High Expression of SAMM50 Indicates Poor Clinical Prognosis in Hepatocellular Carcinoma and Represents a Potential Novel Biomarker.

Identifying diagnostic and prognostic biomarkers and therapeutic targets for hepatocellular carcinoma (HCC) is essential to improve risk stratification, guide individualized treatment, and enhance therapeutic efficacy.The expression of SAMM50 (Sorting and Assembly Machinery Component 50) was initially analyzed in publicly accessible curated genomic and proteomic databases, such as the Cancer Cell Line Encyclopedia, the Human Protein Atlas, and other HCC-specific repositories. This analysis revealed differential expression patterns between HCC and non-neoplastic liver tissue. Subsequently, clinicopathological data and tissue specimens were collected from 200 HCC patients who underwent treatment at our institution. The protein and transcript levels of SAMM50 were experimentally measured in paired HCC and adjacent non-tumorous tissues using immunohistochemistry (IHC) and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The association between SAMM50 expression and key clinicopathological features was further evaluated. Univariate and multivariate Cox proportional hazards analyses were performed to determine the independent prognostic value of SAMM50 expression in HCC. Based on these results, a reproducible and clinically applicable nomogram, supported by a forest plot, was constructed to facilitate prognostic prediction and support individualized therapeutic decision-making. Finally, in vitro and in vivo experiments were conducted to characterize the phenotypic alterations in HCC cells after SAMM50 knockdown, thereby confirming its involvement in critical oncogenic behaviors.This research demonstrated that the mRNA and protein levels of SAMM50 in HCC tissues were elevated compared to those in normal liver and adjacent tissues. Immunohistochemistry findings confirmed that SAMM50 protein levels were persistently higher in HCC tissues than in paired adjacent tissues. High expression of SAMM50 was correlated with unfavorable clinicopathological factors, encompassing pretreatment alpha-fetoprotein (AFP) levels, tumor size, T stage, American Joint Committee on Cancer (AJCC) stage, histological grade, and worse overall survival.Specifically, high expression of SAMM50 was linked to shorter overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS). Moreover, univariate and multivariate Cox analyses were conducted to investigate the association between SAMM50 expression and clinicopathological features in HCC patients and to identify independent prognostic factors. The area under the receiver operating characteristic (ROC) curve (AUC) for SAMM50 was 0.863, suggesting its potential as a diagnostic marker for HCC, though further validation in independent cohorts is needed. Silencing of SAMM50 inhibited HCC cell proliferation, migration, and invasion, promoted apoptosis in vitro, and suppressed HCC growth in vivo.This research demonstrates that SAMM50 shows potential diagnostic value for HCC, though this observation requires further validation in larger, independent, and prospective cohorts. The results of this study not only contribute to the evaluation of baseline data and risk stratification in HCC but also offer novel approaches for the development of precise treatment strategies and targeted therapies.