Yang Yinlong, Qian Jinxian, Xiang Youqun, Chen Yizuo, Qu Jinmiao
Department of Breast Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200000, People's Republic of China.
Department of Surgical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, People's Republic of China.
Oncotarget. 2017 Jan 24;8(4):6833-6844. doi: 10.18632/oncotarget.14304.
Although a few studies have assessed the prognostic value of long noncoding RNA HOTTIP in patients with malignant tumors, the relationship between HOTTIP and clinical outcome of breast cancer remains elusive. The aim of this study is to explore the prognostic significance of HOTTIP in breast cancer patients. A meta-analysis was performed to involve the eligible studies to investigate the association of HOTTIP expression level with outcome in cancer patients. Pooled hazard ratios (HRs) and 95% confidence interval (CI) of HOTTIP for cancer survival were calculated. Five relevant articles involving 460 patients with various solid carcinomas were included in this meta-analysis. For overall survival, high HOTTIP expression could significantly predict worse outcome with the pooled HR of 2.29 (95 % CI 1.72-3.03, P < 0.00001). Furthermore, Gene Expression Omnibus was performed to evaluate the association of HOTTIP expression with the prognosis in breast cancer patients. It was also found an indication that high HOTTIP expression was associated with worse survival in breast cancer patients by microarray analysis (GSE20711, GSE16446 and GSE9195). Finally, association between HOTTIP levels and clinicopathological factors and prognosis was also analyzed in an independent validation cohort including 100 breast cancer cases. HOTTIP expression was correlated with tumor size (P=0.025), lymph node status (P=0.009) and TNM stage (P=0.0001) in the breast cancer validation cohort. The Kaplan-Meier survival curves indicated that breast cancer patients with high HOTTIP expression had worse overall survival (P=0.0139) and disease-free survival (P=0.0003). Multivariate survival analysis based on the Cox proportional hazards model showed that HOTTP is considered as an independent prognostic factor in breast cancer patients. Together, our combined results suggest that high HOTTIP expression may be serving as an unfavorable prognosis predictor for breast cancer patients.
尽管有一些研究评估了长链非编码RNA HOTTIP在恶性肿瘤患者中的预后价值，但HOTTIP与乳腺癌临床结局之间的关系仍不清楚。本研究的目的是探讨HOTTIP在乳腺癌患者中的预后意义。进行了一项荟萃分析，纳入符合条件的研究，以调查HOTTIP表达水平与癌症患者结局之间的关联。计算了HOTTIP对癌症生存的合并风险比（HRs）和95%置信区间（CI）。本荟萃分析纳入了5篇涉及460例各种实体癌患者的相关文章。对于总生存期，HOTTIP高表达可显著预测更差的结局，合并HR为2.29（95%CI 1.72 - 3.03，P < 0.00001）。此外，利用基因表达综合数据库评估HOTTIP表达与乳腺癌患者预后的关联。通过微阵列分析（GSE20711、GSE16446和GSE9195）也发现有迹象表明HOTTIP高表达与乳腺癌患者较差的生存率相关。最后，在一个包括100例乳腺癌病例的独立验证队列中，分析了HOTTIP水平与临床病理因素及预后之间的关联。在乳腺癌验证队列中，HOTTIP表达与肿瘤大小（P = 0.025）、淋巴结状态（P = 0.009）和TNM分期（P = 0.0001）相关。Kaplan-Meier生存曲线表明，HOTTIP高表达的乳腺癌患者总生存期（P = 0.0139）和无病生存期（P = 0.0003）更差。基于Cox比例风险模型的多因素生存分析表明，HOTTP被认为是乳腺癌患者的独立预后因素。总之，我们的综合结果表明，HOTTIP高表达可能是乳腺癌患者不良预后的预测指标。
