Multi-omics analysis of the lactylation-driven microenvironment and non-invasive clinical translation in
Xiangyu Gan1, Ruizhi Gao1, Dongming Xie1
1Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, China.
Background:
Through integrated multi-omics strategy, this study aims to investigate the clinical value of a prognostic model derived from lysine lactylation (KLa) in hepatocellular carcinoma (HCC), thereby promoting its clinical translation.
Methods:
The key features for constructing lactylation-associated risk model were identified across the levels of KLa, protein and transcriptomic by integrating local cohort and public HCC cohorts. Immunohistochemistry and western blotting were performed to confirm the consistency between lactylation-associated risk and KLa modification level. Clinical and biological significance of lactylation-associated risk stratification was further characterized leveraging local cohort with public HCC cohort and single-cell sequencing. Finally, we explored the potential of ultrasound-based radiomics for non-invasive prediction of lactylation-associated risk.
Results:
Lactylation-associated risk model effectively stratified HCC patients based on recurrence-free survival and identified individuals with early postoperative recurrence. High-risk patients demonstrated elevated KLa modification level and clinical characteristics indicative of poor prognosis: microvascular invasion, tumor thrombus, high Ki-67, advanced TNM and BCLC stages. At single-cell resolution, the predominantly immunosuppressive tumor immune microenvironment and KLa-driven proliferative tumor phenotype in high-risk patients elucidate the underlying biological mechanisms of HCC progression. The integration of ultrasound-based radiomics and clinical features demonstrated superior potential for lactylation-associated risk non-invasive prediction compared to single clinical model.
Conclusion:
Lactylation-associated risk model not only provides an effective assessment of recurrence risk in HCC patients but also mirrors the intratumoral KLa modification level, holding significant clinical and tumor biological relevance. Furthermore, the joint model integrating ultrasound-based radiomics and clinical features demonstrates potential for non-invasive prediction of lactylation-associated risk.
