Lokman Noor A, Pyragius Carmen E, Ruszkiewicz Andrew, Oehler Martin K, Ricciardelli Carmela
Discipline of Obstetrics and Gynaecology, School of Medicine, Robinson Research Institute, The University of Adelaide, Adelaide, South Australia, Australia; Adelaide Proteomics Centre, School of Biological Sciences, The University of Adelaide, Adelaide, South Australia, Australia.
Discipline of Obstetrics and Gynaecology, School of Medicine, Robinson Research Institute, The University of Adelaide, Adelaide, South Australia, Australia.
Transl Res. 2016 May;171:83-95.e1-2. doi: 10.1016/j.trsl.2016.02.002. Epub 2016 Feb 10.
Annexin A2, a calcium phospholipid binding protein, has been shown to play an important role in ovarian cancer metastasis. This study examined whether annexin A2 and S100A10 can be used as prognostic markers in serous ovarian cancer. ANXA2 and S100A10 gene expressions were assessed in publicly available ovarian cancer data sets and annexin A2 and S100A10 protein expressions were assessed by immunohistochemistry in a uniform cohort of stage III serous ovarian cancers (n = 109). Kaplan-Meier and Cox regression analyses were performed to assess the relationship between annexin A2 or S100A10 messenger RNA (mRNA) and protein expressions with clinical outcome. High ANXA2 mRNA levels in stage III serous ovarian cancers were associated with reduced progression-free survival (PFS; P = 0.023) and overall survival (OS; P = 0.0038), whereas high S100A10 mRNA levels predicted reduced OS (P = 0.0019). Using The Cancer Genome Atlas data sets, ANXA2 but not S100A10 expression was associated with higher clinical stage (P = 0.005), whereas both ANXA2 and S100A10 expressions were associated with the mesenchymal molecular subtype (P < 0.0001). Kaplan-Meier and Cox regression analyses showed that high stromal annexin A2 immunostaining was significantly associated with reduced PFS (P = 0.013) and OS (P = 0.044). Moreover, high cytoplasmic S100A10 staining was significantly associated with reduced OS (P = 0.027). Multivariate Cox regression analysis showed stromal annexin A2 (P = 0.009) and cytoplasmic S100A10 (P = 0.016) levels to be independent predictors of OS. Patients with high stromal annexin A2 and high cytoplasmic S100A10 expressions had a 3.4-fold increased risk of progression (P = 0.02) and 7.9-fold risk of ovarian cancer death (P = 0.04). Our findings indicate that together annexin A2 and S100A10 expressions are powerful predictors of serous ovarian cancer outcome.
膜联蛋白A2是一种钙磷脂结合蛋白，已被证明在卵巢癌转移中起重要作用。本研究检测了膜联蛋白A2和S100A10是否可作为浆液性卵巢癌的预后标志物。在公开的卵巢癌数据集中评估了ANXA2和S100A10基因表达，并通过免疫组织化学在一组统一的III期浆液性卵巢癌患者（n = 109）中评估了膜联蛋白A2和S100A10蛋白表达。进行了Kaplan-Meier和Cox回归分析，以评估膜联蛋白A2或S100A10信使核糖核酸（mRNA）及蛋白表达与临床结局之间的关系。III期浆液性卵巢癌中高ANXA2 mRNA水平与无进展生存期（PFS；P = 0.023）和总生存期（OS；P = 0.0038）降低相关，而高S100A10 mRNA水平预示着OS降低（P = 0.0019）。利用癌症基因组图谱数据集，ANXA2表达而非S100A10表达与更高的临床分期相关（P = 0.005），而ANXA2和S100A10表达均与间充质分子亚型相关（P < 0.0001）。Kaplan-Meier和Cox回归分析显示，高基质膜联蛋白A2免疫染色与PFS降低（P = 0.013）和OS降低（P = 0.044）显著相关。此外，高细胞质S100A10染色与OS降低显著相关（P = 0.027）。多变量Cox回归分析显示，基质膜联蛋白A2（P = 0.009）和细胞质S100A10（P = 0.016）水平是OS的独立预测因素。基质膜联蛋白A2高表达和细胞质S100A10高表达的患者进展风险增加3.4倍（P = 0.02），卵巢癌死亡风险增加7.9倍（P = 0.04）。我们的研究结果表明，膜联蛋白A2和S100A10表达共同是浆液性卵巢癌结局的有力预测指标。
