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miR-27 作为乳腺癌进展和患者生存的预后标志物。

MiR-27 as a prognostic marker for breast cancer progression and patient survival.

机构信息

Department of Breast Surgery, Sun Yat-Sen Memorial Hospital, Sun-Yat-Sen University, Guangzhou, People's Republic of China.

出版信息

PLoS One. 2012;7(12):e51702. doi: 10.1371/journal.pone.0051702. Epub 2012 Dec 11.

Abstract

BACKGROUND

MicroRNA-27a (miR-27a) is thought to be an onco-microRNA that promotes tumor growth and metastasis by downregulating ZBTB10. The potential predictive value of miR-27a was studied in breast cancer patients.

METHODS

The expression of miR-27a and ZBTB10 was examined in 102 breast cancer cases using in situ hybridization (ISH) and immunohistochemistry techniques and were evaluated semi-quantitatively by examining the staining index. The Correlation of miR-27a and ZBTB10 expression was analyed by Spearman Rank Correlation. The association of miR-27a and ZBTB10 expression with clinicopathological characteristics was analyzed using the χ(2) test, and their effects on patient survival were analyzed by a log-rank test and the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were used to evaluate the prognostic values of miR-27a and ZBTB10.

RESULTS

miR-27a was markedly up-regulated in invasive breast cancers that expressed low levels of ZBTB10 (P<0.001). A reverse correlation between miR-27a and ZBTB10 was also observed in breast cancer tissue samples (r(s) = -0.478, P<0.001). Furthermore, the expression of miR-27a and ZBTB10 was significantly correlated with clinicopathological parameters, including tumor size, lymph node metastasis and distant metastasis (P<0.05), but not with receptor status. Patients with high miR-27a or low ZBTB10 expression tended to have significantly shorter disease-free survival times (57 months and 53 months, respectively, P <0.001) and overall survival times (58 months and 55 months, respectively, P <0.001). Univariate and multivariate analysis showed that both miR-27a and ZBTB10 were independent prognostic factors of disease-free survival in breast cancer patients (P <0.001), while only miR-27a was an independent predictor of overall survival (P <0.001).

CONCLUSIONS

High miR-27a expression is associated with poor overall survival in patients with breast cancer, which suggests that miR-27a could be a valuable marker of breast cancer progression.

摘要

背景

MicroRNA-27a(miR-27a)被认为是一种致癌microRNA,通过下调 ZBTB10 促进肿瘤生长和转移。本研究旨在探讨 miR-27a 在乳腺癌患者中的预测价值。

方法

采用原位杂交(ISH)和免疫组织化学技术检测 102 例乳腺癌组织中 miR-27a 和 ZBTB10 的表达,并通过染色指数进行半定量评估。采用 Spearman 秩相关分析 miR-27a 和 ZBTB10 表达的相关性。采用卡方检验分析 miR-27a 和 ZBTB10 表达与临床病理特征的关系,采用 log-rank 检验和 Kaplan-Meier 法分析其对患者生存的影响。采用单因素和多因素 Cox 回归分析评估 miR-27a 和 ZBTB10 的预后价值。

结果

miR-27a 在表达低水平 ZBTB10 的浸润性乳腺癌中显著上调(P<0.001)。在乳腺癌组织样本中也观察到 miR-27a 和 ZBTB10 之间存在负相关(r(s)=-0.478,P<0.001)。此外,miR-27a 和 ZBTB10 的表达与肿瘤大小、淋巴结转移和远处转移等临床病理参数显著相关(P<0.05),但与受体状态无关。miR-27a 高表达或 ZBTB10 低表达的患者无病生存时间(分别为 57 个月和 53 个月,P<0.001)和总生存时间(分别为 58 个月和 55 个月,P<0.001)均显著缩短。单因素和多因素分析显示,miR-27a 和 ZBTB10 均是乳腺癌患者无病生存的独立预后因素(P<0.001),而只有 miR-27a 是总生存的独立预测因素(P<0.001)。

结论

miR-27a 高表达与乳腺癌患者总生存不良相关,提示 miR-27a 可能是乳腺癌进展的有价值标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23d8/3519894/5f15e78202ba/pone.0051702.g001.jpg

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