Kemiläinen Heidi, Huhtinen Kaisa, Auranen Annika, Carpén Olli, Strauss Leena, Poutanen Matti
Institute of Biomedicine, University of Turku, Turku, Finland.
Oncology. 2018;94(4):233-242. doi: 10.1159/000485624. Epub 2018 Jan 12.
The aim of this study was to characterize the expression of hydroxysteroid (17β) dehydrogenase type 12 (HSD17B12), an enzyme involved in the synthesis of arachidonic acid (AA), in ovarian cancer, and to study its coexpression with its upstream and downstream enzymes in the AA pathway, namely elongation of very long chain fatty acids protein 5 (ELOVL5) and cyclooxygenase-2 (COX-2), respectively.
Samples from benign and malignant ovarian neoplastic lesions were immunohistochemically stained with HSD17B12, ELOVL5, and COX-2. The staining intensities were quantified with the QuantCenter program, and the results were confirmed with visual inspection. Statistical significances were calculated with the Student t test, the Mann-Whitney test, linear regression, or ANOVA.
The expression of the HSD17B12, ELOVL5, and COX-2 enzymes increased according to the grade of the endometrioid ovarian adenocarcinomas. In contrast, in serous adenocarcinomas, staining with ELOVL5 was constantly weak, whereas the expression of HSD17B12 and COX-2 increased with the grade or FIGO stage of the cancer, respectively.
The expression of HSD17B12 increased along with the severity of ovarian cancer, and the expression mimicked COX-2 expression and intensity. This further suggests the involvement of HSD17B12 in AA production, and its coexpression with COX-2 indicates a role for the enzyme in the increased prostaglandin production during ovarian cancer progression.
本研究旨在表征17β-羟类固醇脱氢酶12(HSD17B12)的表达情况,该酶参与花生四烯酸(AA)的合成,研究其在卵巢癌中的表达,并研究其与AA途径中上游和下游酶,即超长链脂肪酸延伸蛋白5(ELOVL5)和环氧化酶-2(COX-2)的共表达情况。
用HSD17B12、ELOVL5和COX-2对良性和恶性卵巢肿瘤病变样本进行免疫组织化学染色。用QuantCenter程序对染色强度进行定量,并通过目视检查进行确认。采用学生t检验、曼-惠特尼检验、线性回归或方差分析计算统计学意义。
HSD17B12、ELOVL5和COX-2酶的表达随子宫内膜样卵巢腺癌的分级增加而增加。相反,在浆液性腺癌中,ELOVL5染色始终较弱,而HSD17B12和COX-2的表达分别随癌症分级或国际妇产科联盟(FIGO)分期增加。
HSD17B12的表达随卵巢癌严重程度增加而增加,且其表达与COX-2的表达及强度相似。这进一步表明HSD17B12参与AA生成,其与COX-2的共表达表明该酶在卵巢癌进展过程中前列腺素生成增加中发挥作用。