bims-mesote Biomed News
on Mesothelioma
Issue of 2021–05–16
six papers selected by
Laura Mannarino, Humanitas Research
  1. Extrapleural Pneumonectomy versus Pleurectomy/Decortication for Malignant Pleural Mesothelioma.
  2. Metastasis-associated gene 1 (MTA1) enhances cisplatin resistance of malignant pleural mesothelioma by ATR-Chk1-mediated DNA repair.
  3. Comparison of Nuclear Grade, Necrosis, and Histologic Subtype Between Biopsy and Resection in Pleural Malignant Mesothelioma.
  4. CAR T-cell therapy for pleural mesothelioma: Rationale, preclinical development, and clinical trials.
  5. Combined Analysis of RNA Sequence and Microarray Data Reveals a Competing Endogenous RNA Network as Novel Prognostic Markers in Malignant Pleural Mesothelioma.
  6. Histopathological typing in diffuse malignant epithelioid mesothelioma: implication for prognosis and molecular basis.
  1. Ann Thorac Surg. 2021 May 07. pii: S0003-4975(21)00846-8. [Epub ahead of print]
    Extrapleural Pneumonectomy versus Pleurectomy/Decortication for Malignant Pleural Mesothelioma.
    Nicolas Zhou, David C Rice, Anne S Tsao, Percy P Lee, Cara L Haymaker, Erin M Corsini, Mara B Antonoff, Wayne L Hofstetter, Ravi Rajaram, Jack A Roth, Stephen G Swisher, Ara A Vaporciyan, Garrett L Walsh, Reza J Mehran, Boris Sepesi.
       BACKGROUND: Whether extrapleural pneumonectomy (EPP) or extended pleurectomy/decortication (P/D) is the optimal resection for malignant pleural mesothelioma (MPM) remains controversial. We therefore compared perioperative outcomes and long-term survival of patients who underwent EPP vs P/D.
    METHODS: Patients with the diagnosis of MPM who underwent either EPP or P/D from 2000 to 2019 were identified from our departmental database. Propensity score matching was performed to minimize potential confounders for EPP or P/D. Survival analysis was performed by the Kaplan-Meier method and Cox multivariable analysis.
    RESULTS: Of 282 patients, 187 (66%) underwent EPP and 95 (34%) P/D. Even with propensity score matching, perioperative mortality was significantly higher for EPP than for P/D (11% vs. 0%; P=0.031), when adjusted for perioperative mortality, median overall survival between EPP and P/D was 15 vs. 22 months, respectively (P=0.276). Cox multivariable analysis for the matched cohort identified epithelioid histology (hazard ratio [HR], 0.56; P=0.029), macroscopic complete resection (HR, 0.41; P=0.004), adjuvant radiation therapy (HR, 0.57; P=0.019), and more recent operative years (HR, 0.93; P=0.011)-but not P/D-to be associated with better survival. Asbestos exposure (HR, 2.35; P=0.003) and pathological nodal disease (HR, 1.61; P=0.048) were associated with worse survival.
    CONCLUSIONS: In a multimodality treatment setting, P/D and EPP had comparable long-term oncological outcomes, although P/D had much lower perioperative mortality. The goal of surgical cytoreduction should be macroscopic complete resection achieved by the safest operation a patient can tolerate.
    DOI:  https://doi.org/10.1016/j.athoracsur.2021.04.078
  2. Ann Transl Med. 2021 Apr;9(8): 670
    Metastasis-associated gene 1 (MTA1) enhances cisplatin resistance of malignant pleural mesothelioma by ATR-Chk1-mediated DNA repair.
    Caihua Xu, Yufeng Hu, Bin Chen, Dapeng Li, Rongrui Liang, Meng Shen, Mengyao Wu, Min Tao.
