循环 HOTAIR 表达预测乳腺癌患者新辅助化疗的临床反应。

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

机构信息

Department of Breast Surgery, The First Affiliated Hospital of Jinan University, Jinan University, Tianhe District, Guangzhou, Guangdong, China.

Department of Reproductive Medical Center, Guangdong Women and Children Hospital, Panyu District, Guangzhou, Guangdong, China.

出版信息

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

DOI:10.3233/CBM-170874

PMID:29630518

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.

摘要

背景

长链非编码 RNA HOTAIR 已在各种恶性肿瘤患者的血清中被检测到，可能作为乳腺癌诊断和预后预测的新型生物标志物。然而，循环 HOTAIR 预测新辅助化疗（NAC）反应的价值尚不清楚。

目的

本研究旨在分析术前循环 HOTAIR 水平是否可预测 NAC 反应，并探讨循环 HOTAIR 对接受 NAC 治疗的乳腺癌患者无病生存（DFS）的预后影响。

方法

采用实时定量 PCR 检测 112 例 NAC 前乳腺癌患者血清中循环 HOTAIR 水平，分析循环 HOTAIR 与临床病理状态及 NAC 反应的相关性。Kaplan-Meier 生存分析和对数秩检验用于估计 DFS。

结果

在 NAC 前获得的 112 份血清样本中，高循环 HOTAIR 与肿瘤较大、更多阳性淋巴结和远处转移有关。然而，循环 HOTAIR 水平与年龄、Ki67 状态或激素受体之间无显著相关性。此外，与低循环 HOTAIR 相比，高循环 HOTAIR 患者的临床缓解率和病理完全缓解率较低（p<0.05）。中位随访 48 个月的 Kaplan-Meier 生存曲线表明，高循环 HOTAIR 表达的患者无病生存较差（log-rank p=0.012）。