Published online Jul 15, 2024. doi: 10.4251/wjgo.v16.i7.3069
Revised: May 5, 2024
Accepted: May 22, 2024
Published online: July 15, 2024
Processing time: 97 Days and 19.6 Hours
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. As liver cancer often presents no noticeable symptoms in its early stages, most patients are diagnosed at an advanced stage, complicating treatment. Therefore, the identification of new biomarkers is crucial for the early detection and treatment of HCC. Research on exportin-5 (XPO5) could offer new avenues for early diagnosis and improve treatment strategies.
To explore the role of XPO5 in HCC progression and its potential as a prognostic biomarker.
This study assessed XPO5 mRNA expression in HCC using The Cancer Genome Atlas, TIMER, and International Cancer Genome Consortium databases, correlating it with clinical profiles and disease progression. We performed in vitro experiments to examine the effect of XPO5 on liver cell growth. Gene Set Enrichment Analysis, Kyoto Encyclopedia of Genes and Genomes, and Gene Ontology were used to elucidate the biological roles and signaling pathways. We also evaluated XPO5’s impact on immune cell infiltration and validated its prognostic potential using machine learning.
XPO5 was significantly upregulated in HCC tissues, correlating with tumor grade, T-stage, and overall survival, indicating poor prognosis. Enrichment analyses linked high XPO5 expression with tumor immunity, particularly CD4 T cell memory activation and macrophage M0 infiltration. Drug sensitivity tests identified potential therapeutic agents such as MG-132, paclitaxel, and WH-4-023. Overexpression of XPO5 in HCC cells, compared to normal liver cells, was confirmed by western blotting and quantitative real-time polymerase chain reaction. The lentiviral transduction-mediated knockdown of XPO5 significantly reduced cell proliferation and metastasis. Among the various machine learning algorithms, the C5.0 decision tree algorithm achieved accuracy rates of 95.5% in the training set and 92.0% in the validation set.
Our analysis shows that XPO5 expression is a reliable prognostic indicator for patients with HCC and is sig
Core Tip: This study reveals the pivotal role of exportin-5 (XPO5), a miRNA transport protein, in the progression and prognosis of hepatocellular carcinoma (HCC). Bioinformatic databases and in vitro assays demonstrated that XPO5 expression was upregulated in HCC tissues, correlating with aggressive tumor features and poor patient outcomes. Furthermore, XPO5 levels influenced immune cell behavior, particularly in T cells and macrophages, suggesting its potential as a target for immunotherapy. This study suggests that XPO5 could be used as a biomarker for the prognosis of HCC and as a novel therapeutic target.