Identification of Potential Hub Genes and Therapeutic Drugs in Malignant Pleural Mesothelioma by Integrated Bioinformatics Analysis

Zhang, Xiangxin; Liu, Yang; Chen, Wei Wei; Kong, Ming Zhe

doi:10.1159/000510534

Cited by 9 publications

(6 citation statements)

References 70 publications

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“…BAP1 is a histone deubiquitination enzyme encoded by genes. BAP1 is an important tumor suppressor gene encoded in the 21.1 region of the short arm of chromosome 3 (17) and can significantly increase the stability of the KLF5 protein. Righi et al (18) established that the most commonly mutated genes in malignant mesothelioma genome research results are BAP1, NF2 and CDKN2A/B.…”

Section: Introductionmentioning

confidence: 99%

Clinical significance of 9P21 gene combined with BAP1 and MTAP protein expression in diagnosis and prognosis of mesothelioma serous effusion

Shi

Wang

et al. 2022

Biomed Rep

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The diagnostic value of the 9P21 gene determined using fluorescence in situ hybridization (FISH) combined with BRCA1-associated protein 1 (BAP1) and methylthioadenosine phosphorylase (MTAP) expression detection by immunohistochemistry, was investigated in serous effusion samples of malignant mesothelioma. A total of 70 serous disease samples with serous effusion were collected from June 2017 to June 2020. Following biopsy specimen pathological diagnosis, samples were divided into malignant mesothelioma and benign mesothelioma. Differential expression of BAP1 and MTAP genes were identified in mesothelioma and mesenchymal hyperplasia. The 9P21 gene fragment was lost in mesothelioma. The positive rates of FISH, BAP1 and MTAP in biopsy specimens were 98.00, 94.00 and 90.00%. The specificity of the three were 96.00, 85.71 and 77.27%, the sensitivity were 90.00, 95.92 and 93.75%, and the positive rate of the combined detection of the three was 93.33%. The positive rate of serous fluid samples detected by the three methods (9P21 FISH probe combined with BAP1 and MTAP expression detected immunohistochemically) was 96.00, 92.00 and 88.00%, the specificity were 90.00, 77.27 and 71.43%, the sensitivity was 96.00, 93.75 and 89.80%, and the positive rate of the three combined detections was 91.33%. It was demonstrated that there was a high consistency between serous fluid samples and biopsy samples. According to clinicopathological analysis, sex, age, lesion site, Ki67 had little association with the occurrence and development of malignant mesothelioma, while asbestos exposure history was closely associated to the occurrence of mesothelioma. A high level of BAP1 gene was positively associated with the prognosis of mesothelioma, while a high level of MTAP gene was negatively associated with the prognosis of mesothelioma (P<0.05). Therefore, 9P21 FISH probe combined with BAP1 and MTAP can be used as a new method for the detection of malignant mesothelioma, and provide an important basis for the early diagnosis of mesothelioma.

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Section: Introductionmentioning

confidence: 99%

Clinical significance of 9P21 gene combined with BAP1 and MTAP protein expression in diagnosis and prognosis of mesothelioma serous effusion

Shi

Wang

et al. 2022

Biomed Rep

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“…proved through bioinformatics that the survival rate of MPM cases in the KIF20A high expression group was significantly lower than that of the low expression group. In addition, as indicated by the analysis of Cox regression factors, as opposed to MPM cases in the low expression group, the high expression of the mentioned genes is a risk factor for prognosis ( 35 ). Furthermore, the present study proved that the survival time of MPM cases with high KIF20A expression was significantly shorter than that of the low expression group, complying with the results of this article.…”

Section: Discussionmentioning

confidence: 99%

Identification of glycolysis genes signature for predicting prognosis in malignant pleural mesothelioma by bioinformatics and machine learning

Xiao¹,

Huang²,

Zhang³

et al. 2022

Front. Endocrinol.

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BackgroundGlycolysis-related genes as prognostic markers in malignant pleural mesothelioma (MPM) is still unclear. We hope to explore the relationship between glycolytic pathway genes and MPM prognosis by constructing prognostic risk models through bioinformatics and machine learning.MethodsThe authors screened the dataset GSE51024 from the GEO database for Gene set enrichment analysis (GSEA), and performed differentially expressed genes (DEGs) of glycolytic pathway gene sets. Then, Cox regression analysis was used to identify prognosis-associated glycolytic genes and establish a risk model. Further, the validity of the risk model was evaluated using the dataset GSE67487 in GEO database, and finally, a specimen classification model was constructed by support vector machine (SVM) and random forest (RF) to further screen prognostic genes.ResultsBy DEGs, five glycolysis-related pathway gene sets (17 glycolytic genes) were identified to be highly expressed in MPM tumor tissues. Also 11 genes associated with MPM prognosis were identified in TCGA-MPM patients, and 6 (COL5A1, ALDH2, KIF20A, ADH1B, SDC1, VCAN) of them were included by Multi-factor COX analysis to construct a prognostic risk model for MPM patients, with Area under the ROC curve (AUC) was 0.830. Further, dataset GSE67487 also confirmed the validity of the risk model, with a significant difference in overall survival (OS) between the low-risk and high-risk groups (P < 0.05). The final machine learning screened the five prognostic genes with the highest risk of MPM, in order of importance, were ALDH2, KIF20A, COL5A1, ADH1B and SDC1.ConclusionsA risk model based on six glycolytic genes (ALDH2, KIF20A, COL5A1, ADH1B, SDC1, VCAN) can effectively predict the prognosis of MPM patients.

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“…We have found both TEK and ANGPT1 are downregulated in MPM. Zhang et al (2020) [12] showed that CXCL8/IL8, PPARG, ADIPOQ, and IL6 are upregulated in malignant pleural mesothelioma. But we have found from our analyses that these genes are downregulated in MPM.…”

Section: Discussionmentioning

confidence: 99%

“…These key genes can be used as biomarkers and can be utilized for early diagnosis, survival prediction, drug target identification, and drug response observation [5][6][7][8][9][10][11]. Bioinformatics analyses have been employed to identify important genes and pathways involved in the disease process of malignant pleural mesothelioma [12][13][14]. Bioinformatics approach has also identified upregulation of spliceosomal genes, especially SF3B1 [15] and haploinsufficiency of BAP1 gene [16] are associated with MPM.…”

Section: Original Articlementioning

confidence: 99%

A network-biology approach for identification of key genes and pathways involved in malignant peritoneal mesothelioma

2021

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Identification of Potential Hub Genes and Therapeutic Drugs in Malignant Pleural Mesothelioma by Integrated Bioinformatics Analysis

Cited by 9 publications

References 70 publications

Clinical significance of 9P21 gene combined with BAP1 and MTAP protein expression in diagnosis and prognosis of mesothelioma serous effusion

Clinical significance of 9P21 gene combined with BAP1 and MTAP protein expression in diagnosis and prognosis of mesothelioma serous effusion

Identification of glycolysis genes signature for predicting prognosis in malignant pleural mesothelioma by bioinformatics and machine learning

A network-biology approach for identification of key genes and pathways involved in malignant peritoneal mesothelioma

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