       Background: Malignant pleural mesothelioma (MPM) chemoresistance remains a challenge to oncologists. In our previous study, we demonstrated that the aberrant expression of metastasis-associated gene 1 (MTA1) is associated with carcinogenesis and metastasis in MPM. The aim of the present study was to investigate the mechanism of MTA1 and chemo-resistance in MPM.
    Methods: Western blotting and real-time polymerase chain reaction were used to analyze the protein and mRNA levels. A stable clone with a knockdown of MTA1 was generated with shRNA via lentivirus technology in MPM cell lines. Cell Counting Kit-8 assay and crystal violet assay were used to measure cell viability. Immunochemical staining was employed to detect MTA1 expression in MPM tissues. The cell cycle of MPM cells was determined by phosphohistone H3 staining and flow cytometric analysis.
    Results: The MTA1 protein was upregulated and enhanced cisplatin resistance in MPM. Cisplatin stabilized the expression of the MTA1 protein by inhibiting its ubiquitination, and MTA1 enhanced G2/M cell cycle delay and regulated and protected the tumor genome from chemotherapeutic drugs via participating in the phosphorylation of the ataxia telangiectasia mutated and rad3 related-checkpoint kinase 1 (ATR-Chk1) pathway.
    Conclusions: These data suggest that MTA1 enhances cisplatin resistance by ATR-Chk1-mediated DNA damage repairment and cisplatin stabilizes MTA1 expression via affecting on the ubiquitination pathway of MTA1 in MPM. Our findings indicate that MTA1 could serve as a novel therapeutic target to overcome chemoresistance in MPM.
    Keywords:  ATR-Chk1; Metastasis-associated gene 1 (MTA1); chemoresistance; malignant pleural mesothelioma (MPM)
    DOI:  https://doi.org/10.21037/atm-21-941
  3. Am J Clin Pathol. 2021 May 12. pii: aqab054. [Epub ahead of print]
    Comparison of Nuclear Grade, Necrosis, and Histologic Subtype Between Biopsy and Resection in Pleural Malignant Mesothelioma.
    Jefree J Schulte, David B Chapel, Richard Attanoos, Luka Brcic, Juliet Burn, Kelly J Butnor, Nina Chang, Heather Chen, Sanja Dacic, Marc De Perrot, Junya Fukuoka, Francoise Galateau-Salle, Theresa Godschachner, Kenzo Hiroshima, Sonja Klebe, Thomas Krausz, Leslie Litzky, Alberto M Marchevsky, Jeffrey Mueller, Kazuki Nabeshima, Andrew G Nicholson, Prodipto Pal, Anja C Roden, Sara Rorvig, Eric Santoni-Rugiu, Henry Tazelaar, Ming-Sound Tsao, Ann E Walts, Birgit Weynand, Yoshiaki Zaizen, Yu Zhi Zhang, Aliya N Husain.
       OBJECTIVES: Numerous studies on malignant mesothelioma (MM) highlight the prognostic importance of histologic subtype, nuclear grade, and necrosis. This study compares these parameters in paired biopsy and resection specimens of pleural MM.
    METHODS: Histologic subtype, percentage of epithelioid morphology, nuclear grade, and the presence or absence of necrosis were compared in 429 paired biopsies and resection specimens of pleural MM from 19 institutions.
    RESULTS: Histologic subtype was concordant in 81% of cases (κ = 0.58). When compared with resection specimens, epithelioid morphology at biopsy had a positive predictive value (PPV) of 78.9% and a negative predictive value (NPV) of 93.5%; sarcomatoid morphology showed high PPV (92.9%) and NPV (99.3%), and biphasic morphology PPV was 89.7% and NPV was 79.7%. Agreement of the percentage of epithelioid morphology was fair (κ = 0.27). Nuclear grade and necrosis were concordant in 75% (κ = 0.59) and 81% (κ = 0.53) of cases, respectively. Nuclear grade showed moderate (κ = 0.53) and substantial (κ = 0.67) agreement from patients with and without neoadjuvant therapy, respectively, and necrosis showed moderate (κ = 0.47 and κ = 0.60) agreement, respectively, in the same subsets of paired specimens.
