Significance of serum tumor necrosis factor-related apoptosis-inducing ligand as a prognostic biomarker for renal cell carcinoma

Toiyama,Daisuke; Takaha,Natsuki; Shinnoh,Masahide; Ueda,Takashi; Kimura,Yasunori; Nakamura,Terukazu; Hongo,Fumiya; Mikami,Kazuya; Kamoi,Kazumi; Kawauchi,Akihiro; Miki,Tsuneharu

doi:10.3892/mco.2012.35

Significance of serum tumor necrosis factor-related apoptosis-inducing ligand as a prognostic biomarker for renal cell carcinoma

Authors:
- Daisuke Toiyama
- Natsuki Takaha
- Masahide Shinnoh
- Takashi Ueda
- Yasunori Kimura
- Terukazu Nakamura
- Fumiya Hongo
- Kazuya Mikami
- Kazumi Kamoi
- Akihiro Kawauchi
- Tsuneharu Miki
View Affiliations

Affiliations: Department of Urology, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kyoto 602-8566, Japan, Department of Translational Cancer Drug Development, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kyoto 602-8566, Japan
Published online on: October 15, 2012 https://doi.org/10.3892/mco.2012.35
Pages: 69-74

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is endogenously expressed in immune cells and contributes to immunosurveillance for cancer. TRAIL induces apoptosis preferentially in various cancer cells, including renal cell carcinoma (RCC) cells. In this study, the serum TRAIL level was examined using an enzyme-linked immunosorbent assay in 52 healthy controls and in 84 RCC patients prior to surgery and its significance as a biomarker was evaluated. The median serum TRAIL level was lower in RCC patients compared to the healthy controls (55.9 vs. 103.1 pg/ml; P=0.019). RCC with lymph node metastasis (N1-2), distant metastasis (M1), stage III-IV, or microscopic venous invasion was associated with decreased serum TRAIL levels (P=0.032, 0.067, 0.020 and 0.011). When comparing serum TRAIL levels in the same RCC patients prior and subsequent to surgery (n=11), the levels were significantly higher after surgery (P=0.031). The cause‑specific survival rate was significantly higher in RCC patients with high serum TRAIL levels compared to those with low serum TRAIL levels (P=0.0451). TRAIL was estimated to contribute 64 and 13% of the lymphocyte-mediated cytotoxicity against human RCC ACHN and Caki-1 cells, respectively. These data suggest that the serum TRAIL level may be useful as a prognostic biomarker in RCC patients.

View Figures

View References

1.	Ashkenazi A and Dixit VM: Death receptors: Signaling and modulation. Science. 281:1305–1308. 1998.
2.	Wiley SR, Schooley K, Smolak PJ, et al: Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity. 3:673–682. 1995.
3.	Pan G, O’Rourke K, Chinnaiyan AM, et al: The receptor for the cytotoxic ligand TRAIL. Science. 276:111–113. 1997.
4.	Sheridan JP, Marsters SA, Pitti RM, et al: Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors. Science. 277:818–821. 1997.
5.	Pan G, Ni J, Wei YF, Yu G, Gentz R and Dixit VM: An antagonist decoy receptor and a death domain-containing receptor for TRAIL. Science. 277:815–818. 1997.
6.	Mulders P, Figlin R, de Kernion JB, et al: Renal cell carcinoma: Recent progress and future directions. Cancer Res. 57:5189–5195. 1997.
7.	Bex A, Haanen JB, Vyth-Dreese FA, Horenblas S and de Gast GC: Cytokine therapy response as a selection criterion for cytoreductive nephrectomy in metastatic renal clear-cell carcinoma of intermediate prognosis. Results and conclusions from a combined analysis. Urol Int. 80:367–371. 2008.
8.	Escudier B, Eisen T, Stadler WM, et al: Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 356:125–134. 2007.
9.	Hudes G, Carducci M, Tomczak P, et al: Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 356:2271–2281. 2007.
10.	Motzer RJ, Escudier B, Oudard S, et al: Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet. 372:449–456. 2008.
11.	Motzer RJ, Hutson TE, Tomczak P, et al: Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 356:115–124. 2007.
12.	Froehner M, Hakenberg OW and Wirth MP: Molecular therapy in urologic oncology. Urol Int. 79:1–7. 2007.
13.	Takeda K, Smyth MJ, Cretney E, et al: Critical role for tumor necrosis factor-related apoptosis-inducing ligand in immune surveillance against tumor development. J Exp Med. 195:161–169. 2002.
14.	Ashkenazi A, Pai RC, Fong S, et al: Safety and antitumor activity of recombinant soluble Apo2 ligand. J Clin Invest. 104:155–162. 1999.
15.	Oya M, Ohtsubo M, Takayanagi A, Tachibana M, Shimizu N and Murai M: Constitutive activation of nuclear factor-kappaB prevents TRAIL-induced apoptosis in renal cancer cells. Oncogene. 20:3888–3896. 2001.
16.	Walczak H, Miller RE, Ariail K, et al: Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo. Nat Med. 5:157–163. 1999.
17.	Zeng Y, Wu XX, Fiscella M, et al: Monoclonal antibody to tumor necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2) induces apoptosis in primary renal cell carcinoma cells in vitro and inhibits tumor growth in vivo. Int J Oncol. 28:421–430. 2006.
18.	Macher-Goeppinger S, Aulmann S, Tagscherer KE, et al: Prognostic value of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and TRAIL receptors in renal cell cancer. Clin Cancer Res. 15:650–659. 2009.
19.	Roux S, Apetoh L, Chalmin F, et al: CD4⁺CD25⁺ Tregs control the TRAIL-dependent cytotoxicity of tumor-infiltrating DCs in rodent models of colon cancer. J Clin Invest. 118:3751–3761. 2008.
20.	Tecchio C, Huber V, Scapini P, et al: IFNalpha-stimulated neutrophils and monocytes release a soluble form of TNF-related apoptosis-inducing ligand (TRAIL/Apo-2 ligand) displaying apoptotic activity on leukemic cells. Blood. 103:3837–3844. 2004.
21.	Tanaka H, Ito T, Kyo T and Kimura A: Treatment with IFNalpha in vivo up-regulates serum-soluble TNF-related apoptosis inducing ligand (sTRAIL) levels and TRAIL mRNA expressions in neutrophils in chronic myelogenous leukemia patients. Eur J Haematol. 78:389–398. 2007.
22.	Perik PJ, Van der Graaf WT, De Vries EG, et al: Circulating apoptotic proteins are increased in long-term disease-free breast cancer survivors. Acta Oncol. 45:175–183. 2006.