Abstract
BackgroundBreast 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.MethodsGenotyping 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).ResultsA 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.ConclusionsLncRNA 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 registrationRetrospectively registered (ClinicalTrials. Gov identifier: NCT02221999); date of registration: Aug 20th, 2014.
Highlights
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
We found that maternally expressed gene3 (MEG3) was downregulated in the estrogen receptor (ER) positive breast cancer in our previous study [3]
MEG3 rs10132552 was significantly associated with tumor size in its recessive model (p = 0.022) and additive model (p = 0.007)
Summary
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. LncRNAs can regulate gene expression at epigenetic, transcriptional, and post-transcriptional levels, and can affect drug response and toxicity in cancer patients [1]. It was reported that some LncRNAs were tumor suppressor in breast cancer, such as growth arrest-specific 5, neuroblastoma associated transcript 1, and maternally expressed 3 (MEG3) [2]. Single nucleotide polymorphisms (SNPs) in MEG3 were reported to affect cell phenotypes and cause the risk of developing cancer [6] and the chemotherapy toxicity [7] in other cancers. There have been no analyses published to date of association between MEG3 and chemotherapy response in breast cancer patients
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