Zeng Zhihao, Chen Xiaowu, Zhu Dajian, Luo Zhongran, Yang Min
Department of Cardiothoracic Surgery, ShunDe Hospital of Southern Medical University, Foshan, China.
Department of General Surgery, ShunDe Hospital of Southern Medical University, Foshan, China.
Yonsei Med J. 2017 Jul;58(4):697-702. doi: 10.3349/ymj.2017.58.4.697.
The microRNA-34 (miR-34) family is important in tumor regulation. This study aimed to investigate the association of circulating miR-34 family proteins with clinicopathological features and their prognostic value in triple-negative breast cancer (TNBC) patients.
In this cohort study, 173 TNBC patients admitted to First People's Hospital of Shunde from May 1, 2009 to April 30, 2013 were enrolled. Meanwhile, 75 age-matched healthy women volunteers were identified as healthy controls (HCs). We examined the expression of miR-34 family (miR-34a/b/c) proteins in plasma collected from TNBC patients before any treatment was performed and from age-matched HCs using qPCR methods.
The expressions of miR-34a/34b/34c were significantly lower in TNBC patients than in HC (p<0.001, p=0.027, p<0.001, respectively). miR-34a was correlated with tumor grade (p=0.038), lymph node positive (p=0.027), distant metastasis (p=0.004), and surgery (p=0.023); miR-34b was correlated with lymph node positivity (p=0.027); and miR-34c was correlated with tumor grade (p=0.017) and distant metastasis (p<0.001). Kaplan-Meier curve analysis displayed low expression of miR-34a as associated with worse overall survival (OS) (p=0.011), as well as miR-34c low expression (p=0.002). In addition, univariate and multivariate Cox proportional hazards regression was performed, and low expression of miR-34c (p=0.011) was found to be an independent risk factor for OS, as well as tumor grade (p=0.013), lymph node positive (p=0.050), and distant metastasis (p=0.021).
In conclusion, this study demonstrated reduced miR-34a/c expression is highly associated with tumor progression and indicated worse prognosis. Also, miR-34c was an independent risk factor for OS in TNBC patients.
微小RNA-34(miR-34)家族在肿瘤调控中起重要作用。本研究旨在探讨循环miR-34家族蛋白与三阴性乳腺癌(TNBC)患者临床病理特征的相关性及其预后价值。
在这项队列研究中,纳入了2009年5月1日至2013年4月30日在顺德区第一人民医院收治的173例TNBC患者。同时,75名年龄匹配的健康女性志愿者被确定为健康对照(HC)。我们使用qPCR方法检测了在进行任何治疗之前从TNBC患者以及年龄匹配的HC收集的血浆中miR-34家族(miR-34a/b/c)蛋白的表达。
TNBC患者中miR-34a/34b/34c的表达明显低于HC(分别为p<0.001、p=0.027、p<0.001)。miR-34a与肿瘤分级(p=0.038)、淋巴结阳性(p=0.027)、远处转移(p=0.004)和手术(p=0.023)相关;miR-34b与淋巴结阳性(p=0.027)相关;miR-34c与肿瘤分级(p=0.017)和远处转移(p<0.001)相关。Kaplan-Meier曲线分析显示,miR-34a低表达与较差的总生存期(OS)相关(p=0.011),miR-34c低表达也相关(p=0.002)。此外,进行了单因素和多因素Cox比例风险回归分析,发现miR-34c低表达(p=0.011)是OS的独立危险因素,还有肿瘤分级(p=0.013)、淋巴结阳性(p=0.050)和远处转移(p=0.021)。
总之,本研究表明miR-34a/c表达降低与肿瘤进展高度相关,并提示预后较差。此外,miR-34c是TNBC患者OS的独立危险因素。