Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Breast Surgery, Affiliated Union Hospital, Fujian Medical University, Fuzhou, China.
Cancer Sci. 2018 Jul;109(7):2294-2301. doi: 10.1111/cas.13644. Epub 2018 Jun 27.
Breast cancer is one of the most common malignant diseases in women. Triple-negative breast cancer (TNBC) shows higher aggressiveness and recurrence rates than other subtypes, and there are no effective targets or tailored treatments for TNBC patients. Thus, finding effective prognostic markers for TNBC could help clinicians in their ability to care for their patients. We used tissue microarrays (TMAs) to detect microRNA-493 (miR-493) expression in breast cancer samples. A miRCURY LNA detection probe specific for miR-493 was used in in situ hybridization assays. Staining results were reviewed by two independent pathologists and classified as high or low expression of miR-493. Kaplan-Meier survival plots and multivariate Cox analysis were carried out to clarify the relationship between miR-493 and survival. In the Kaplan-Meier analysis, patients with high miR-493 expression had better disease-free survival than patients with low miR-493 expression. After adjusting for common clinicopathological factors in breast cancer, the expression level of miR-493 was still a significant prognostic factor in breast cancer. Further subtype analysis revealed that miR-493 expression levels were only significantly prognostic in TNBC patients. These results were validated in the Molecular Taxonomy of Breast Cancer International Consortium database for overall survival. We proved the prognostic role of miR-493 in TNBC by using one of the largest breast cancer TMAs available and validated it in a large public RNA sequencing database.
乳腺癌是女性最常见的恶性肿瘤之一。三阴性乳腺癌(TNBC)比其他亚型具有更高的侵袭性和复发率,并且没有针对 TNBC 患者的有效靶点或针对性治疗方法。因此,寻找有效的 TNBC 预后标志物可以帮助临床医生更好地照顾他们的患者。我们使用组织微阵列(TMA)检测乳腺癌样本中的 microRNA-493(miR-493)表达。使用针对 miR-493 的 miRCURY LNA 检测探针进行原位杂交检测。两位独立的病理学家对染色结果进行了回顾,并将其分类为 miR-493 的高或低表达。进行 Kaplan-Meier 生存图和多变量 Cox 分析以阐明 miR-493 与生存之间的关系。在 Kaplan-Meier 分析中,高 miR-493 表达的患者无病生存率优于低 miR-493 表达的患者。在调整乳腺癌常见临床病理因素后,miR-493 的表达水平仍然是乳腺癌的显著预后因素。进一步的亚组分析表明,miR-493 表达水平仅在 TNBC 患者中具有显著的预后意义。这些结果在乳腺癌国际联合会分子分类数据库中得到了总体生存的验证。我们通过使用最大的乳腺癌 TMA 之一来证明 miR-493 在 TNBC 中的预后作用,并在大型公共 RNA 测序数据库中进行了验证。