Circulating DNA of HOTAIR in serum is a novel biomarker for breast cancer

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Web End = Breast Cancer Res Treat (2015) 152:199208 DOI 10.1007/s10549-015-3431-2

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Web End = Circulating DNA of HOTAIR in serum is a novel biomarker for breast cancer

Lei Zhang1 Xinyun Song1 Xiaoxia Wang1 Yuntao Xie2 Zengwu Wang3

Ye Xu2 Xin You4 Zicai Liang1 Huiqing Cao1

Received: 16 January 2015 / Accepted: 18 May 2015 / Published online: 2 June 2015 Springer Science+Business Media New York 2015

Abstract Long non-coding HOX transcript antisense intergenic RNA (HOTAIR) plays an important role in breast cancer. The purpose of this study was to determine whether circulating HOTAIR can be used for breast cancer diagnosis. HOTAIR in serum was measured by PCR-based direct detection. Reverse transcriptase and DNase I treatment were used to distinguish the DNA and RNA forms of HOTAIR. To determine whether circulating HOTAIR is a biomarker for breast cancer, the DNA of HOTAIR from breast cancer patients and healthy controls was measured at both the discovery stage (48 individuals) and an independent validation stage (156 individuals). The diagnostic

accuracy was assessed by the receiver operating characteristic curve (ROC) and the area under the curve (AUC). We showed that the major form of HOTAIR-derived fragment in serum is DNA rather than RNA in our study, the same as for MALAT-1, another well-described lincRNA. A higher circulating DNA level of HOTAIR was found in patients at the discovery stage (P = 0.0008). ROC analysis revealed that the circulating HOTAIR DNA distinguished breast cancer patients from healthy individuals (AUC = 0.799). This nding was conrmed at the validation stage. Though circulating MALAT-1 DNA was altered in the discovery stage, it showed no signicant difference in the validation stage. In the entire set of 204 samples, the circulating HOTAIR DNA showed a 2.15-fold change in patients compared with healthy controls (P \ 0.0001, AUC = 0.786). The optimal cutoff value for diagnosis was 0.30 with sensitivity of 80.0 % and specicity of 68.3 %. Moreover, a correlation between the DNA level of circulating HOTAIR and the progress of breast cancer was established. We have...