长链非编码 RNA MEG3 多态性与乳腺癌新辅助化疗疗效的关系。
Association of LncRNA MEG3 polymorphisms with efficacy of neoadjuvant chemotherapy in breast cancer.
机构信息
Department of Breast Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Shanghai, 200127, People's Republic of China.
出版信息
BMC Cancer. 2019 Sep 5;19(1):877. doi: 10.1186/s12885-019-6077-3.
BACKGROUND
Breast cancer is the most common malignancy in women, and neoadjuvant chemotherapy has been recommended to the patients with locally advanced breast cancer as the initial treatments. Long non-coding RNA (lncRNA) MEG3, an identified tumor suppressor, has been implicated in the development of various cancers. However, there is no data to evaluate the effect of MEG3 polymorphisms on neoadjuvant treatment in the breast cancer.
METHODS
Genotyping was performed using Nanodispenser Spectro CHIP chip spotting and Mass ARRAY Compact System. Univariate and multivariate logistic regression analyses were used to analyze the associations between the MEG3 polymorphisms and the pathological complete response (pCR). The disease-free survival (DFS) was estimated by the Kaplan-Meier method, and multivariate Cox proportional hazards models were used to calculate the hazard ratios (HRs) with a 95% confidential interval (CI).
RESULTS
A total of 144 patients with available pretreatment blood species were enrolled in the SHPD002 clinic trial of neoadjuvant chemotherapy for breast cancer. MEG3 rs10132552 were significantly associated with good response (Adjusted OR = 2.79, 95% CI 1.096-7.103, p = 0.031) in dominant model. Median follow-up time was 20 months. In multiple regression analysis, rs10132552 TC + CC (adjusted HR = 0.127, 95% CI 0.22-0.728, p = 0.02) and rs941576 AG + GG (adjusted HR = 0.183, 95% CI 0.041-0.807, p = 0.025) were significantly associated with good DFS. MEG3 rs7158663 (OR = 0.377, 95% CI 0.155-0.917, p = 0.032) were associated with a low risk of hemoglobin decrease in dominant models.
CONCLUSIONS
LncRNA MEG3 polymorphisms were associated with the chemotherapy response and toxicity of paclitaxel and cisplatin. The result indicates that MEG3 polymorphisms can be considered as the predictive and prognostic markers for the breast cancer patients.
TRIAL REGISTRATION
Retrospectively registered (ClinicalTrials. Gov identifier: NCT02221999 ); date of registration: Aug 20th, 2014.
背景
乳腺癌是女性最常见的恶性肿瘤，局部晚期乳腺癌患者推荐新辅助化疗作为初始治疗。长链非编码 RNA（lncRNA）MEG3 是一种已被鉴定的肿瘤抑制因子，与多种癌症的发生有关。然而，尚无数据评估 MEG3 多态性对乳腺癌新辅助治疗的影响。
方法
采用 Nanodispenser Spectro CHIP 芯片点样和 Mass ARRAY Compact System 进行基因分型。采用单变量和多变量逻辑回归分析 MEG3 多态性与病理完全缓解（pCR）之间的关系。采用 Kaplan-Meier 法估计无病生存（DFS），采用多变量 Cox 比例风险模型计算 95%置信区间（CI）的风险比（HR）。
结果
共有 144 例可获得预处理血样的患者入组了新辅助化疗治疗乳腺癌的 SHPD002 临床试验。MEG3 rs10132552 在显性模型中与良好反应显著相关（调整后的 OR=2.79，95%CI 1.096-7.103，p=0.031）。中位随访时间为 20 个月。在多因素回归分析中，rs10132552 TC+CC（调整后的 HR=0.127，95%CI 0.22-0.728，p=0.02）和 rs941576 AG+GG（调整后的 HR=0.183，95%CI 0.041-0.807，p=0.025）与良好的 DFS 显著相关。MEG3 rs7158663（OR=0.377，95%CI 0.155-0.917，p=0.032）在显性模型中与血红蛋白降低的风险较低相关。
结论
lncRNA MEG3 多态性与紫杉醇和顺铂的化疗反应和毒性相关。结果表明，MEG3 多态性可作为乳腺癌患者的预测和预后标志物。
试验注册
回顾性注册（ClinicalTrials.gov 标识符：NCT02221999）；注册日期：2014 年 8 月 20 日。
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