Kynurenine metabolism-related gene signature for prognostic stratification in hepatocellular carcinoma

Background: Hepatocellular carcinoma (HCC) remains a major global health burden with high mortality rates and limited therapeutic options. The identification of reliable biomarkers for early diagnosis and prognosis prediction is urgently needed. Kynurenine metabolism, a critical pathway in immune regulation and tumor progression, has been implicated in various cancers. However, its prognostic value in HCC has not been fully elucidated. This study aimed to develop a prognostic risk model based on kynurenine metabolism-related genes (KMRGs) for HCC patients.

Methods: Transcriptomic and clinical data of HCC patients were retrieved from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) databases. A prognostic risk model was established using least absolute shrinkage and selection operator (LASSO) and Cox regression analyses. Survival analysis and functional enrichment analysis were conducted to validate the predictive performance of the model and to investigate the underlying mechanisms. ALDH8A1 was ultimately identified as a target gene based on survival analysis, and its impact on tumor cell migration was assessed using the HCC cell line.

Results: A prognostic model based on seven KMRGs was established. The high-risk group exhibited significantly worse overall survival compared to the low-risk group. Functional enrichment analysis in high-risk patients highlighted significant enrichment in core biological processes, including spliceosome assembly and ribonucleoprotein complex biogenesis. Furthermore, a nomogram integrating the risk score and clinical pathological features was developed, demonstrating moderate predictive performance for HCC prognosis.

Conclusions: This study successfully constructed a prognostic risk model based on seven KMRGs, providing a valuable tool for predicting clinical outcomes in HCC patients. These findings highlight the potential role of kynurenine metabolism in HCC progression and offer new insights for future therapeutic strategies.