Clinic of Obstetrics and Gynaecology, Medical Faculty, University of Duisburg-Essen, Germany.
Gynecol Oncol. 2011 Feb;120(2):233-8. doi: 10.1016/j.ygyno.2010.10.014. Epub 2010 Nov 13.
Intracellularly, the ubiquitin-proteasome system participates in crucial functions such as cell cycling, differentiation, proliferation, gene transcription, and apoptosis. However, in malignancies including ovarian cancer increased extracellular concentrations of circulating 20S proteasomes (c-proteasomes) have been detected in blood. We tested the hypothesis that the c-proteasome plasma concentration is a biomarker associated with the clinical course of ovarian cancer patients.
20S-proteasome venous plasma concentration was measured by ELISA in patients presenting with ovarian cancer before (n=120) and after (n=68) primary treatment, and in healthy volunteers (n=55). The median follow-up time was 19 months. To assess the relation of proteasome expression with c-proteasome concentration, tumor specimens from 27 patients were immunohistochemically stained for 20S proteasome using an antibody directed against the core subunits of the catalytic domain of the 20S proteasome.
Median c-proteasome concentration was higher (p<0.0001) in untreated ovarian cancer patients (457.5 ng/ml, range: 200-12540 ng/ml) than in healthy controls 290 ng/ml, range: 140-425 ng/ml). Following completion of primary treatment, the median c-proteasome concentration increased (p=0.003) relative to baseline (595 ng/ml, range: 200-20000 ng/ml) and concentrations positively correlated (p=0.031) with residual disease left at primary surgery. Patients with post-treatment c-proteasome concentrations exceeding the cohort's median showed a diminished survival (p=0.045). We found no correlation between c-proteasome concentration and strength of proteasomal staining in tumor specimens.
Circulating proteasome concentrations correlate with residual tumor mass and might be a prognostic variable in ovarian cancer following primary therapy.
细胞内，泛素-蛋白酶体系统参与细胞周期、分化、增殖、基因转录和凋亡等重要功能。然而，在包括卵巢癌在内的恶性肿瘤中，已在血液中检测到循环 20S 蛋白酶体（c-proteasomes）的细胞外浓度增加。我们检验了这样一个假设，即 c-proteasome 血浆浓度是与卵巢癌患者临床病程相关的生物标志物。
通过 ELISA 测量呈现卵巢癌的患者在初次治疗前（n=120）和后（n=68）的静脉血浆 20S-蛋白酶体浓度，以及健康志愿者（n=55）的血浆浓度。中位随访时间为 19 个月。为了评估蛋白酶体表达与 c-proteasome 浓度的关系，使用针对 20S 蛋白酶体催化结构域核心亚基的抗体对 27 例患者的肿瘤标本进行了免疫组织化学染色。
未经治疗的卵巢癌患者的中位 c-proteasome 浓度更高（p<0.0001）（457.5ng/ml，范围：200-12540ng/ml），高于健康对照者的 290ng/ml，范围：140-425ng/ml）。完成初次治疗后，与基线相比，c-proteasome 浓度升高（p=0.003）（595ng/ml，范围：200-20000ng/ml），且浓度与初次手术时残留的疾病呈正相关（p=0.031）。治疗后 c-proteasome 浓度超过队列中位数的患者生存时间缩短（p=0.045）。我们未发现 c-proteasome 浓度与肿瘤标本中蛋白酶体染色强度之间存在相关性。
循环蛋白酶体浓度与残留肿瘤量相关，可能是卵巢癌初次治疗后预后的一个变量。
