度（P = 0.013）是GC患者总生存期的显著负性预后预测指标。根据美国癌症联合委员会（AJCC）分期分层后，低/不变的miR-486-5p表达在II期（P = 0.024）和III期（P = 0.003）患者中仍然是生存不良的显著预测指标。Cox回归分析确定了以下预后不良的预测因素：肿瘤状态（风险比[HR]，7.19；95%置信区间[CI]，1.75-29.6；P = 0.006）、分期（HR，2.62；95%CI，1.50-4.59；P = 0.001）、淋巴结转移（HR，2.52；95%CI，1.27-4.99；P = 0.008）、低/不变的miR-486-5p（HR，2.47；95%CI，1.35-4.52；P = 0.003）、高水平的FGF9（HR，2.41；
