Abstract
BackgroundMicroRNA-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.MethodsThe 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 χ2 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.ResultsmiR-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 (rs = −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).ConclusionsHigh 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.
Highlights
A rapidly growing number of treatment modalities have become available for the treatment of patients with breast cancer, which remarkably improve patient survival
Some endothelial-specific miRNAs have been implicated in the regulation of various aspects of angiogenesis, including the proliferation, migration and morphogenesis of endothelial cells, all of which are related to cancer cell metastasis [3]
Dysregulation of miRNA expression has been found in various types of human cancers, including cancers occurring in the breast, colon, and lung, chronic lymphocytic leukemia and malignant glioma [4,5,6,7,8]
Summary
A rapidly growing number of treatment modalities have become available for the treatment of patients with breast cancer, which remarkably improve patient survival. Tumor invasion and metastasis contribute to the great majority of breast cancer deaths. Increasing evidence supports a pivotal role for miRNAs in the multiple processes of carcinogenesis, including cell growth, apoptosis, differentiation, invasion and angiogenesis of tumor blood vessels [1,2]. Some endothelial-specific miRNAs have been implicated in the regulation of various aspects of angiogenesis, including the proliferation, migration and morphogenesis of endothelial cells, all of which are related to cancer cell metastasis [3]. 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
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