Xing Rui, Gan Junyu, Mei Jie, Li Zhixiong, Xu Jing
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.
Front Immunol. 2025 Jul 3;16:1619387. doi: 10.3389/fimmu.2025.1619387. eCollection 2025.
Hepatic arterial infusion chemotherapy (HAIC) using the FOLFOX regimen has been explored for unresectable hepatocellular carcinoma (HCC) patients, yet predictive biomarkers are lacking. This study aimed to evaluate the potential of serum growth differentiation factor 15 (GDF15) as a biomarker for predicting therapeutic response and survival outcomes in HCC patients undergoing FOLFOX-HAIC.
Pretreatment serum samples were collected from patients with unresectable HCC who received FOLFOX-HAIC between October 2016 and January 2019. GDF15 levels were measured using enzyme-linked immunosorbent assay (ELISA). Associations between serum GDF15 levels and treatment response, overall survival (OS), progression-free survival (PFS), and clinical characteristics were analyzed.
A total of 150 patients were included in the study. The mean GDF15 level was 7.16 ng/mL (mean ± SEM: 7.16 ± 0.72; range: 0.39-53.55 ng/mL). High serum GDF15 levels were significantly associated with poorer treatment response, shorter OS (median: 21.1 vs 40.33 months, = 0.0081) and PFS (median: 13.93 vs 20.47 months, = 0.0125). Multivariate Cox proportional hazards analysis identified serum GDF15 as an independent predictor of PFS (HR, 1.521; 95% CI, 1.014-2.283; = 0.043). Additionally, elevated GDF15 was positively correlated with larger tumor size ( < 0.0001), presence of microvascular invasion ( = 0.026) and abnormal AST levels ( = 0.001).
Serum GDF15 represents a potential prognostic biomarker in patients with unresectable HCC undergoing FOLFOX-HAIC treatment and may help guide treatment stratification.
对于不可切除的肝细胞癌（HCC）患者，已探索使用FOLFOX方案进行肝动脉灌注化疗（HAIC），但缺乏预测性生物标志物。本研究旨在评估血清生长分化因子15（GDF15）作为预测接受FOLFOX-HAIC治疗的HCC患者治疗反应和生存结果的生物标志物的潜力。
收集2016年10月至2019年1月期间接受FOLFOX-HAIC治疗的不可切除HCC患者的治疗前血清样本。使用酶联免疫吸附测定（ELISA）测量GDF15水平。分析血清GDF15水平与治疗反应、总生存期（OS）、无进展生存期（PFS）和临床特征之间的关联。
本研究共纳入150例患者。GDF15的平均水平为7.16 ng/mL（平均值±标准误：7.16±0.72；范围：0.39 - 53.55 ng/mL）。血清GDF15水平高与较差的治疗反应、较短的OS（中位数：21.1对40.33个月，P = 0.0081）和PFS（中位数：13.93对20.47个月，P = 0.0125）显著相关。多变量Cox比例风险分析确定血清GDF15是PFS的独立预测因子（风险比，1.521；95%置信区间，1.014 - 2.283；P = 0.043）。此外，GDF15升高与更大的肿瘤大小（P < 0.0001）、微血管侵犯的存在（P = 0.026）和异常的AST水平（P = 0.001）呈正相关。
血清GDF15是接受FOLFOX-HAIC治疗的不可切除HCC患者的潜在预后生物标志物，可能有助于指导治疗分层。
