The clinical role of phospholipase A2 isoforms in advanced-stage ovarian carcinoma
The clinical role of phospholipase A2 isoforms in advanced-stage ovarian carcinoma
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DOI：
10.1016/j.ygyno.2006.06.042
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发表时间：
2006-12-01
影响因子：
4.7
通讯作者：
Reich, Reuven
中科院分区：
文献类型：
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作者：
Gorovetz, Michal;Baekelandt, Mark;Reich, Reuven
目标。分析晚期（FIGOⅲ~ⅳ期）卵巢癌中磷脂酶A(2) （PLA(2)）亚型的表达及其与基质金属蛋白酶（MMP）表达及临床参数的关系。采用逆转录聚合酶链式反应（RT-PCR）对77例卵巢癌患者新鲜冷冻液中10种分泌性PLA2 （sPLA(2)）亚型（IB、IIA/D/E/F、III、V、X、XII和XIII）、PLA(2)受体（sPLA(2)R）、细胞质PLA2 （cPLA(2)）、PLA(2)活化蛋白（PLAP）和MMP-2的信使RNA （mRNA）表达进行了研究。应用免疫组织化学方法研究52例积液中磷酸化cPLA(2) （p-cPLA(2)）蛋白的表达。利用酶谱法分别对22例和20例积液的MMP-2和MMP-9活性进行评估。分析表达与临床病理参数、化疗状态及生存的相关性。95%的标本均表达PLA(2)亚型、sPLA(2)R、PLAP和MMP-2 mRNA。p-cPLA(2)蛋白在46/52（88%）的积液中表达。所有标本均检测到MMP-2活性，而19/20的积液中检测到MMP-9活性。发现MMP-2与p- cpla (2) （p=0.003）和sPLA(2)-IIA （p=0.021）共表达。化疗后积液中sPLA(2)-IIA表达较低（p < 0.001）， sPLA(2)-V （p=0.038）和sPLA(2)-XIII表达较高（p=0.001）。在单变量生存分析中，较高水平的sPLA2-V与较好的总生存（OS, p=0.021）和无进展生存（PFS, p= 0.025）相关。对于化疗后积液患者，FIGO IV期和较高的PLAP mRNA表达与较差的OS相关（PLAP和分期均为p = 0.005），而较高的PLAP （p = 0.025）和sPLA(2)-XII （p = 0.027）水平和FIGO IV期（p < 0.001）与较短的PFS相关。在Cox多因素分析中，PLAP表达（p= 0.022）和FIGO分期（p=0.036）独立预测OS较差，而sPLA(2)-XII水平升高（p=0.04）和FIGO分期（p= 0.003）是pfs较短的独立预测因子。本研究首次报道了PLA(2)亚型、sPLA(2)R和PLAP在卵巢癌中的表达。化疗前后标本中PLA(2)同工酶表达不同。PLAP和sPLA(2)-XII可能是化疗后积液患者预后不良的独立预测因子。(c) 2006爱思唯尔公司版权所有。
Objective. To analyze the expression of phospholipase A(2) (PLA(2)) isoforms and its relationship with matrix metalloprotemase (MMP) expression and clinical parameters in advanced-stage (FIGO III-IV) ovarian carcinoma.Methods. Seventy-seven fresh frozen effusions from ovarian carcinoma patients were studied for messenger RNA (mRNA) expression of 10 secretory PLA2 (sPLA(2)) isoforms (IB, IIA/D/E/F, III, V, X, XII and XIII), the PLA(2) receptor (sPLA(2)R), cytoplasmic PLA2 (cPLA(2)), PLA(2)-activating protein (PLAP) and MMP-2 using reverse transcription polymerase chain reaction (RT-PCR). Phosphorylated cPLA(2) (p-cPLA(2)) protein expression was studied in 52 effusions using immunohistochemistry. MMP-2 and MMP-9 activity was evaluated in 22 and 20 effusions, respectively, using zymography. Expression was analyzed for correlation with clinicopathologic parameters, chemotherapy status and survival.Results. PLA(2) isoforms, sPLA(2)R, PLAP and MMP-2 mRNA was expressed in > 95% of specimens. p-cPLA(2) protein was expressed in 46/52 (88%) effusions. MMP-2 activity was found in all specimens, while that of MMP-9 was detected in 19/20 effusions. MMP-2 was found to be coexpressed with p-cPLA(2) (p=0.003) and sPLA(2)-IIA (p=0.021). Lower expression of sPLA(2)-IIA (p < 0.001) and higher expression of sPLA(2)-V (p=0.038) and sPLA(2)-XIII (p=0.001) was found in post-chemotherapy effusions. In univariate survival analysis, higher levels of sPLA2-V correlated with better overall (OS, p=0.021) and progression-free (PFS, p= 0.025) survival. For patients with post-chemotherapy effusions, FIGO stage IV and higher PLAP mRNA expression correlated with worse OS (p = 0.005 for both PLAP and stage), while higher PLAP (p = 0.025) and sPLA(2)-XII (p = 0.027) levels and FIGO stage IV (p < 0.001) correlated with shorter PFS. In Cox multivariate analysis, PLAP expression (p = 0.022) and FIGO stage (p=0.036) independently predicted poor OS, while higher sPLA(2)-XII levels (p=0.04) and FIGO stage (P=0.003) were independent predictors of shorter PFS.Conclusions. The present study documents for the first time expression of PLA(2) isoforms, sPLA(2)R and PLAP in ovarian carcinoma. PLA(2) isoenzyme expression differs in pre- and post-chemotherapy specimens. PLAP and sPLA(2)-XII may be independent predictors of poor outcome for patients with post-chemotherapy effusions. (c) 2006 Elsevier Inc. All rights reserved.