Abstract
PURPOSE: Systemic inflammatory response is reported to occupy a crucial role in the progression of hepatocellular carcinoma (HCC). The prognostic significance of SII and PNI in HCC has been explored, but the prognostic significance of aggregate index of systemic inflammation (AISI) in HCC is still unknown. This study was designed to determine the prognostic significance of AISI in HCC and explain the potential underlying mechanisms via gut microbiota and fecal metabolomic profiling. PATIENTS AND METHODS: A cohort of 109 cases of HCC individuals during January 2023 to August 2024 was included into this clinical research, and the clinical information and fresh fecal samples were collected. The fecal samples were collected for 16S rRNA sequence and metabolomics analysis. RESULTS: Survival analysis revealed that HCC patients in low AISI group tend to experience relatively longer survival time compared with those in high AISI group. Then, we employed ROC analysis to measure the predictive performance of AISI for the survival outcome, and ROC curve showed that levels of AISI had good predictive performance for the survival status with an AUC of 0.771 (95%CI: 0.671-0.871). 16S rRNA sequencing results revealed that levels of Parabacteroides were up-regulated in the low AISI group, and levels of Fusicatenibacter were up-regulated in the high AISI group. Metabolic analysis demonstrated that cavipetin A, pemptoporphyrin, and 8-Oxo-dGMP with high VIP value were the most distinct fecal metabolites. CONCLUSION: AISI is a potential prognostic biomarker in individuals with HCC. A low level of AISI was correlated with high abundance of Parabacteroides and some metabolites, indicating that AISI might affect the prognosis of HCC individuals via the regulations of gut microbes and metabolites.