Clinical significance of the NKG2D ligands, MICA/B and ULBP2 in ovarian cancer: high expression of ULBP2 is an indicator of poor prognosis
Clinical significance of the NKG2D ligands, MICA/B and ULBP2 in ovarian cancer: high expression of ULBP2 is an indicator of poor prognosis
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DOI：
10.1007/s00262-008-0585-3
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发表时间：
2009-05-01
影响因子：
5.8
通讯作者：
Konishi, Ikuo
中科院分区：
文献类型：
--
作者：
Li, Kui;Mandai, Masaki;Konishi, Ikuo
为探讨NKG 2D配体云母/B和ULBP 2在卵巢癌中表达的临床意义，选取1993 ~ 2003年在京都大学附属医院妇产科就诊的82例卵巢癌患者和6例非卵巢癌患者作为研究对象。通过免疫组化染色评估卵巢癌组织和正常卵巢组织中云母/B、ULBP 2和CD 57的表达，并分析这些结果与相关临床患者数据的关系。检测了33株卵巢癌细胞系和2株正常卵巢上皮细胞系中MIC、ULBP 2和HLA-I类分子的表达，以及培养上清液中可溶性MIC和ULBP 2的水平，分别在97.6%和82.9%的卵巢癌细胞中检测到云母/B和ULBP 2的表达，而在正常卵巢上皮细胞中均不表达。卵巢癌中云母/B的表达与ULBP 2的表达高度相关。ULBP 2在卵巢癌细胞中的强表达与上皮内T细胞浸润较少和患者的不良预后相关，表明ULBP 2表达是卵巢癌的预后指标。NKG 2D配体的表达与可溶性配体的水平无关，ULBP 2的高表达是卵巢癌预后不良的指标，可能与肿瘤微环境中的T细胞功能障碍有关。
To investigate the clinical significance of the expression of the NKG2D ligands MICA/B and ULBP2 in ovarian cancer.Eighty-two ovarian cancer patients and six patients without ovarian cancer from Department of Obstetrics and Gynecology of Kyoto University Hospital were enrolled in this study between 1993 and 2003. Expression of MICA/B, ULBP2, and CD57 in ovarian cancer tissue and normal ovary tissue was evaluated by immunohistochemical staining, and the relationship of these results to relevant clinical patient data was analyzed. Expression of MICs, ULBP2, and HLA-class I molecules in 33 ovarian cancer cell lines and two normal ovarian epithelial cell lines, as well as levels of soluble MICs and ULBP2 in the culture supernatants, were measured.Expression of MICA/B and ULBP2 was detected in 97.6 and 82.9% of ovarian cancer cells, respectively, whereas neither was expressed on normal ovarian epithelium. The expression of MICA/B in ovarian cancer was highly correlated with that of ULBP2. Strong expression of ULBP2 in ovarian cancer cells was correlated with less intraepithelial infiltration of T cells and bad prognoses for patients, suggesting that ULBP2 expression is a prognostic indicator in ovarian cancer. The expression of NKG2D ligands did not correlate with the levels of the soluble forms of the ligands.High expression of ULBP2 is an indicator of poor prognosis in ovarian cancer and may relate to T cell dysfunction in the tumor microenvironment.