Li Hao, Li Fei, Wang Bo-Shen, Zhu Bao-Li
Key Laboratory of Environmental Medicine Engineering of Ministry of Education, Southeast University, Nanjing 210000, Jiangsu Province, China.
Institute of Occupational Disease Prevention, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210000, Jiangsu Province, China.
World J Gastrointest Oncol. 2024 Jul 15;16(7):3069-3081. doi: 10.4251/wjgo.v16.i7.3069.
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 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 significantly associated with immune cell infiltration.
肝细胞癌（HCC）是全球癌症相关死亡的第三大主要原因。由于肝癌在早期通常没有明显症状，大多数患者在晚期才被诊断出来，这使治疗变得复杂。因此，鉴定新的生物标志物对于肝癌的早期检测和治疗至关重要。对核输出蛋白5（XPO5）的研究可为早期诊断提供新途径并改善治疗策略。
探讨XPO5在肝癌进展中的作用及其作为预后生物标志物的潜力。
本研究使用癌症基因组图谱、TIMER和国际癌症基因组联盟数据库评估肝癌中XPO5 mRNA的表达，并将其与临床特征和疾病进展相关联。我们进行实验以研究XPO5对肝细胞生长的影响。基因集富集分析、京都基因与基因组百科全书和基因本体论用于阐明其生物学作用和信号通路。我们还评估了XPO5对免疫细胞浸润的影响，并使用机器学习验证其预后潜力。
XPO5在肝癌组织中显著上调，与肿瘤分级、T分期和总生存期相关，表明预后不良。富集分析将高XPO5表达与肿瘤免疫联系起来，特别是CD4 T细胞记忆激活和巨噬细胞M0浸润。药物敏感性测试确定了潜在的治疗药物，如MG-132, 紫杉醇和WH-4-023。通过蛋白质免疫印迹法和定量实时聚合酶链反应证实，与正常肝细胞相比，肝癌细胞中XPO5过表达。慢病毒转导介导的XPO5敲低显著降低了细胞增殖和转移。在各种机器学习算法中，C5.0决策树算法在训练集中的准确率为95.5%，在验证集中的准确率为92.0%。
我们的分析表明，XPO5表达是肝癌患者可靠的预后指标，并且与免疫细胞浸润显著相关。
