Zhuge B-Z, Du B-R, Meng X-L, Zhang Y-Q
Clinical Laboratory, Linyi People's Hospital, Linyi, Shandong, China.
Eur Rev Med Pharmacol Sci. 2017 May;21(10):2413-2420.
In this study, we aimed to explore prognostic value of MASTL (microtubule-associated serine/threonine kinase-like) in breast cancer patients on the basis of ER status and molecular subtypes.
The raw microarray data (GDS5666) of 4T1 derived bone-aggressive explant and primary tumor explant were reanalyzed to identify the dysregulated genes. To pool previous annotated genomic data that assessed the association between MASTL expression and metastatic relapse (MR) risk, MR-free survival, any event (AE, defined as any relapse or death) risk, and AE-free survival in breast cancer patients, a meta-analysis was performed by bc-GenExMiner 4.0.
MASTL is a significantly upregulated gene in 4T1 bone-aggressive explant compared to primary tumor explant. Univariate Cox analysis showed that high MASTL expression is associated with a higher risk of MR (HR: 1.43, 95%CI: 1.28-1.60; p<0.001) and a higher risk of AE (HR: 1.27, 95%CI: 1.18-1.37; p<0.001) in ER+ breast cancer. Also, high MASTL expression also predicts a worse MR-free survival (HR: 1.74, 95%CI: 1.40-2.17; p<0.001) and a worse AE-free survival (HR: 1.42, 95%CI: 1.23-1.63; p<0.001) in ER+ breast cancer. However, the associations were not observed in ER- patients. The following NPI adjusted analyses confirmed the results of univariate Cox analysis. In Single Sample Predictors (SSPs) and Subtype Clustering Models (SCMs) subtypes, high MASTL expression is associated with increased risk of AE and predicts a poor AE-free survival in ER+ subgroups.
MASTL might be a valuable indicator of MR risk and AE risk in ER+ patients, but not in ER- patients.
在本研究中，我们旨在基于雌激素受体（ER）状态和分子亚型探讨微管相关丝氨酸/苏氨酸激酶样蛋白（MASTL）在乳腺癌患者中的预后价值。
重新分析4T1来源的骨侵袭性外植体和原发性肿瘤外植体的原始微阵列数据（GDS5666），以鉴定失调基因。为汇总先前评估MASTL表达与乳腺癌患者转移复发（MR）风险、无MR生存期、任何事件（AE，定义为任何复发或死亡）风险以及无AE生存期之间关联的注释基因组数据，使用bc-GenExMiner 4.0进行荟萃分析。
与原发性肿瘤外植体相比，MASTL在4T1骨侵袭性外植体中是一个显著上调的基因。单变量Cox分析显示，在ER阳性乳腺癌中，MASTL高表达与更高的MR风险（风险比：1.43，95%置信区间：1.28 - 1.60；p<0.001）和更高的AE风险（风险比：1.27，95%置信区间：1.18 - 1.37；p<0.001）相关。此外，在ER阳性乳腺癌中，MASTL高表达还预示着更差的无MR生存期（风险比：1.74，95%置信区间：1.40 - 2.17；p<0.001）和更差的无AE生存期（风险比：1.42，95%置信区间：1.23 - 1.63；p<0.001）。然而，在ER阴性患者中未观察到这些关联。以下NPI调整分析证实了单变量Cox分析的结果。在单样本预测器（SSP）和亚型聚类模型（SCM）亚型中MASTL高表达与ER阳性亚组中AE风险增加相关，并预示着较差的无AE生存期。
MASTL可能是ER阳性患者MR风险和AE风险的有价值指标，但不是ER阴性患者的。
