[Exploration of biomarkers for the efficacy of anti-PD-1 immunotherapy in patients with gastric cancer peritoneal metastasis].

Abstract

Objective: To explore the prognosis of patients with gastric cancer peritoneal metastasis (PM) receiving programmed cell death-1 (PD-1) antibody therapy, and investigate the biomarkers that affect the prognosis of anti-PD-1 therapy. Methods: This restrospecific study collected the clinic-pathological data of 56 patients with peritoneal metastasis of gastric cancer who received first-line treatment in the Nanjing Drum Town Hospital from March 2020 to September 2023, among which 41 had received anti-PD-1 immunotherapy and 15 hadn't. The relationship between overall survival (OS) and anti-PD-1 immunotherapy was evaluated by Kaplan-Meier analysis. The relationship between baseline peripheral blood indicators and treatment response of patients with anti-PD-1 treatment was analyzed using unpaired t-test. Subsequently, the COX proportional risk regression model was used to explore the clinical prognostic factors that may affect anti-PD-1 immunotherapy by univariate and multivariate analysis. The clinical prognostic factors included baseline data and baseline peripheral blood indexes such as anti-PD-1 treatment lines, Eastern Cooperative Oncology Group performance status (ECOG PS), combined positive score (CPS), expression of human epidermal growth factor receptor 2 (Her-2), EBER status, pathological types, other metastatic lesions, ascites content before immunotherapy, with or without abdominal drainage during anti-PD-1 treatment, blood lipid indicators, inflammatory indicators, and tumor indicators. Results: Kaplan-Meier survival statistics showed similar OS (15.9 vs. 15.2 months, P=0.6002) in patients with anti-PD-1 therapy compared to those without anti-PD-1 therapy. Patients with baseline high-density lipoprotein (HDL) ≥0.97 mmol/L (n=22) demonstrated a significantly longer median OS compared to those with HDL<0.97 mmol/L (15.2 vs. 13.5 months; P=0.018). Similarly, the cohort with apolipoprotein A1 (ApoA1) levels ≥0.86 g/L (n=21) showed superior survival outcomes, with a median OS of 17.73 months versus 12.27 months in the ApoA1＜0.86 g/L group (n=20; P=0.006). In contrast, elevated baseline alpha-fetoprotein (AFP) levels (n=2) were associated with markedly reduced survival (median OS: 5.7 vs. 15.2 months in normal AFP group, n=37; P=0.005). Notably, elevated pretreatment ApoA1 levels correlated with enhanced immunotherapy response (P=0.038). Multivariate Cox regression analysis revealed that ApoA1 deficiency (≥0.86 g/L) independently predicted better OS following PD-1 antibody therapy (hazard ratio [HR], 0.35 [95% CI, 0.12-0.98]; P=0.046) in gastric cancer patients with PM. Conclusions: In our study, it is first proposed that ApoA1 could be a significant predictor of the survival advantages of immunotherapy in gastric cancer patients with PM.