Department of Anatomy, Physiology and Genetics, and Institute for Molecular Medicine, Uniformed Services University School of Medicine (USUHS), Bethesda, MD, United States of America.
Institute for Pathology, University Hospital Basel, Basel, Switzerland.
PLoS One. 2018 Oct 15;13(10):e0205837. doi: 10.1371/journal.pone.0205837. eCollection 2018.
Annexin A7 (ANXA7) is a member of the multifunctional calcium or phospholipid-binding annexin gene family. While low levels of ANXA7 are associated with aggressive types of cancer, the clinical impact of ANXA7 in prostate cancer remains unclear. Tissue microarrays (TMA) have revealed several new molecular markers in human tumors. Herein, we have identified the prognostic impact of ANXA7 in a prostate cancer using a tissue microarray containing 637 different specimens.
The patients were diagnosed with prostate cancer and long-term follow-up information on progression (median 5.3 years), tumor-specific and overall survival data (median 5.9 years) were available. Expression of Ki67, Bcl-2, p53, CD-10 (neutral endopeptidase), syndecan-1 (CD-138) and ANXA7 were analyzed by immunohistochemistry.
A bimodal distribution of ANXA7 was observed. Tumors expressing either high or no ANXA7 were found to be associated with poor prognosis. However, ANXA7 at an optimal level, in between high and no ANXA7 expression, had a better prognosis. This correlated with low Ki67, Bcl-2, p53 and high syndecan-1 which are known predictors of early recurrence. At Gleason grade 3, ANXA7 is an independent predictor of poor overall survival with a p-value of 0.003. Neoadjuvant hormonal therapy, which is known to be associated with overexpression of Bcl-2 and inhibition of Ki67 LI and CD-10, was found to be associated with under-expression of ANXA7.
The results of this TMA study identified ANXA7 as a new prognostic factor and indicates a bimodal correlation to tumor progression.
膜联蛋白 A7(ANXA7)是多功能钙或磷脂结合膜联蛋白基因家族的成员。虽然低水平的 ANXA7 与侵袭性癌症类型相关,但 ANXA7 在前列腺癌中的临床影响尚不清楚。组织微阵列(TMA)已经在人类肿瘤中揭示了几种新的分子标志物。在此,我们使用包含 637 个不同标本的组织微阵列来确定 ANXA7 在前列腺癌中的预后影响。
这些患者被诊断为前列腺癌,并且有进展(中位随访时间为 5.3 年)、肿瘤特异性和总生存数据(中位随访时间为 5.9 年)的长期随访信息。通过免疫组织化学分析 Ki67、Bcl-2、p53、CD-10(中性内肽酶)、 syndecan-1(CD-138)和 ANXA7 的表达。
观察到 ANXA7 的双峰分布。表达高或无 ANXA7 的肿瘤与预后不良相关。然而,在高和无 ANXA7 表达之间处于最佳水平的 ANXA7 具有更好的预后。这与已知预测早期复发的低 Ki67、Bcl-2、p53 和高 syndecan-1 相关。在 Gleason 分级 3 中,ANXA7 是总生存的独立预后因素,p 值为 0.003。已知与 Bcl-2 过表达和 Ki67 LI 和 CD-10 抑制相关的新辅助激素治疗与 ANXA7 的低表达相关。
这项 TMA 研究的结果确定 ANXA7 为新的预后因素,并表明与肿瘤进展呈双峰相关。