title: Long non-coding RNA HOTAIR is an independent prognostic marker of metastasis in estrogen receptor-positive primary breast cancer.
abstract: Expression of HOX transcript antisense intergenic RNA (HOTAIR)--a long non-coding RNA--has been examined in a variety of human cancers, and overexpression of HOTAIR is correlated with poor survival among breast, colon, and liver cancer patients. In this retrospective study, we examine HOTAIR expression in 164 primary breast tumors, from patients who do not receive adjuvant treatment, in a design that is paired with respect to the traditional prognostic markers. We show that HOTAIR expression differs between patients with or without a metastatic endpoint, respectively. Survival analysis shows that high HOTAIR expression in primary tumors is significantly associated with worse prognosis independent of prognostic markers (P = 0.012, hazard ratio (HR) 1.747). This association is even stronger when looking only at estrogen receptor (ER)-positive tumor samples (P = 0.0086, HR 1.985). In ER-negative tumor samples, we are not able to detect a prognostic value of HOTAIR expression, probably due to the limited sample size. These results are successfully validated in an independent dataset with similar associations (P = 0.018, HR 1.825). In conclusion, our findings suggest that HOTAIR expression may serve as an independent biomarker for the prediction of the risk of metastasis in ER-positive breast cancer patients.
authors.affiliation: Department of Clinical Genetics, Odense University Hospital, Sdr. Boulevard 29, 5000, Odense C, Denmark, kristina.sorensen1@rsyd.dk.
authors.forename: Kristina P
authors.initials: KP
authors.lastname: Sørensen
authors.forename: Mads
authors.initials: M
authors.lastname: Thomassen
authors.forename: Qihua
authors.initials: Q
authors.lastname: Tan
authors.forename: Martin
authors.initials: M
authors.lastname: Bak
authors.forename: Søren
authors.initials: S
authors.lastname: Cold
authors.forename: Mark
authors.initials: M
authors.lastname: Burton
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Larsen
authors.forename: Torben A
authors.initials: TA
authors.lastname: Kruse
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000235:genetics*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; C561566:HOTAIR long untranslated RNA, human; D062085:RNA, Long Noncoding; D011960:Receptors, Estrogen