Jin Xin, Shi Haida, Li Zhi, Li Huixing, Ma Huanxian, Shi Xianjie
Medical School of Chinese PLA and Faculty of Hepato-Biliary-Pancreatic Surgery, The First Medical Center of PLA General Hospital, Beijing 100853, China.
Emergency Department of the Fourth Medical Center of PLA General Hospital, Beijing 100853, China.
J Oncol. 2022 Sep 30;2022:2717056. doi: 10.1155/2022/2717056. eCollection 2022.
A large number of cancer-related deaths in the world can be attributed to liver hepatocellular carcinoma (LIHC). The purpose of this study is to explore protein tyrosine phosphatase type IV A member 3 (/PRL-3) as a new and reliable biomarker to predict the prognosis of LIHC and determine the potential therapeutic targets or drugs that can be used for treating LIHC.
We included three LIHC datasets with clinical information and expression profiles from public databases. The expression level of was analyzed, and based on the results, the samples were divided into high- and low-expression groups. The Kaplan-Meier survival analysis method was used to determine the relationship between and prognosis. The enrichment differences among the functional pathways associated with the high- and low-expression groups were determined using the gene set enrichment analysis (GSEA) method. Five methods were used to determine the differences among the tumor microenvironment in the low- and high-expression groups. The sensitivity of the low- and high-expression groups toward different drug treatment methods was predicted by analyzing the Tumor Immune Dysfunction and Exclusion (TIDE) scores and determining the biochemical half-maximal inhibitory concentration (IC50).
The expression levels of the LIHC and adjacent samples were analyzed, and it was observed that the expression level of in tumor tissue was significantly higher than the expression level of the same gene in the adjacent samples. It was also inferred that it might be a cancer-promoting gene. It was concluded that high-expression results in a significantly poor prognosis. The high-expression group was significantly enriched in the tumor-related pathways, such as the PI3K-AKT signaling pathway. In addition, the results obtained by conducting immune infiltration analysis revealed a significant positive correlation between some immune scores and the gene . The drug KIN001-135 and gene were also found to correlate positively with each other. CP466722, Pyrimethamine, AKT inhibitor VIII, Embelin, Cisplatin, QS11, Bexarotene, and Midostaurin negatively correlated with associated with the three datasets. Moreover, the drugs Cisplatin, QS11, Midostaurin, and CP466722 were more sensitive toward the high-expression group than the low expression group. Significant differences were observed in these cases.
/PRL-3 is potentially associated with the progression, metastasis, and invasion of LIHC. The prognosis of LIHC patients is negatively impacted by the high-expression levels of the gene. The results indicate that /PRL-3 is an important prognostic factor for LIHC and is a new potential prognostic detection target. The discovery of the 8 drugs that were negatively associated with provided a new direction that can be developed in the future for the treatment of LIHC.
世界上大量与癌症相关的死亡可归因于肝细胞癌（LIHC）。本研究的目的是探索IV型蛋白酪氨酸磷酸酶成员3（/PRL-3）作为一种新的可靠生物标志物，以预测LIHC的预后，并确定可用于治疗LIHC的潜在治疗靶点或药物。
我们纳入了来自公共数据库的三个具有临床信息和表达谱的LIHC数据集。分析了 的表达水平，并根据结果将样本分为高表达组和低表达组。采用Kaplan-Meier生存分析方法确定 与预后的关系。使用基因集富集分析（GSEA）方法确定高表达组和低表达组相关功能通路之间的富集差异。采用五种方法确定低表达组和高表达组肿瘤微环境的差异。通过分析肿瘤免疫功能障碍和排除（TIDE）评分并确定生化半数最大抑制浓度（IC50），预测低表达组和高表达组对不同药物治疗方法的敏感性。
分析了LIHC及其相邻样本的表达水平，观察到肿瘤组织中 的表达水平显著高于相邻样本中同一基因的表达水平。还推断它可能是一个促癌基因。得出高表达导致预后明显较差的结论。高表达组在肿瘤相关通路中显著富集，如PI3K-AKT信号通路。此外，免疫浸润分析结果显示，一些免疫评分与该基因之间存在显著正相关。还发现药物KINOO1-135与基因 呈正相关。CP466722、乙胺嘧啶、AKT抑制剂VIII、紫铆因、顺铂、QS11、贝沙罗汀和米哚妥林与三个数据集相关的 呈负相关。此外，顺铂、QS11米哚妥林和CP466722对高表达组的敏感性高于低表达组。在这些情况下观察到显著差异。
/PRL-3可能与LIHC的进展、转移和侵袭有关。LIHC患者的预后受到该基因高表达水平的负面影响。结果表明，/PRL-3是LIHC的一个重要预后因素，是一个新的潜在预后检测靶点。发现与 呈负相关的8种药物为未来LIHC的治疗提供了一个可开发的新方向。
