Czogalla Bastian, Partenheimer Alexandra, Badmann Susann, Schmoeckel Elisa, Mayr Doris, Kolben Thomas, Beyer Susanne, Hester Anna, Burges Alexander, Mahner Sven, Jeschke Udo, Trillsch Fabian
Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Munich, Germany.
Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Munich, Germany.
Transl Oncol. 2021 Jan;14(1):100910. doi: 10.1016/j.tranon.2020.100910. Epub 2020 Oct 14.
Enolase-1, primarily known for its role in glucose metabolism, is overexpressed in various cancer entities. In contrast its alternative spliced nuclear isoform MBP-1 acts as a tumor suppressor. The aim of this study is to analyze the prognostic impact of Enolase-1/ MBP-1 and its functional significance in epithelial ovarian cancer (EOC).
By immunohistochemistry, Enolase-1 staining was examined in 156 EOC samples. Evaluation of Enolase-1 staining was conducted in the nucleus and the cytoplasm using the semi-quantitative immunoreactive score. Expression levels were correlated with clinical and pathological parameters as well as with overall survival to assess for prognostic impact.
Cytoplasmic and nuclear Enolase-1 expression did not show a significant difference between the histological subtypes (p = 0.1). High nuclear Enolase-1/ MBP-1 staining negativly correlated with the tumor grading (p<0.001; Cc= -0.318). Cytoplasmic Enolase-1 did not correlate with clinicopathological data. Higher nuclear Enolase-1/ MBP-1 staining was detected in low-grade serous cancer cases compared to high-grade ones (median IRS 3 (range 0-8) vs. median IRS 2 (range 0-4), p<0.001). Nuclear Enolase-1/ MBP-1 expression correlated with the Wnt signaling markers membranous beta-catenin (p = 0.007; Cc=0.235), serine residue 9-phosphorylated glycogen synthase kinase 3 beta (p<0.001; Cc=0.341) and snail/slug (p = 0.004; Cc= -0.257). High nuclear Enolase-1/ MBP-1 expression was associated with improved overall survival (88.6 vs. 33.1 months, median; p = 0.013).
Additional knowledge of Enolase-1/ MBP-1 as a biomarker and its interactions within the Wnt signaling pathway and epithelial-mesenchymal transition potentially improve the prognosis of therapeutic approaches in EOC.
烯醇化酶-1主要因其在葡萄糖代谢中的作用而闻名，在多种癌症实体中均有过表达。相比之下，其可变剪接的核异构体MBP-1发挥肿瘤抑制作用。本研究旨在分析烯醇化酶-1/MBP-1的预后影响及其在上皮性卵巢癌（EOC）中的功能意义。
通过免疫组织化学法检测156例EOC样本中的烯醇化酶-1染色情况。使用半定量免疫反应评分法对细胞核和细胞质中的烯醇化酶-1染色进行评估。将表达水平与临床和病理参数以及总生存期相关联，以评估其预后影响。
组织学亚型之间细胞质和细胞核中的烯醇化酶-1表达无显著差异（p = 0.1）。细胞核中高烯醇化酶-1/MBP-1染色与肿瘤分级呈负相关（p<0.001；Cc = -0.318）。细胞质中的烯醇化酶-1与临床病理数据无关。与高级别浆液性癌病例相比，低级别浆液性癌病例中检测到更高的细胞核烯醇化酶-1/MBP-1染色（中位免疫反应评分3（范围0-8）对中位免疫反应评分2（范围0-4），p<0.001）。细胞核烯醇化酶-1/MBP-1表达与Wnt信号标志物膜性β-连环蛋白（p = 0.007；Cc = 0.235）、丝氨酸残基9磷酸化糖原合酶激酶3β（p<0.001；Cc = 0.341）和蜗牛/蛞蝓（p = 0.004；Cc = -0.257）相关。细胞核中高烯醇化酶-1/MBP-1表达与总生存期改善相关（中位生存期88.6对33.1个月；p = 0.013）。
烯醇化酶-1/MBP-1作为一种生物标志物的更多知识及其在Wnt信号通路和上皮-间质转化中的相互作用可能改善EOC治疗方法的预后。
