Humans ; Mesothelioma, Malignant ; Mesothelioma/genetics* ; Peritoneal Neoplasms/genetics* ; Mutation ; AMP-Activated Protein Kinase Kinases

Malignant mesothelioma (MM) is a long latency, poor prognosis and asbestos exposure related malignant disease. Long non-coding RNA (lncRNA) is a kind of RNA with a length of more than 200 nucleotides that does not encode protein. It plays an important role in epigenetic regulation, cell cycle regulation and cell differentiation regulation. Recent studies have shown that the abnormal expression or function of lncRNA is closely related to the diagnosis and prognosis of MM. In this paper, the lncRNA research on MM is reviewed to better understand the role of lncRNA in MM.
Asbestos ; Epigenesis, Genetic ; Humans ; Mesothelioma/genetics* ; Mesothelioma, Malignant ; Prognosis ; RNA, Long Noncoding/genetics*

OBJECTIVETo detect the somatic mutations in peritoneal mesothelioma with whole genome sequencing technique.

METHODSSurgically resected cancer and pericancerous tissue samples from one patient with peritoneal mesothelioma were obtained. The whole genome sequences of tumor tissue and pericancerous tissue were examined by the second generation sequencing technique and compared with reference sequences from human genome database.

RESULTSThere were 639 717 single nucleotide variations (Single Nucleotide Variation SNV) found in both tumor and pericancerous tissue cells; while 20 302 SNVs were unique for tumor cells and 2 185 SNVs unique for pericancerous tissue, but still 223 SNVs found in cancer and pericancerous tissue were differed from those in human genome database.

CONCLUSIONThe preliminary results indicate that merely comparing the gene sequences of cancer and pericancerous tissue samples in an individual with the human genome reference sequence can not accurately locate all somatic mutations in pathological cells. For those individualized diseases caused by random somatic mutations, it is suggested to sequence the whole genome at birth or at least to reserve a DNA sample at early age for both research and clinical needs.

Aged ; DNA Mutational Analysis ; Female ; Humans ; Mesothelioma ; genetics ; Mutation ; Peritoneal Neoplasms ; genetics ; Polymorphism, Single Nucleotide

Objective: To investigate the expression of CD24 gene in human malignant pleural mesothelioma (MPM) cells and tissues, and evaluate its relationship with clinicopathological characteristics and clinical prognosis of MPM patients. Methods: In February 2021, UALCAN database was used to analyze the correlation between CD24 gene expression and clinicopathological characteristics in 87 cases of MPM patients. The TIMER 2.0 platform was used to explore the relationship between the expression of CD24 in MPM and tumor immune infiltrating cells. cBioportal online tool was used to analyze the correlation between CD24 and MPM tumor marker gene expression. RT-qPCR was used to analyze the expressions of CD24 gene in human normal pleural mesothelial cell lines LP9 and MPM cell lines NCI-H28 (epithelial type), NCI-H2052 (sarcoma type), and NCI-H2452 (biphasic mixed type). RT-qPCR was performed to detect the expressions of CD24 gene in 18 cases of MPM tissues and matched normal pleural tissues. The expression difference of CD24 protein in normal mesothelial tissue and MPM tissue was analyzed by immunohistochemistry. A Kaplan-Meier model was constructed to explore the influence of CD24 gene expression on the prognosis of MPM patients, and Cox regression analysis of prognostic factors in MPM patients was performed. Results: The CD24 gene expression without TP53 mutation MPM patients was significantly higher than that of patients in TP53 mutation (P<0.05). The expression of CD24 gene in MPM was positively correlated with B cells (r(s)=0.37, P<0.001). The expression of CD24 gene had a positive correlation with the expressions of thrombospondin 2 (THBS2) (r(s)=0.26, P<0.05), and had a negative correlation with the expression of epidermal growth factor containing fibulin like extracellular matrix protein 1 (EFEMP1), mesothelin (MSLN) and calbindin 2 (CALB2) (r(s)=-0.31, -0.52, -0.43, P<0.05). RT-qPCR showed that the expression level of CD24 gene in MPM cells (NCI-H28, NCI-H2052 and NCI-H2452) was significantly higher than that in normal pleural mesothelial LP9 cells. The expression level of CD24 gene in MPM tissues was significantly higher than that in matched normal pleural tissues (P<0.05). Immunohistochemistry showed that the expressions of CD24 protein in epithelial and sarcoma MPM tissues were higher than those of matched normal pleural tissues. Compared with low expression of CD24 gene, MPM patients with high expression of CD24 gene had lower overall survival (HR=2.100, 95%CI: 1.336-3.424, P<0.05) and disease-free survival (HR=1.800, 95%CI: 1.026-2.625, P<0.05). Cox multivariate analysis showed that compared with the biphasic mixed type, the epithelial type was a protective factor for the prognosis of MPM patients (HR=0.321, 95%CI: 0.172-0.623, P<0.001). Compared with low expression of CD24 gene, high expression of CD24 gene was an independent risk factor for the prognosis of MPM patients (HR=2.412, 95%CI: 1.291-4.492, P=0.006) . Conclusion: CD24 gene and protein are highly expressed in MPM tissues, and the high expression of CD24 gene suggests poor prognosis in MPM patients.
Humans ; Mesothelioma, Malignant ; Mesothelioma/diagnosis* ; Lung Neoplasms/genetics* ; Pleural Neoplasms/diagnosis* ; Prognosis ; Biomarkers, Tumor/analysis* ; Extracellular Matrix Proteins ; CD24 Antigen/genetics*

