Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Paschen, A; Sucker, A; Hill, B; Moll, I; Zapatka, M; Nguyen, XD; Sim, GC; Gutmann, I; Hassel, J; Becker, JC; Steinle, A; Schadendorf, D; Ugurel, S.
Differential clinical significance of individual NKG2D ligands in melanoma: soluble ULBP2 as an indicator of poor prognosis superior to S100B.
Clin Cancer Res. 2009; 15(16):5208-5215
Doi: 10.1158/1078-0432.CCR-09-0886
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- Co-Autor*innen der Med Uni Graz
- Becker Jürgen Christian
- Ugurel-Becker Selma
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- Abstract:
- PURPOSE: Cytotoxic lymphocytes interact with human tumor cells via the activating immunoreceptor NKG2D, recognizing a variety of stress-associated MIC and ULBP surface molecules. However, tumors can escape from this immunosurveillance by shedding NKG2D ligands (NKG2DL), rendering the soluble products detectable in patients' sera. EXPERIMENTAL DESIGN: To elucidate the clinical significance of NKG2DL diversity, we studied their expression on melanoma tissues and their presence as soluble molecules in sera from >200 melanoma patients and compared the latter with the well-established serum marker S100B. RESULTS: Immunohistochemistry revealed a heterogeneous expression of MIC and ULBP2 molecules between and within melanoma metastases. Compared with MIC, ULBP2 was less frequently expressed. Accordingly, elevated levels of soluble ULBP2 (sULBP2) were detected in sera of melanoma patients less frequently than elevated levels of soluble MICA (sMICA), although both soluble NKG2DL (sNKG2DL) were significantly increased compared with sera of healthy controls (P < 0.0001). Strikingly, elevated concentrations of sULBP2, but not of sMICA, were strongly associated with disease progression (P < 0.0001) and tumor load (P = 0.0003). Elevated serum levels of either sNKG2DL correlated with reduced overall survival, albeit considerably stronger for sULBP2 (P < 0.0001) than for sMICA (P = 0.011). In early-stage (I-III) melanoma patients, only sULBP2 (P < 0.0001) but neither sMICA nor S100B revealed prognostic significance. Multivariate analysis identified sULBP2 (P = 0.0015) and S100B (P = 0.013) but not sMICA as independent predictors of prognosis. CONCLUSION: Our data reveal marked differences in the clinical significance of individual sNKG2DL. Only sULBP2 is an independent predictor of prognosis, the significance of which is superior to the well-established and widely used melanoma serum marker S100B.
- Find related publications in this database (using NLM MeSH Indexing)
- Case-Control Studies -
- Female -
- Histocompatibility Antigens Class I - metabolism
- Humans -
- Intercellular Signaling Peptides and Proteins - analysis Intercellular Signaling Peptides and Proteins - blood Intercellular Signaling Peptides and Proteins - metabolism Intercellular Signaling Peptides and Proteins - physiology
- Male -
- Melanoma - blood Melanoma - diagnosis Melanoma - metabolism Melanoma - pathology
- Middle Aged -
- NK Cell Lectin-Like Receptor Subfamily K - blood NK Cell Lectin-Like Receptor Subfamily K - metabolism NK Cell Lectin-Like Receptor Subfamily K - physiology
- Neoplasm Metastasis -
- Neoplasm Staging -
- Nerve Growth Factors - blood Nerve Growth Factors - metabolism Nerve Growth Factors - physiology
- Prognosis -
- S100 Proteins - blood S100 Proteins - metabolism S100 Proteins - physiology
- Skin Neoplasms - blood Skin Neoplasms - diagnosis Skin Neoplasms - metabolism Skin Neoplasms - pathology
- Solubility -
- Tumor Markers, Biological - blood Tumor Markers, Biological - metabolism