A novel gene signature based on Like-Smith family members-related genes for predicting the prognosis of hepatocellular carcinoma.

[BACKGROUND] Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related deaths globally. The Like-Smith (LSM) family members are involved in RNA metabolism and tumor progression, but their role in HCC remains unclear. This study aims to construct a novel signature based on LSM family members-related genes and explore its clinical value in HCC.

[METHODS] Molecular patterns related to LSM family members were identified through clustering analysis. Differential expression analysis was used to identify genes with potential prognostic significance. Multivariate Cox regression analysis was performed to construct a signature with The Cancer Genome Atlas (TCGA) cohort. The International Cancer Genome Consortium (ICGC) cohort served as external validation. Kaplan-Meier curves and receiver operating characteristic (ROC) curves were used to evaluate the predictive ability. Enrichment analysis, immune infiltration assessment, and single-cell RNA sequencing (scRNA-seq) data analysis were conducted to explore the underlying mechanisms.

[RESULTS] Two genes-paired-like homeodomain 2 () and chromogranin A ()-were ultimately identified as a novel signature for HCC. Based on the risk score derived from the signature, samples were divided into high- and low-risk groups. Results indicated that the high-risk group had significantly poorer overall survival in both TCGA and ICGC cohorts. The ROC curves demonstrated that the signature exhibits stable predictive accuracy. Enrichment analysis showed that the high-risk group was associated with tumor-related pathways. Differences in immune infiltration were observed between high- and low-risk groups. scRNA-seq analysis indicated that and were highly expressed in hepatocytes.

[CONCLUSIONS] The novel two-gene signature comprising and effectively predicts survival outcomes in HCC patients and is closely associated with tumor metabolism and immune regulation. This signature may serve as a valuable tool for prognostic evaluation and guiding personalized treatment strategies for HCC patients.