cPLAa 通过促进上皮-间充质转化与骨肉瘤的转移和不良预后相关。
cPLAa correlates with metastasis and poor prognosis of osteosarcoma by facilitating epithelial-mesenchymal transition.
机构信息
Department of Oncology, Yidu Central Hospital of Weifang City, Weifang, China.
Department of Orthopedic Surgery, Yidu Central Hospital of Weifang City, Weifang, China.
出版信息
Pathol Res Pract. 2019 Jun;215(6):152398. doi: 10.1016/j.prp.2019.03.026. Epub 2019 Mar 27.
BACKGROUND
Osteosarcoma (OS) patients with metastasis have very dismal prognoses, and lack effective target therapies. Overexpression of cytosolic phospholipase A2 (cPLA) has been shown to promote progression in several types of cancers, but its functions in OS have not been investigated.
MATERIALS AND METHODS
In our study, the expression of cPLAa was detected with immunohistochemistry in 102 cases of OS. The clinical significance of cPLAa was evaluated by analyzing its correlation with clinicopathological factors. The prognostic significance of cPLAa was estimated by univariate and multivariate analysis. The oncogenic functions of cPLAa on cell proliferation and invasion were investigated by MTT assay and tranwell assay respectively. Western blotting was applied to detect the markers of epithelial-mesenchymal transition (EMT) after silencing cPLAa expression or inhibiting its activity by a specific antagonist.
RESULTS
In our study, high expression of cPLAa was significantly associated with metastasis and advanced Enneking stage. High cPLAa expression was significantly associated with poor prognosis and it was an independent prognostic biomarker of OS. By silencing cPLAa or inhibiting its activity by a specific antagonist, we demonstrated that cPLAa promoted cell invasion of OS cells via inducing the EMT process.
CONCLUSIONS
High cPLAa expression was an independent prognostic biomarker of OS, and cPLAa could promote OS cell invasion via inducing the EMT process, indicating that cPLAa was an independent prognostic biomarker and may be an effective drug target for OS.
背景
患有转移的骨肉瘤(OS)患者预后极差,缺乏有效的靶向治疗方法。细胞溶质磷脂酶 A2(cPLA2)的过表达已被证明可促进几种类型的癌症的进展,但它在 OS 中的功能尚未被研究。
材料和方法
在我们的研究中,用免疫组织化学检测了 102 例 OS 中 cPLAa 的表达。通过分析其与临床病理因素的相关性,评估 cPLAa 的临床意义。通过单因素和多因素分析估计 cPLAa 的预后意义。通过 MTT 测定和 tranwell 测定分别研究了 cPLAa 对细胞增殖和侵袭的致癌作用。通过沉默 cPLAa 表达或用特异性拮抗剂抑制其活性,用 Western blot 检测上皮-间充质转化(EMT)的标记物。
结果
在我们的研究中,cPLAa 的高表达与转移和晚期 Enneking 分期显著相关。高 cPLAa 表达与预后不良显著相关,是 OS 的独立预后生物标志物。通过沉默 cPLAa 或用特异性拮抗剂抑制其活性,我们证明 cPLAa 通过诱导 EMT 过程促进 OS 细胞的侵袭。
结论
高 cPLAa 表达是 OS 的独立预后生物标志物,cPLAa 可通过诱导 EMT 过程促进 OS 细胞的侵袭,表明 cPLAa 是独立的预后生物标志物,可能是 OS 的有效药物靶点。