Division of Endocrinology and Metabolic Bone Diseases, Department of Medicine III, Technische Universität Dresden, Dresden, Germany.
Center for Healthy Ageing Department of Medicine III, Technische Universität Dresden, Dresden, Germany.
Breast Cancer Res Treat. 2020 Apr;180(2):515-524. doi: 10.1007/s10549-020-05570-0. Epub 2020 Feb 10.
Periostin is a secreted extracellular matrix protein, which was originally described in osteoblasts. It supports osteoblastic differentiation and bone formation and has been implicated in the pathogenesis of several human malignancies, including breast cancer. However, little is known about the prognostic value of serum periostin levels in breast cancer.
In this study, we analyzed serum levels of periostin in a cohort of 509 primary, non-metastatic breast cancer patients. Disseminated tumor cell (DTC) status was determined using bone marrow aspirates obtained from the anterior iliac crests. Periostin levels were stratified according to several clinical parameters and Pearson correlation analyses were performed. Kaplan-Meier survival curves were assessed by using the log-rank (Mantel-Cox) test. To identify prognostic factors, multivariate Cox regression analyses were used.
Mean serum levels of periostin were 505 ± 179 pmol/l. In older patients (> 60 years), periostin serum levels were significantly increased compared to younger patients (540 ± 184 pmol/l vs. 469 ± 167 pmol/l; p < 0.0001) and age was positively correlated with periostin expression (p < 0.0001). When stratifying the cohort according to periostin serum concentrations, the overall and breast cancer-specific mortality were significantly higher in those patients with high serum periostin (above median) compared to those with low periostin during a mean follow-up of 8.5 years (17.7% vs. 11.4% breast cancer-specific death; p = 0.03; hazard ratio 1.65). Periostin was confirmed to be an independent prognostic marker for breast cancer-specific survival (p = 0.017; hazard ratio 1.79). No significant differences in serum periostin were observed when stratifying the patients according to their DTC status.
Our findings emphasize the relevance of periostin in breast cancer and reveal serum periostin as a potential marker for disease prediction, independent on the presence of micrometastases.
骨膜蛋白是一种分泌型细胞外基质蛋白，最初在成骨细胞中描述。它支持成骨细胞分化和骨形成，并与几种人类恶性肿瘤的发病机制有关，包括乳腺癌。然而，关于乳腺癌患者血清骨膜蛋白水平的预后价值知之甚少。
在这项研究中，我们分析了 509 例原发性非转移性乳腺癌患者的血清骨膜蛋白水平。使用从前髂嵴获得的骨髓抽吸物确定播散性肿瘤细胞 (DTC) 状态。根据几个临床参数对骨膜蛋白水平进行分层，并进行 Pearson 相关性分析。通过对数秩（Mantel-Cox）检验评估 Kaplan-Meier 生存曲线。为了确定预后因素，使用多变量 Cox 回归分析。
骨膜蛋白的平均血清水平为 505±179 pmol/l。在年龄较大的患者（>60 岁）中，骨膜蛋白血清水平明显高于年龄较小的患者（540±184 pmol/l 比 469±167 pmol/l；p<0.0001），并且年龄与骨膜蛋白表达呈正相关（p<0.0001）。当根据骨膜蛋白血清浓度对队列进行分层时，在平均 8.5 年的随访期间，那些血清骨膜蛋白水平较高（高于中位数）的患者的总死亡率和乳腺癌特异性死亡率明显高于那些血清骨膜蛋白水平较低的患者（17.7%比 11.4%的乳腺癌特异性死亡；p=0.03；风险比 1.65）。骨膜蛋白被证实是乳腺癌特异性生存的独立预后标志物（p=0.017；风险比 1.79）。当根据患者的 DTC 状态对患者进行分层时，血清骨膜蛋白没有观察到显著差异。
我们的研究结果强调了骨膜蛋白在乳腺癌中的相关性，并揭示了血清骨膜蛋白作为一种潜在的疾病预测标志物的潜力，与微转移的存在无关。