Gene Deletion ; Genes, p16 ; Humans ; In Situ Hybridization, Fluorescence ; Mesothelioma ; diagnosis ; genetics ; Neoplasms ; diagnosis ; genetics ; Pleural Neoplasms ; diagnosis ; genetics

OBJECTIVETo explore the risk factors for mesothelioma so as to provide epidemiological evidences for prevention of this disease and for further study of its pathogenesis.

METHODSA 1:1 paired case-control study was carried out in which asbestos exposure, life style and histories of cancer in first-degree relatives of 23 patients who had mesothelioma were compared with those of controls.

RESULTSThe mean age of patients was 57.96 years with a latency period of 52 years. There were no significant differences in mean exposure age, mean exposure periods, and smoking, drinking habits between patients and controls. The mean cumulative exposure of patients was 37.2 x 10(5) f, which was significantly higher than that of controls (32.3 x 10(5) f, P = 0.005). The odds ratio increased with the cumulative exposure. The percentage of cancer in first-degree relative of patients (26.1%) was significantly higher than that of controls [(4.4%, P < 0.05), OR = 7.75 (95% CI: 0.85-71.43)].

CONCLUSIONThere may be a dose-response relationship between mesothelioma and asbestos exposure. A family history of cancer may be a risk factor for mesothelioma, or may indicate an increased susceptibility to mesothelioma under the same level of asbestos exposure.

Asbestos, Crocidolite ; adverse effects ; Case-Control Studies ; Environmental Exposure ; Family ; Humans ; Life Style ; Mesothelioma ; etiology ; genetics ; Middle Aged ; Pleural Neoplasms ; etiology ; genetics ; Risk Factors

OBJECTIVETo study the role of p16 gene mutation status as detected by fluorescence in-situ hybridization (FISH) and p16 protein expression as detected by immunohistochemistry in differential diagnosis of malignant mesothelioma and benign mesothelial hyperplasia.

METHODSp16 gene mutation status and protein expression were detected by FISH and immunohistochemistry respectively in 55 cases of pleural malignant mesothelioma and 30 cases of benign mesothelial hyperplasia.

RESULTSFISH study showed that the rate of p16 deletion in malignant mesothelioma (81.8%,45/55) was higher than that in benign mesothelial hyperplasia (3.3%,1/30). The difference was statistically significant (P<0.05). Immunohistochemical study showed that the rate of p16 protein expression in malignant mesothelioma (23.6%) was lower than that in benign mesothelial hyperplasia (76.7%). The difference was also statistically significant. The sensitivity and specificity of FISH in distinguishing between mesothelioma and reactive mesothelial hyperplasia were higher than those of immunohistochemistry.

CONCLUSIONSIn contrast to reactive mesothelial hyperplasia, p16 gene is deleted and p16 protein is not expressed in malignant mesothelioma. The sensitivity and specificity of FISH are higher than those of immunohistochemistry in the distinction.

