Abstract
Major histocompatibility complex class I chain-related A (MICA) is a stress-inducible glycoprotein that can be shed as a soluble protein. This study was conducted to determine the expression of MICA in renal cell carcinoma (RCC) and examine the clinical relevance of soluble MICA (sMICA) in this disease. Immunohistochemistry and real-time PCR analyses were performed to assess the expression of MICA in 48 pairs of RCC and adjacent normal renal tissues. Serum levels of sMICA were measured in 48 RCC patients, 12 patients with benign renal tumors, and 20 healthy individuals. The correlations between sMICA levels and clinicopathological parameters were analyzed and the diagnostic performance of sMICA in RCC was evaluated. RCCs exhibited elevated expression of MICA compared to adjacent normal tissues. Serum concentrations of sMICA were significantly greater in RCC patients (348.5 ± 32.5 pg/ml) than those with benign disease (289.3 ± 30.4 pg/ml) and healthy controls (168.4 ± 43.2 pg/ml) and significantly correlated with advanced tumor stage, lymph node metastasis, distant metastasis, vascular invasion, and higher histological grade. Using a cut-off point of 250 pg/ml, sMICA demonstrated a specificity and sensitivity of 63.2% and 75.6%, respectively, in distinguishing between RCC and benign renal tumors. MICA expression is upregulated in RCC and increased serum sMICA levels predict aggressive tumor behavior. However, the applicability of sMICA alone is limited in distinguishing RCC from benign renal tumors.
Highlights
Renal cell carcinoma (RCC) is the most common type (>80%) of renal malignancies and leads to more than 100,000 deaths per year worldwide (Parkin et al, 2002)
Major histocompatibility complex class I chain-related A (MICA) is able to bind to the immunoreceptor NKG2D and mediate the cyotoxicity of NK and T cells against tumor cells (Oppenheim et al, 2005), playing a key role in tumor immunosurveillance
MICA is regarded as a stress-inducible molecule
Summary
Renal cell carcinoma (RCC) is the most common type (>80%) of renal malignancies and leads to more than 100,000 deaths per year worldwide (Parkin et al, 2002). MHC class I polypeptide-related chain A (MICA) is a stress-inducible glycoprotein and frequently expressed in epithelial tumors (Kohga et al, 2010; Zhao et al, 2012). It acts a natural ligand for NKG2D to activate antitumor effects of natural killer (NK) cells and T cells. In oral squamous cell carcinoma, serum levels of sMICA are useful in the diagnosis of stage IV disease and as an indicator of regional lymph node metastasis (Tamaki et al, 2008). In this study we sought to determine tissue expression and serum concentrations of MICA in RCC patients and examine the clinical relevance of sMICA in this disease
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