1.Expression and prognostic significance of KAP1 gene in malignant pleural mesothelioma
Wen MEI ; Xinmeng WANG ; Ruai LIU ; Wei XIONG ; Yepin ZHANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(4):258-267
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.
2.Expression and prognostic significance of KAP1 gene in malignant pleural mesothelioma
Wen MEI ; Xinmeng WANG ; Ruai LIU ; Wei XIONG ; Yepin ZHANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(4):258-267
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.
3.Expression and significance of autophagy-related gene 5 in human malignant pleural mesothelioma
Ruai LIU ; Boyong WANG ; Jinsong LI ; Yuanqian PU ; Min YU ; Wei XIONG
Journal of China Medical University 2024;53(8):673-679
Objective To explore the expression of autophagy-related gene 5(ATG5)in human malignant pleural mesothelioma(MPM)cells and tissues and analyze the correlation between ATG5expression and patient clinicopathological parameters and prognosis.Methods Real-time quantitative PCR and Western blotting were used to detect differences in ATG5 expression between normal human pleural mesothelial cells and MPM cells and between non-MPM pleural mesothelial tissues and MPM tissues.The Cancer Genome Atlas was used to analyze correlations between ATG5 expression and clinicopathological characteristics and prognosis of patients with MPM.A Cox proportional hazard model was constructed to analyze factors affecting the prognosis of patients with MPM.The Gene Expression Profiling Interactive Analysis database was used to evaluate the correlation between ATG5and MPM tumor markers and novel serum markers.Tumor Immune Estimation Resource was used to analyze correlations between ATG5 and MPM immune cell infiltration and key immune regulatory genes.Results ATG5 was highly expressed in MPM cells and tissues and positively correlated with tumor stage(P<0.05).High ATG5 expression indicated poor prognosis(P<0.05).ATG5expression was significantly associated with various MPM tumor markers(MTAP,SETD2,NF2,and FIB3)and novel serum markers(HMGB1,SMPR,THBS2,and KRAS)(P<0.05).ATG5was associated with immune cell infiltration in MPM(B cells,CD4+T cells,and macrophages)and expression of immune-related genes(CD28,CUL48B,CD166,and MMP14)(P<0.05).Conclusion ATG5 is upregulated in MPM and is associated with poor prognosis and immune cell infiltration.ATG5 could be a key biomarker for early screening,diagnosis,and prognostic assessment of MPM.