Harel-Dassa Keren, Yedgar Saul, Tropé Claes G, Davidson Ben, Reich Reuven
Institute of Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel; Department of Biochemistry, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
Department of Biochemistry, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
Hum Pathol. 2017 Apr;62:115-121. doi: 10.1016/j.humpath.2016.12.023. Epub 2017 Jan 11.
The objective of this study was to analyze the expression and clinical role of phospholipase D (PLD) in high-grade serous carcinoma (HGSC). PLD1 and PLD2 isoform expression was studied in 125 HGSC specimens (73 effusions, 28 ovarian tumors, 24 solid metastases) using quantitative real-time reverse-transcription polymerase chain reaction. Expression levels were analyzed for association with clinicopathological parameters, including chemoresponse, and survival. PLD1 and PLD2 isoforms were found in most specimens at all anatomic sites, and their levels were strongly positively related (P<.001 for effusions and solid lesions). PLD2 messenger RNA (mRNA) expression was significantly higher in effusions compared with both carcinomas in the ovary and solid metastases (P<.001). Higher levels of both isoforms were associated with higher CA 125 levels at diagnosis (P<.001), and higher PLD2 mRNA levels in effusions were associated with unfavorable response to chemotherapy (P=.021). Expression levels of the studied isoforms were unrelated to the levels of previously studied mRNAs that form part of the phospholipase A pathway or to survival. The present study provides the first evidence of PLD expression in HGSC and suggests a role in mediating progression to effusions and chemoresistance in this cancer.
本研究的目的是分析磷脂酶D（PLD）在高级别浆液性癌（HGSC）中的表达及临床作用。使用定量实时逆转录聚合酶链反应，对125例HGSC标本（73例积液、28例卵巢肿瘤、24例实体转移灶）中的PLD1和PLD2亚型表达进行了研究。分析表达水平与包括化疗反应和生存在内的临床病理参数之间的相关性。在所有解剖部位的大多数标本中均发现了PLD1和PLD2亚型，且它们的水平呈强正相关（积液和实体病变的P<0.001）。与卵巢癌和实体转移灶相比，积液中的PLD2信使核糖核酸（mRNA）表达显著更高（P<0.001）。两种亚型的较高水平与诊断时较高的CA 125水平相关（P<0.001），积液中较高的PLD2 mRNA水平与化疗不良反应相关（P=0.021）。所研究亚型的表达水平与磷脂酶A途径中先前研究的mRNA水平或生存无关。本研究首次提供了HGSC中PLD表达的证据，并提示其在介导该癌症进展为积液和化疗耐药中发挥作用。
