Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Liver Research Project Center, Hiroshima University, Hiroshima, Japan.
J Gastroenterol. 2018 Jan;53(1):107-118. doi: 10.1007/s00535-017-1348-8. Epub 2017 May 4.
Biomarkers predicting the response to the anticancer treatment and prognosis in patients with advanced hepatocellular carcinoma (HCC) are required. Recently, high mobility group box 1 (HMGB1) was reported to promote HCC progression and be associated with poor prognosis for patients with HCC. The purpose of this study was to assess serum HMGB1 concentrations before and during sorafenib treatment or hepatic arterial infusion chemotherapy (HAIC) and to explore the ability of serum HMGB1 concentrations to predict prognosis.
Serum HMGB1 concentrations were measured in 71 and 72 patients with advanced HCC treated with sorafenib and HAIC, respectively, to assess their usefulness for prediction of the response to the treatment and prognosis.
Multivariate analysis identified high HMGB1 at 4 weeks (P = 0.001), high α-fetoprotein (AFP) at baseline (P = 0.025), tumor liver occupying rate (P = 0.009) and modified RECIST (mRECIST, P < 0.0001) as independent predictors of poor overall survival in sorafenib treatment. High HMGB1 at 4 weeks (P = 0.025), vascular invasion to the hepatic vein (Vv) (P = 0.009), mRECIST (P < 0.0001) and Child-Pugh B (P = 0.004) were identified as independent predictors of poor overall survival in HAIC treatment. The concentrations of HMGB1 at baseline and 4 weeks were not correlated with conventional tumor markers and progressive disease assessed by mRECIST at 8 weeks.
These results suggest that serum HMGB1 at 4 weeks after the start of treatment might be a useful biomarker with added value to the conventional tumor marker and radiologic responses to predict poor overall survival in patients with advanced HCC treated with sorafenib or HAIC.
需要生物标志物来预测晚期肝细胞癌（HCC）患者对癌症治疗的反应和预后。最近，高迁移率族蛋白 1（HMGB1）被报道可促进 HCC 进展，并与 HCC 患者的预后不良相关。本研究旨在评估接受索拉非尼治疗或肝动脉灌注化疗（HAIC）的晚期 HCC 患者治疗前后血清 HMGB1 浓度，并探讨血清 HMGB1 浓度预测预后的能力。
分别对 71 例和 72 例接受索拉非尼和 HAIC 治疗的晚期 HCC 患者进行血清 HMGB1 浓度测定，以评估其对治疗反应和预后预测的有用性。
多变量分析确定了治疗 4 周时 HMGB1 高（P=0.001）、基线时 α-甲胎蛋白（AFP）高（P=0.025）、肿瘤肝占位率（P=0.009）和改良 RECIST（mRECIST，P<0.0001）是索拉非尼治疗总生存期不良的独立预测因素。治疗 4 周时 HMGB1 高（P=0.025）、肝静脉血管侵犯（Vv）（P=0.009）、mRECIST（P<0.0001）和 Child-Pugh B（P=0.004）是 HAIC 治疗总生存期不良的独立预测因素。治疗开始后 4 周时 HMGB1 的基线浓度与常规肿瘤标志物和 8 周时 mRECIST 评估的进展性疾病不相关。
这些结果表明，治疗开始后 4 周时的血清 HMGB1 可能是一种有用的生物标志物，与常规肿瘤标志物和放射学反应相结合，可预测接受索拉非尼或 HAIC 治疗的晚期 HCC 患者总生存期不良。
