Down-regulation of proteasomal subunit MB1 is an independent predictor of improved survival in ovarian cancer

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• 作者：Ninke Leffers ; Marloes J.M. Gooden ; Anna A. Mokhova ; W. Martin Kast ; H. Marike Boezen ; Klaske A. ten Hoor ; Harry Hollema ; Toos Daemen ; Ate G.J. van der Zee ; Hans W. Nijman
• 关键词：Ovarian cancer ; Proteasome ; Antigen processing ; Antigen presentation ; MB1
• 刊名：Gynecologic Oncology
• 出版年：2009
• 出版时间：May 2009
• 年：2009
• 卷：113
• 期：2
• 页码：256-263
• 全文大小：4343 K

文摘

Objective

To investigate the expression and to determine the prognostic impact of components of the antigen processing and presentation pathway (APPP) in ovarian cancer.

Methods

Expression of MB1, LMP7, TAP1, TAP2, ERp57, ERAP1, β₂-microglobulin and the α-chains, HLA-B/C and HLA-A, of the MHC class I molecules was evaluated on tissue microarrays containing primary tumor samples from 232 FIGO stages I–IV ovarian cancer patients. Expression levels were correlated to clinicopathological data and disease specific (DSS) survival.

Results

Patients with expression of all components of the MHC class I complex, i.e. HLA-A⁺–β₂-m⁺ and HLA-B/C⁺–β₂-m⁺ patients, more often had expression of LMP7, a component of the immunoproteasome than patients with other phenotypes (p < 0.001). These patients were also more prone to loss of MB1, part of the constitutive multicatalytic proteasome (p < 0.05). Nuclear MB1 expression was an independent predictor of worse DSS (HR 1.94, 95 % CI 1.16–3.26, p = 0.012). The HLA-B/C⁺–β₂-m⁺ phenotype was an independent predictor of a better prognosis (HR 0.63, 95 % CI 0.40–0.99, p = 0.047). Median DSS was longer for patients with normal nuclear expression of LMP7 (57.4 vs. 31.0 months, p = 0.029).

Conclusions

The prognostic influence of the proteasomal subunit MB1 and the MHC class I complex in ovarian cancer provides a rationale for targeting these specific APPP components in ovarian cancer.