Diagnostic and prognostic impact of serum-soluble UL16-binding protein 2 in lung cancer patients

Diagnostic and prognostic impact of serum-soluble UL16-binding protein 2 in lung cancer patients
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DOI:
10.1111/j.1349-7006.2012.02330.x
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发表时间:
2012-08-01
期刊:
影响因子:
5.7
通讯作者:
Shimizu, Eiji
Shimizu, Eiji
中科院分区:
医学2区
文献类型:
--
作者:
Yamaguchi, Kosuke;Chikumi, Hiroki;Shimizu, Eiji

文献摘要

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UL 16结合蛋白2(ULBP 2)是NKG 2D(NKG 2DL)的配体之一。ULBP 2表达在转化细胞中被诱导,并通过激活NKG 2D免疫受体被免疫效应细胞识别。已报告在患有几种类型的癌症的患者的血清中存在可溶性形式的NKG 2DL。本研究探讨血清可溶性ULBP 2(sULBP 2)在肺癌患者中的诊断和预后意义。我们使用流式细胞术评估各种肺癌细胞的NKG 2DL表面表达,而使用我们最初的ELISA测量sULBP 2。此外,通过51 Cr释放试验检测了sULBP 2对外周血单个核细胞(PBMC)的免疫效应。我们发现ULBP 2是高度表达的,并且在培养的非小细胞肺癌(NSCLC)细胞的上清液中以及在NSCLC患者的血清中sULBP 2水平升高。ULBP 2水平在鳞状细胞癌(SQ)患者中特别高。sULBP 2水平=8.7 pg/mL的临床IIIB和IV期NSCLC患者的生存期显著短于sULBP 2水平=8.7 pg/mL的患者。
UL16-binding protein 2 (ULBP2) is one of the ligands for NKG2D (NKG2DL). ULBP2 expression is induced in transformed cells and is recognized by immune effector cells via the activating NKG2D immunoreceptor. Soluble forms of NKG2DL have been reported in the serum of patients with several types of cancer. The present study investigated the diagnostic and prognostic significance of serum-soluble ULBP2 (sULBP2) in lung cancer patients. We used flow cytometry to evaluate the surface expression of NKG2DL by various lung cancer cells, while sULBP2 was measured using our original ELISA. In addition, the immunological effect of sULBP2 on peripheral blood mononuclear cells (PBMC) was examined by the 51Cr release assay. We found that ULBP2 was highly expressed and that the sULBP2 level was elevated in supernatants of cultured non-small-cell lung cancer (NSCLC) cells as well as in the serum of NSCLC patients. ULBP2 levels were especially high in squamous cell carcinoma (SQ) patients. Clinical stage IIIB and IV NSCLC patients with a sULBP2 level =8.7 pg/mL showed significantly shorter survival than patients with sULBP2