Predictive value of immunogenic cell death biomarkers HMGB1, sRAGE, and DNase in liver cancer patients receiving transarterial chemoembolization therapy
- 417 Downloads
Transarterial chemoembolization (TACE) therapy is an effective locoregional anticancer treatment for liver cancer patients. Serum biomarkers involved in immunogenic cell death may be valuable for early predicting therapy response and estimating prognosis. Sera of 50 prospectively and consecutively included hepatocellular carcinoma (HCC) patients, undergoing TACE therapy, were taken before and 24 h after TACE application. In these samples, soluble biomarkers involved in immunogenic cell death, and among them, high-mobility group box 1 (HMGB1), soluble receptor of advanced glycation end products (sRAGE), and DNase activity were measured. They were compared with radiological response to therapy. A total of 71 TACE therapies were evaluated, of which 32 were classified as “no progression,” and 39, as “progression.” While HMGB1 levels increased already 24 h after TACE, there was an early decrease of sRAGE and DNase activity. Pretherapeutic and 24-h values of sRAGE were significantly higher in the no progression group than those in the progression group. There was no difference with respect to treatment response for DNase and HMGB1. Soluble RAGE is a new parameter with predictive relevance in primary liver cancer patients undergoing TACE therapy.
KeywordsHepatocellular cancer Transarterial chemoembolization Immunogenic cell death HMGB1 RAGE DNase
We are very grateful for the committed support of Prof. Jüngst who died recently. We thank Dr. Waggershauser from the Institute of Radiology of the University Hospital Munich for the excellent technical assistance in the evaluation of CT and MRI imaging.
Conflicts of interest
- 12.Takayasu K, Arii S, Matsuo N, Yoshikawa M, Ryu M, Takasaki K, Sato M, Yamanaka N, Shimamura Y, Ohto M. Comparison of CT findings with resected specimens after chemoembolization with iodized oil for hepatocellular carcinoma. Am J Roentgenol. 2000;175:699–704.Google Scholar
- 24.Urbonaviciute V, Furnrohr BG, Meister S, Munoz L, Heyder P, De Marchis F, Bianchi ME, Kirschning C, Wagner H, Manfredi AA, Kalden JR, Schett G, et al. Induction of inflammatory and immune responses by HMGB1-nucleosome complexes: implications for the pathogenesis of SLE. J Exp Med. 2008;205:3007–18.PubMedCrossRefGoogle Scholar
- 28.Apetoh L, Ghiringhelli F, Tesniere A, Obeid M, Ortiz C, Criollo A, Mignot G, Maiuri MC, Ullrich E, Saulnier P, Yang H, Amigorena S, et al. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med. 2007;13:1050–9.PubMedCrossRefGoogle Scholar
- 34.Jiao L, Weinstein SJ, Albanes D, Taylor PR, Graubard BI, Virtamo J, Stolzenberg-Solomon RZ. Evidence that serum levels of the soluble receptor for advanced glycation end products are inversely associated with pancreatic cancer risk: a prospective study. Cancer Res. 2011;71:3582–9.PubMedCrossRefGoogle Scholar
- 35.Stötzer OJ, Fersching DIM, Salat C, Siegele B, Nagel D, Holdenrieder S. Prediction of response to neoadjuvant chemotherapy in breast cancer patients by circulating soluble HMGB1 and RAGE. Tumor Biol. 2012 (in press)Google Scholar
- 43.Ikai I, Arii S, Kojiro M, Ichida T, Makuuchi M, Matsuyama Y, Nakanuma Y, Okita K, Omata M, Takayasu K, Yamaoka Y. Reevaluation of prognostic factors for survival after liver resection in patients with hepatocellular carcinoma in a Japanese nationwide survey. Cancer. 2004;101:796–802.PubMedCrossRefGoogle Scholar