Hepatocellular carcinoma (HCC) represents a major contributor to cancer-associated mortality globally. Due to the frequently asymptomatic early course and high proportion of late-stage detection, patient outcomes remain unsatisfactory, underscoring the demand for innovative diagnostic markers and treatment approaches. This study was dedicated to characterizing expression profiles and evaluating the prognostic value of myristoylated alanine-rich C kinase substrate-like 1 (MARCKSL1) in HCC. Through integrated analysis of data from the TCGA-LIHC and GSE14520 cohorts alongside in vitro validation, we comprehensively assessed MARCKSL1 expression patterns and their links with clinicopathological parameters. Public cohort analyses showed that MARCKSL1 was significantly upregulated in HCC tissues, and qRT-PCR analysis further supported elevated MARCKSL1 expression in selected HCC cell lines. This upregulated MARCKSL1 expression showed a positive correlation with various poor prognostic clinical factors, namely advanced tumor stage, higher histological grade, and elevated alpha-fetoprotein (AFP) concentration. Moreover, elevated MARCKSL1 expression was linked to reduced overall survival (OS) and disease-specific survival (DSS). A prognostic model built on these observations demonstrated reliable performance in predicting patient survival. Functional annotation analyses implicated MARCKSL1 in essential processes including cell cycle control, and its expression showed a significant association with immune cell infiltration, indicating a potential connection to the tumor immune landscape. Additionally, MARCKSL1 expression correlated with m⁶A methylation markers, suggesting its potential implication in the correlative networks of these epigenetic pathways during HCC development. We also established a predictive competing endogenous RNA (ceRNA) network, identifying key long non-coding RNAs (lncRNAs) that may co-regulate MARCKSL1 via specific microRNAs. Preliminary in vitro assessment supported increased MARCKSL1 transcript expression in selected HCC cell lines. In summary, MARCKSL1 is overexpressed in HCC and closely tied to aggressive clinicopathological traits and inferior prognosis, offering new insights into the evaluation of candidate prognostic biomarkers for HCC.
Li et al. (2026) studied this question.