Nuclear Medicine Laboratory, Tangshan People's Hospital, Tangshan, China.
Sixth Department of Oncology, Tangshan People's Hospital, Tangshan, China.
Clin Res Hepatol Gastroenterol. 2023 Aug;47(7):102149. doi: 10.1016/j.clinre.2023.102149. Epub 2023 May 27.
Cell division cycle 42 (CDC42) facilitates immune escape and drug resistance towards immunotherapy in several malignancies. This prospective study aimed to explore the predictive value of serum CDC42 for immune checkpoint inhibitor (ICI)-treatment response and survival in advanced hepatocellular carcinoma (HCC) patients.
Thirty advanced HCC patients scheduled for ICI or ICI-based treatment were enrolled in this prospective study, whose serum CDC42 was determined via enzyme-linked immunosorbent assay before therapy initiation.
The median (interquartile range) of serum CDC42 level was 766.5 (605.0-1329.5) pg/mL. Serum CDC42 was related to increased tumor size but decreased programmed death-ligand 1 combined positive score (PD-L1 CPS). With respect to ICI or ICI-based treatment outcomes, elevated serum CDC42 was associated with decreased disease control rate, but did not link with objective response rate. Patients with high serum CDC42 (vs. low, cut by its median level) had shortened progression-free survival (PFS), while overall survival (OS) only disclosed a reduced trend (lacked statistical significance) in patients with high serum CDC42 (vs. low). In detail, the median (95%CI) PFS and OS were 3.0 (0.0-6.0) months and 11.7 (2.7-20.7) months in patients with high serum CDC42, while they were 11.1 (6.6-15.6) months and 19.3 (14.5-24.1) months in patients with low CDC42. After adjusted by multivariate cox regression analysis, high serum CDC42 (vs. low) was independently associated with shortened PFS, but not OS.
Elevated serum CDC42 possesses a potential value in predicting worse ICI or ICI-based treatment outcomes in advanced HCC.
细胞分裂周期蛋白 42(CDC42)促进了几种恶性肿瘤的免疫逃逸和对免疫治疗的耐药性。本前瞻性研究旨在探讨血清 CDC42 对晚期肝细胞癌(HCC)患者免疫检查点抑制剂(ICI)治疗反应和生存的预测价值。
本前瞻性研究纳入了 30 名计划接受 ICI 或基于 ICI 的治疗的晚期 HCC 患者,在治疗前通过酶联免疫吸附试验测定其血清 CDC42 水平。
血清 CDC42 水平的中位数(四分位距)为 766.5(605.0-1329.5)pg/mL。血清 CDC42 与肿瘤大小增加有关,但与程序性死亡配体 1 联合阳性评分(PD-L1 CPS)降低有关。关于 ICI 或基于 ICI 的治疗结果,升高的血清 CDC42 与疾病控制率降低有关,但与客观缓解率无关。与血清 CDC42 低水平(以中位数水平为界)相比,血清 CDC42 高水平的患者无进展生存期(PFS)更短,而总生存期(OS)仅在血清 CDC42 高水平的患者中显示出降低的趋势(无统计学意义)(与低水平相比)。具体而言,血清 CDC42 高水平(vs. 低水平)患者的中位(95%CI)PFS 和 OS 分别为 3.0(0.0-6.0)个月和 11.7(2.7-20.7)个月,而血清 CDC42 低水平患者分别为 11.1(6.6-15.6)个月和 19.3(14.5-24.1)个月。经过多变量 Cox 回归分析调整后,血清 CDC42 高水平(vs. 低水平)与 PFS 缩短独立相关,但与 OS 无关。
升高的血清 CDC42 在预测晚期 HCC 患者接受 ICI 或基于 ICI 的治疗效果不佳方面具有潜在价值。