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Title: [Expression and prognostic significance of KAP1 gene in malignant pleural mesothelioma].
Author: Mei W, Wang XM, Liu RA, Xiong W, Zhang YP.
Journal: Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi; 2024 Apr 20; 42(4):258-267. PubMed ID: 38677988.
Abstract:
Objective: To explore the expression of KAP1 (KRAB-associated protein 1, KAP1) in Malignant pleural mesothelioma (MPM) based on the cancer genome atlas (TCGA) and clinical trials. And elucidate the correlation between the expression of KAP1 and the clinical pathological parameters of patients with MPM and its prognosis. Methods: In April 2022, Based on the second generation KAP1mRNA sequencing data and clinicopathological data of MPM patients downloaded from TCGA database, the correlation between KAP1mRNA expression and clinical parameters was analyzed, and the correlation between KAP1 protein expression and clinicopathological parameters and its prognostic value were analyzed based on Chuxiong data set cohort clinical samples. The expression of KAP1 mRNA in MPM samples and matched normal tumor adjacent tissues was detected by qRT-PCR, and the expression of KAP1 protein in MPM and normal pleural tissues was detected by immunohistochemistry and Westernblotting. To construct a Kaplan-Meier model to explore the effect of KAP1 expression on the prognosis of MPM patients, and to analyze the prognostic factors of MPM patients by Cox regression. Results: qRT-PCR and Western blotting detection showed that the expression levels of KAP1 gene in four different MPM cells (NCI-H28, NCI-H2052, NCI-H2452, and MTSO-211H) were significantly higher than those in normal pleural mesothelial cells Met-5A. qRT-PCR, Western blotting and IHC results demonstrated that the mRNA and protein expression levels of KAP1 in MPM tissues was significantly higher than that in matching normal mesothelial tissues, and the expression level of KAP1 protein was correlated with TP 53 protein expression levels and serum CEA levels (P<0.05) . The mRNA expression level was significantly correlated with the prognosis, The overall survival time of mesothelioma patients with high KAP1mRNA expression was significantly shorter (HR=3.7, Logrank P<0.001) . Tumor type, age and the mRNA expression were related to the prognosis of MPM patients (P<0.05) . Multivariate analysis showed that tumor type and KAP1 mRNA expression level were independent prognostic factors of MPM patients (P<0.05) . Conclusion: In this study, TCGA database and Chuxiong cohort experiment samples were used to collect the relevant information of KAP1 expression in malignant melanoma tissues. It was confirmed that KAP1 is highly expressed in MPM tissues. The mRNA expression level and pathological type are correlated with the prognosis of patients. 目的： 分析KRAB相关蛋白1（KAP1）在恶性胸膜间皮瘤（MPM）中的表达，研究其表达水平与MPM患者的临床特征及预后的关系。 方法： 于2022年4月，通过TCGA数据库中下载的MPM患者KAP1 mRNA二代测序数据及临床病理资料，分析KAP1 mRNA表达量与临床参数相关性；基于楚雄数据集队列临床样本分析KAP1蛋白表达量与临床病理参数的相关性及其预后价值。用qRT-PCR和Western blotting法分析人正常胸膜间皮细胞系Met-5A和MPM细胞系NCI-H28（上皮型）、NCI-H2052 （肉瘤型）、NCI-H2452（双相混合型）和MTSO-211H中KAP1 mRNA和蛋白质的表达水平；用免疫组化和Western blotting法检测KAP1蛋白在MPM组织及正常胸膜组织中的表达。构建Kaplan-Meier模型探讨KAP1表达量对MPM患者预后的影响，Cox多因素回归分析MPM患者的预后影响因素。 结果： NCI-H28、NCI-H2052、NCI-H2452和MTSO-211H细胞中KAP1基因表达水平均明显高于Met-5A细胞（P<0.05）。与正常胸膜组织比较，MPM组织中KAP1明显高表达（P<0.05），KAP1蛋白表达水平与TP53蛋白表达水平、血清CEA水平相关（P<0.05）。KAP1 mRNA表达水平与总体生存率明显相关，KAP1 mRNA高表达的间皮瘤患者总生存时间均明显缩短（HR=3.7，Logrank P<0.001）。肿瘤类型、年龄与KAP1 mRNA表达水平MPM患者生存预后有关（P<0.05）。多因素分析发现，肿瘤类型和KAP1 mRNA表达水平是影响MPM患者预后的独立因素（P<0.05）。 结论： KAP1在MPM组织中呈高表达，其表达水平与病理类型可能与患者预后相关。.

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