Abstract 4644: Significance of serum tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) levels of renal cell carcinoma patients as prognostic and monitoring biomarker
Authors: Daisuke Toiyama, Natsuki Takaha, Jun Fujiwara, Yasunori Kimura, Terukazu Nakamura, Fumiya Hongo, Kazuya Mikami, Akihiro Kawauchi, Tsuneharu Miki
Journal: Cancer Research (2010)

Abstract TRAIL and its receptors have been reported to play a significant role as cytotoxic and apoptotic mechanisms in cytotoxic T-lymphocytes and natural killer cells. TRAIL has been reported to induce apoptosis preferentially in various types of cancer cells, including renal cell carcinoma (RCC) cells. These findings suggest that TRAIL and its receptors might be useful biomarkers for RCC. In this study, we examined serum TRAIL levels of RCC patients and normal individuals and evaluated its utility as biomarker. Peripheral blood samples were obtained from 85 patients (60 men and 25 women, median age; 63 years [36-85]) with RCC before surgery. All the patients underwent radical or partial nephrectomy. The histological grade and TNM status distribution was as follows: Grade 1, n =1; Grade 2, n = 63 and Grade 3, n = 21; T1, n =56; T2, n = 8; T3, n =18 and T4, n = 3; N1-2, n = 7; and M1, n = 13. Blood samples were also collected from 52 healthy controls. The serum TRAIL levels were measured by a sandwich enzyme-linked immunosorbent assay (ELISA). The serum TRAIL levels in patients with RCC was lower than those of normal control individuals (79±8pg/ml vs 118±16 pg/ml, P =0.038). The serum TRAIL levels in RCC patients with lymph node metastasis (N1-2), distant metastasis (M1), microscopic venous invasion, and stage III-IV were significantly lower compared to those in RCC patients without lymph node metastasis (N0), without distant metastasis (M0), without microscopic venous invasion, and with stage I-II, respectively (P =0.051, P =0.045, P = 0.02, and P = 0.048). The serum TRAIL levels before and after surgery from the same patients (n = 17) was 61±15 pg/ml and 110±29 pg/ml, respectively, with significant difference (P = 0.015). The serum TRAIL levels after the surgery in these patients elevated to be similar to those detected in healthy controls (n = 52). The cause-specific survival rate of the RCC patients with high serum TRAIL was shown to be significantly higher than that of those with low serum TRAIL in the 5-year follow-up (P &amp;lt; 0.0385). The cytotoxicity of recombinant TRAIL and lymphocytes against human RCC cell line ACHN and primary culture RCC cell was measured by Crystal violet assay in the absence and presence of neutralizing anti-TRAIL antibody. TRAIL was estimated to contribute to about 20% of the lymphocyte-mediated cytotoxicity against ACHN and primary culture RCC cell. To our knowledge, the current study is the first to demonstrate the serum TRAIL levels of RCC patients in comparison with those of normal controls, in correlation with clinicopathological factors, and in association with postoperative prognosis. In conclusion, it is suggested that serum TRAIL levels in RCC patients might be utilized not only as diagnostic and prognostic biomarker but also as a possible biomarker for monitoring postoperative progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4644.