# Lactylation-related genes signature panel in hepatocellular carcinoma reveals the prognostic and therapeutic optimization

## TL;DR

This study identifies a gene signature linked to lactylation in liver cancer that predicts survival and treatment response.

## Contribution

A novel lactylation-related gene signature is developed for predicting prognosis and treatment response in hepatocellular carcinoma.

## Key findings

- High-LRGS group shows significantly reduced survival and lower response to immune checkpoint inhibitors.
- High-LRGS tumors are more sensitive to specific antitumor drugs like AZD5153 and vorinostat.
- The LRGS model provides a tool for precision therapy and prognosis in hepatocellular carcinoma.

## Abstract

Lactylation-related genes (LRGs) exert a significant influence on tumor progression and are critically involved in modulating responses to immune checkpoint inhibitors (ICIs). Leveraging a curated set of 332 LRGs derived from the literature, we identified prognosis-specific hepatocellular carcinoma (HCC) clusters through consensus clustering analysis. Using an integrated bioinformatics approach, we systematically evaluated differences in immune microenvironment infiltration, somatic mutations, copy number variations, and epigenetic modifications between the two tumor subtypes. We subsequently developed a lactylation-related genes signature (LRGS) and independently validated its prognostic efficacy in the TCGA cohort. Notably, the high-LRGS group exhibited significantly reduced overall survival(OS) and diminished response to ICIs. Conversely, the high-LRGS group demonstrated heightened sensitivity to several antitumor agents, including AZD5153, cediranib, foretinib, and vorinostat, relative to the low-LRGS group. Our findings establish a robust LRGS model, offering a clinically actionable tool for prognostic assessment and precision therapy in HCC.