Circulating HOTAIR expression predicts the clinical response to neoadjuvant chemotherapy in patients with breast cancer

Cancer Biomark. 2018;22(2):249-256. doi: 10.3233/CBM-170874.

Abstract

Background: Long noncoding RNA HOTAIR has been detected in the serum of patients with various malignances and may be served as novel biomarker for diagnosis and prognosis prediction of breast cancer. However, the value of circulating HOTAIR to predict the response to neoadjuvant chemotherapy (NAC) remains unclear.

Objective: In the present study, we analyzed whether pretreatment circulating HOTAIR levels predict the response to NAC and investigated prognostic impact of circulating HOTAIR on disease-free survival (DFS) in breast cancer patients treated with NAC.

Methods: Circulating HOTAIR levels in the serum of 112 breast cancer patients before NAC were measured using quantitative real-time PCR. The correlation of circulating HOTAIR with the clinicopathologic status and the response to NAC were analyzed. Kaplan-Meier survival analysis and log-rank test were used to estimate the DFS.

Results: In 112 serum samples obtained before NAC, high circulating HOTAIR was associated with larger tumor size, more positive lymph nodes as well as more distant metastasis. However, there was no significant correlation between the circulating HOTAIR levels and age, Ki67 status or hormone receptor. Furthermore, patients with high circulating HOTAIR achieved less clinical response as well as pathologic complete response than those with low circulating HOTAIR (p< 0.05). The Kaplan-Meier survival curve with a median follow-up of 48 months demonstrated that patients with high circulating HOTAIR expression had a worse disease-free survival than those with low circulating HOTAIR (log-rank p= 0.012).

Conclusions: High circulating HOTAIR level correlates with less response to neoadjuvant chemotherapy as well as a worse prognosis in breast cancer patients. Therefore, the present study provides a favorable basis to use circulating HOTAIR as a predictor of neoadjuvant chemotherapy response.

Keywords: Circulating HOTAIR; breast cancer; neoadjuvant chemotherapy.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers
  • Breast Neoplasms / blood*
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / therapy
  • Cell-Free Nucleic Acids*
  • Combined Modality Therapy
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Prognosis
  • RNA, Long Noncoding / blood
  • RNA, Long Noncoding / genetics*
  • Recurrence
  • Survival Analysis
  • Treatment Outcome

Substances

  • Biomarkers
  • Cell-Free Nucleic Acids
  • HOTAIR long untranslated RNA, human
  • RNA, Long Noncoding