Serum cell division cycle 42 in advanced hepatocellular carcinoma patients: Linkage with clinical characteristics and immune checkpoint inhibitor-related treatment outcomes

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: Elevated serum CDC42 possesses a potential value in predicting worse ICI or ICI-based treatment outcomes in advanced HCC.