Liu Lu, Hui Ruting, Zeng Tianyang, Yang Xuetao, Wu Qingchen, Yang Tao
Intensive Care Unit of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China.
Department of Rehabilitation Medicine, Chengdu First People's Hospital, Chengdu, 61007, People's Republic of China.
Int J Gen Med. 2022 May 3;15:4613-4623. doi: 10.2147/IJGM.S355889. eCollection 2022.
Malignant pleural mesothelioma (MPM) is a particularly fatal cancer with a median survival of less than one year. The value of single-agent checkpoint inhibitors is still obscure in MPM. We aim to reveal CUL4B prognostic role and immune infiltrates in MPM patients.
CUL4B expression profile and clinical information of malignant pleura mesothelioma individuals were collected from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) dataset. Quantitative real-time PCR (qRT-PCR) analysis measured CUL4B mRNA expression in epithelioid, biphasic, sarcomatoid, and normal pleural cell lines.
CUL4B expression elevated in MPM and had a high diagnostic value with AUC = 0.772. Additionally, our results showed that CUL4B high expression significantly correlated with poorer outcomes in MPM. Moreover, GSEA revealed 15 KEGG pathways enriched in the CUL4B high-expression group, and 22 were exhibited in the CUL4B low-expression group. Otherwise, our results showed that CUL4B was relevant to Wnt antagonistic factors (BARX2), Insulin-like growth factor binding protein 3 (IGFBP3), and Phosphatase and tensin homolog (PTEN). In addition, our results revealed that CUL4B expression was positively linked with four types of immune cells, whereas CUL4B expression was negatively linked with three types of immune cells. Additionally, our results showed that CUL4B expression regulates T helper cells, Tcm, and Th2 cells infiltration MPM microenvironment. Finally, our results identified CUL4B high expression in MPM cell line NCI-H2052 (epithelioid), MSTO-211H (biphasic), and NCI-H28 (sarcomatoid).
CUL4B is a valuable prognostic biomarker and a critical immune cell infiltration regulator in MPM.
恶性胸膜间皮瘤（MPM）是一种特别致命的癌症，中位生存期不到一年。单药检查点抑制剂在MPM中的价值仍不明确。我们旨在揭示CUL4B在MPM患者中的预后作用和免疫浸润情况。
从基因表达综合数据库（GEO）和癌症基因组图谱（TCGA）数据集中收集恶性胸膜间皮瘤个体的CUL4B表达谱和临床信息。通过定量实时PCR（qRT-PCR）分析测量上皮样、双向性、肉瘤样和正常胸膜细胞系中CUL4B mRNA的表达。
CUL4B在MPM中的表达升高，诊断价值较高，曲线下面积（AUC）=0.772。此外，我们的结果表明，CUL4B高表达与MPM患者较差的预后显著相关。此外，基因集富集分析（GSEA）显示，CUL4B高表达组中有15条京都基因与基因组百科全书（KEGG）通路富集，CUL4B低表达组中有22条。此外，我们的结果表明，CUL4B与Wnt拮抗因子（BARX2）、胰岛素样生长因子结合蛋白3（IGFBP3）和磷酸酶及张力蛋白同源物（PTEN）相关。此外，我们的结果显示，CUL4B表达与四种免疫细胞呈正相关，而与三种免疫细胞呈负相关。此外，我们的结果表明，CUL4B表达调节辅助性T细胞、中央记忆性T细胞（Tcm）和Th2细胞浸润MPM微环境。最后，我们的结果确定了CUL4B在MPM细胞系NCI-H2052（上皮样）、MSTO-211H（双向性）和NCI-H28（肉瘤样）中高表达。
CUL4B是MPM中有价值的预后生物标志物和关键的免疫细胞浸润调节因子。
