Research Papers:

The prognostic value of long noncoding RNA HOTTIP on clinical outcomes in breast cancer

Yinlong Yang _, Jinxian Qian, Youqun Xiang, Yizuo Chen and Jinmiao Qu

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Oncotarget. 2017; 8:6833-6844. https://doi.org/10.18632/oncotarget.14304

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Yinlong Yang1,*, Jinxian Qian1,*, Youqun Xiang2, Yizuo Chen2, Jinmiao Qu2

1Department of Breast Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200000, People’s Republic of China

2Department of Surgical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, People’s Republic of China

*These authors have contributed equally to this work

Correspondence to:

Yinlong Yang, email: [email protected]

Jinmiao Qu, email: [email protected]

Keywords: long non-coding RNA, HOTTIP, prognosis, breast cancer

Received: October 31, 2016     Accepted: December 13, 2016     Published: December 27, 2016


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.

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