Cyclin-Dependent Kinase Inhibitor p16 ; metabolism ; Diagnosis, Differential ; Epithelium ; pathology ; Genes, p16 ; Humans ; Hyperplasia ; diagnosis ; genetics ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Mesothelioma ; diagnosis ; genetics ; metabolism ; Mutation ; Pleura ; pathology ; Pleural Neoplasms ; diagnosis ; genetics ; metabolism ; Sensitivity and Specificity

OBJECTIVETo investigate whether simian virus 40 (SV40) was related to patients of malignant mesothelioma in China.

METHODSParaffin-embeded samples of 17 patients with malignant mesothelioma were collected. After isolation of DNA from paraffin blocks, polymerase chain reaction (PCR) analyses were performed using three different sets of primer for detection of SV40 large T antigen gene. These samples were also immunohistochemically evaluated for expression of SV40 TAg protein with two different anti-SV40 Tag (Pab101 and Ab-2).

RESULTSOnly one of the three primer pairs successfully amplified SV40 genome in three malignant mesothelioma samples. No immunopositive staining for SV40 TAg was found in any of the samples.

CONCLUSIONSThe study shows that malignant mesothelioma in China may be independent of SV40 infection.

Adult ; Aged ; Antigens, Viral, Tumor ; genetics ; metabolism ; China ; Female ; Host-Pathogen Interactions ; Humans ; Immunohistochemistry ; Male ; Mesothelioma ; pathology ; virology ; Middle Aged ; Polymerase Chain Reaction ; Polyomavirus Infections ; pathology ; virology ; Simian virus 40 ; genetics ; immunology ; physiology ; Tumor Virus Infections ; pathology ; virology ; Young Adult

12E7 Antigen ; Antigens, CD ; metabolism ; Cell Adhesion Molecules ; metabolism ; Diagnosis, Differential ; Fibrosarcoma ; metabolism ; pathology ; Heart Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Humans ; Male ; Mesothelioma ; genetics ; metabolism ; pathology ; Middle Aged ; Mucin-1 ; metabolism ; Oncogene Proteins, Fusion ; metabolism ; Pericardiectomy ; Pericardium ; pathology ; Sarcoma ; metabolism ; pathology ; Sarcoma, Synovial ; genetics ; metabolism ; pathology ; surgery ; Translocation, Genetic ; Vimentin ; metabolism

Mcl-1 and Bcl-xL, key anti-apoptotic proteins of the Bcl-2 family, have attracted attention as important molecules in the cell survival and drug resistance. In this study, we investigated whether inhibition of Bcl-xL influences cell growth and apoptosis against simultaneous treatment of resveratrol and clofarabine in the human malignant mesothelioma H-2452 cells. Resveratrol and clofarabine decreased Mcl-1 protein levels but had little effect on Bcl-xL levels. In the presence of two compounds, any detectable change in the Mcl-1 mRNA levels was not observed in RT-PCR analysis, whereas pretreatment with the proteasome inhibitor MG132 led to its accumulation to levels far above basal levels. The knockdown of Bcl-xL inhibited cell proliferation with cell accumulation at G2/M phase and the appearance of sub-G0/G1 peak in DNA flow cytometric assay. The suppression of cell growth was accompanied by an increase in the caspase-3/7 activity with the resultant cleavages of procaspase-3 and its substrate poly (ADP-ribose) polymerase, and increased percentage of apoptotic propensities in annexin V binding assay. Collectively, our data represent that the efficacy of resveratrol and clofarabine for apoptosis induction was substantially enhanced by Bcl-xL-lowering strategy in which the simultaneous targeting of Mcl-1 and Bcl-xL could be a more effective strategy for treating malignant mesothelioma.
Adenine Nucleotides/*pharmacology ; Antimetabolites, Antineoplastic/*pharmacology ; Apoptosis/*drug effects ; Arabinonucleosides/*pharmacology ; Caspase 3/metabolism ; Caspase 7/metabolism ; Cell Line, Tumor ; Cell Proliferation/drug effects ; G2 Phase Cell Cycle Checkpoints/drug effects ; Gene Knockdown Techniques ; Humans ; Leupeptins/pharmacology ; Lung Neoplasms/metabolism/pathology ; M Phase Cell Cycle Checkpoints/drug effects ; Mesothelioma/metabolism/pathology ; Myeloid Cell Leukemia Sequence 1 Protein/antagonists & inhibitors/genetics/metabolism ; RNA Interference ; RNA, Messenger/metabolism ; RNA, Small Interfering/metabolism ; Stilbenes/*pharmacology ; bcl-X Protein/antagonists & inhibitors/*genetics/*metabolism