title: Circulating DNA of HOTAIR in serum is a novel biomarker for breast cancer.
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 finding was confirmed at the validation stage. Though circulating MALAT-1 DNA was altered in the discovery stage, it showed no significant 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 specificity of 68.3 %. Moreover, a correlation between the DNA level of circulating HOTAIR and the progress of breast cancer was established. We have demonstrated that the circulating DNA of HOTAIR is a potential biomarker for breast cancer.
authors.affiliation: Institute of Molecular Medicine, Peking University, 5 Yiheyuan Rd., Beijing, 100871, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institute of Molecular Medicine, Peking University, 5 Yiheyuan Rd., Beijing, 100871, China.
authors.forename: Xinyun
authors.initials: X
authors.lastname: Song
authors.affiliation: Institute of Molecular Medicine, Peking University, 5 Yiheyuan Rd., Beijing, 100871, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research, Breast Center, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: Yuntao
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Division of Prevention and Community Health, National Center for Cardiovascular Diseases, Beijing Fuwai Hospital, Beijing, China.
authors.forename: Zengwu
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research, Breast Center, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Laboratory Medicine, The Affiliated Hospital of Yanbian University, Yanji, China.
authors.forename: Xin
authors.initials: X
authors.lastname: You
authors.affiliation: Institute of Molecular Medicine, Peking University, 5 Yiheyuan Rd., Beijing, 100871, China. liangz@pku.edu.cn.
authors.forename: Zicai
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Institute of Molecular Medicine, Peking University, 5 Yiheyuan Rd., Beijing, 100871, China. caohuiqing@pku.edu.cn.
authors.forename: Huiqing
authors.identifier: http://orcid.org/0000-0001-9728-6743
authors.initials: H
authors.lastname: Cao
mesh_terms: D000328:Adult; D000368:Aged; D017398:Alternative Splicing; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000097:blood / Q000235:genetics*; D012372:ROC Curve
chemical_list: D014408:Biomarkers, Tumor; C561566:HOTAIR long untranslated RNA, human; D062085:RNA, Long Noncoding