Wasniewski Tomasz, Woclawek-Potocka Izabela, Boruszewska Dorota, Kowalczyk-Zieba Ilona, Sinderewicz Emilia, Grycmacher Katarzyna
Department of Gynecology and Obstetrics, Faculty of Medical Sciences, University of Warmia and Masuria, 10-561 Olsztyn, Poland.
Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-747 Olsztyn, Poland.
Oncol Rep. 2015 Nov;34(5):2760-7. doi: 10.3892/or.2015.4216. Epub 2015 Aug 20.
In order to study lysophosphatidic acid (LPA) signaling associated with type 1 endometrial carcinoma (EC), we evaluated the LPA receptors (LPARs), autotaxin (ATX) and phospholipase A2 (PLA2) expression in EC and normal endometrium with correlation to clinicopathological features. We investigated LPAR1, LPAR2, LPAR3, LPAR4, ATX and PLA2 expression at mRNA and protein levels using quantitative real-time PCR and western blot analyses in 37 ECs and 10 normal endometria. All the examined LPARs (except for LPAR3 protein), ATX and PLA2 were overexpressed in cancerous compared to healthy endometrium. The studied ECs showed the highest LPAR2 and LPAR1 expression. Statistically positive correlations were found between depth of myoinvasion and levels of LPAR1, LPAR2 and PLA2 transcripts and proteins. We also found positive correlations between LPAR1, LPAR2, LPAR4 and PLA2 expression with the International Federation of Gynecology and Obstetrics (FIGO) stage. The expression of LPAR1, LPAR2 and PLA2 was positively associated with the age of patients. Positive correlations were found between the expression of LPAR1 mRNA, LPAR2 mRNA and protein and LPAR3 mRNA and body mass index (BMI) of the examined patients. We found no association between the expression levels of the studied factors and diabetes or hypertension among the examined patients. Owing to the highest LPAR2 and LPAR1 expression in EC and positive correlations of these two receptors with the depth of myoinvasion and the FIGO stage, we believe that LPAR2 and LPAR1 show promise as predictors of the EC progression as well as the main receptors responsible for LPA action in the EC tissue.
为了研究与1型子宫内膜癌（EC）相关的溶血磷脂酸（LPA）信号传导，我们评估了EC和正常子宫内膜中LPA受体（LPARs）、自分泌运动因子（ATX）和磷脂酶A2（PLA2）的表达，并将其与临床病理特征相关联。我们使用定量实时PCR和蛋白质印迹分析，在37例EC和10例正常子宫内膜中，研究了LPAR1、LPAR2、LPAR3、LPAR4、ATX和PLA2在mRNA和蛋白质水平的表达。与健康子宫内膜相比，所有检测的LPARs（LPAR3蛋白除外）、ATX和PLA2在癌组织中均过表达。所研究的EC中LPAR2和LPAR1表达最高。肌层浸润深度与LPAR1、LPAR2和PLA2转录本及蛋白质水平之间存在统计学上的正相关。我们还发现LPAR1、LPAR2、LPAR4和PLA2表达与国际妇产科联合会（FIGO）分期之间存在正相关。LPAR1、LPAR2和PLA2的表达与患者年龄呈正相关。在所检测患者中，LPAR1 mRNA、LPAR2 mRNA和蛋白质以及LPAR3 mRNA的表达与体重指数（BMI）之间存在正相关。我们未发现所研究因素的表达水平与所检测患者中的糖尿病或高血压之间存在关联。由于LPAR2和LPAR1在EC中表达最高，且这两种受体与肌层浸润深度和FIGO分期呈正相关，我们认为LPAR2和LPAR1有望作为EC进展的预测指标以及EC组织中LPA作用的主要受体。
