Sinreih Maša, Štupar Saša, Čemažar Luka, Verdenik Ivan, Frković Grazio Snježana, Smrkolj Špela, Rižner Tea Lanišnik
Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
J Steroid Biochem Mol Biol. 2017 Jul;171:43-53. doi: 10.1016/j.jsbmb.2017.02.015. Epub 2017 Feb 21.
Endometrial cancer is the most frequent gynecological malignancy in the developed world. The majority of cases are estrogen dependent, and are associated with diminished protective effects of progesterone. Endometrial cancer is also related to enhanced inflammation and decreased differentiation. In our previous studies, we examined the expression of genes involved in estrogen and progesterone actions in inflammation and tumor differentiation, in tissue samples from endometrial cancer and adjacent control endometrium. The aims of the current study were to examine correlations between gene expression and several demographic characteristics, and to evaluate changes in gene expression with regard to histopathological and clinical characteristics of 51 patients. We studied correlations and differences in expression of 38 genes involved in five pathophysiological processes: (i) estrogen-stimulated proliferation; (ii) estrogen-dependent carcinogenesis; (iii) diminished biosynthesis of progesterone: (iv) enhanced formation of progesterone metabolites; and (v) increased inflammation and decreased differentiation. Spearman correlation coefficient analysis shows that expression of PAQR7 correlates with age, expression of SRD5A1, AKR1B1 and AKR1B10 correlate with body mass, while expression of SRD5A1 and AKR1B10 correlate with body mass index. When patients with endometrial cancer were stratified based on menopausal status, histological grade, myometrial invasion, lymphovascular invasion, and FIGO stage, Mann-Whitney U tests revealed significantly decreased expression of STAR (4.4-fold; adjusted p=0.009) and AKR1B10 (9-fold; adjusted p=0.003) in high grade versus low grade tumors. Lower levels of STAR might lead to decreased de-novo steroid hormone synthesis and tumor differentiation, and lower levels of AKR1B10 to diminished elimination of toxic electrophilic carbonyl compounds in high-grade endometrial cancer. These data thus reveal the potential of STAR and AKR1B10 as prognostic biomarkers, which calls for further validation at the protein level.
子宫内膜癌是发达国家最常见的妇科恶性肿瘤。大多数病例依赖雌激素，并与孕酮的保护作用减弱有关。子宫内膜癌还与炎症增强和分化降低有关。在我们之前的研究中，我们检测了子宫内膜癌组织样本及相邻对照子宫内膜中参与雌激素和孕酮作用、炎症及肿瘤分化的基因表达。本研究的目的是检测基因表达与若干人口统计学特征之间的相关性，并评估51例患者基因表达在组织病理学和临床特征方面的变化。我们研究了参与五个病理生理过程的38个基因的表达相关性及差异：（i）雌激素刺激的增殖；（ii）雌激素依赖性致癌作用；（iii）孕酮生物合成减少；（iv）孕酮代谢产物形成增加；（v）炎症增加和分化降低。Spearman相关系数分析表明，PAQR7的表达与年龄相关，SRD5A1、AKR1B1和AKR1B10的表达与体重相关，而SRD5A1和AKR1B10的表达与体重指数相关。根据绝经状态、组织学分级、肌层浸润、淋巴血管浸润和国际妇产科联盟（FIGO）分期对子宫内膜癌患者进行分层时，Mann-Whitney U检验显示，高级别肿瘤与低级别肿瘤相比，STAR（4.4倍；校正p = 0.009）和AKR1B10（9倍；校正p = 0.003）的表达显著降低。STAR水平较低可能导致类固醇激素从头合成减少和肿瘤分化降低，而AKR1B10水平较低可能导致高级别子宫内膜癌中有毒亲电羰基化合物的清除减少。因此，这些数据揭示了STAR和AKR1B10作为预后生物标志物的潜力，这需要在蛋白质水平上进一步验证。