    CONCLUSIONS: Paired biopsy-resection specimens from pleural MM show overall moderate agreement in pathologic parameters. These findings may help guide postbiopsy management and triage of patients with MM.
    Keywords:  Histology; Malignant mesothelioma; Nuclear grading
    DOI:  https://doi.org/10.1093/ajcp/aqab054
  4. Lung Cancer. 2021 May 05. pii: S0169-5002(21)00172-0. [Epub ahead of print]
    CAR T-cell therapy for pleural mesothelioma: Rationale, preclinical development, and clinical trials.
    Navin K Chintala, David Restle, Hue Quach, Jasmeen Saini, Rebecca Bellis, Michael Offin, Jason Beattie, Prasad S Adusumilli.
      The aim of adoptive T-cell therapy is to promote tumor-infiltrating immune cells following the transfer of either tumor-harvested or genetically engineered T lymphocytes. A new chapter in adoptive T-cell therapy began with the success of chimeric antigen receptor (CAR) T-cell therapy. T cells harvested from peripheral blood are transduced with genetically engineered CARs that render the ability to recognize cancer cell-surface antigen and lyse cancer cells. The successes in CAR T-cell therapy for B-cell leukemia and lymphoma have led to efforts to expand this therapy to solid tumors. Herein, we discuss the rationale behind the preclinical development and clinical trials of T-cell therapies in patients with malignant pleural mesothelioma. Furthermore, we highlight the ongoing investigation of combination immunotherapy strategies to synergistically potentiate endogenous as well as adoptively transferred immunity.
    Keywords:  Adoptive cell therapy; Locoregional delivery; Malignant pleural mesothelioma; Pleural cancers
    DOI:  https://doi.org/10.1016/j.lungcan.2021.05.004
  5. Front Oncol. 2021 ;11 615234
    Combined Analysis of RNA Sequence and Microarray Data Reveals a Competing Endogenous RNA Network as Novel Prognostic Markers in Malignant Pleural Mesothelioma.
    Weicheng Duan, Kang Wang, Yijie Duan, Xiuyi Chen, Xufeng Chu, Ping Hu, Bo Xiong.
      Malignant pleural mesothelioma (MPM) is a highly aggressive cancer with short survival time. Unbalanced competing endogenous RNAs (ceRNAs) have been shown to participate in the tumor pathogenesis and served as biomarkers for the clinical prognosis. However, the comprehensive analyses of the ceRNA network in the prognosis of MPM are still rarely reported. In this study, we obtained the transcriptome data of the MPM and the normal samples from TCGA, EGA, and GEO databases and identified the differentially expressed (DE) mRNAs, lncRNAs, and miRNAs. The functions of the prognostic genes and the overlapped DEmRNAs were further annotated by the multiple enrichment analyses. Then, the targeting relationships among lncRNA-miRNA and miRNA-mRNA were predicted and calculated, and a prognostic ceRNA regulatory network was established. We included the prognostic 73 mRNAs and 13 miRNAs and 26 lncRNAs into the ceRNA network. Moreover, 33 mRNAs, three miRNAs, and seven lncRNAs were finally associated with prognosis, and a model including seven mRNAs, two lincRNAs, and some clinical factors was finally established and validated by two independent cohorts, where CDK6 and SGMS1-AS1 were significant to be independent prognostic factors. In addition, the identified co-expressed modules associated with the prognosis were overrepresented in the ceRNA network. Multiple enrichment analyses showed the important roles of the extracellular matrix components and cell division dysfunction in the invasion of MPM potentially. In summary, the prognostic ceRNA network of MPM was established and analyzed for the first time and these findings shed light on the function of ceRNAs and revealed the potential prognostic and therapeutic biomarkers of MPM.
    Keywords:  biomarker; ceRNA; lncRNA; mesothelioma; microenvironment; overall survival
    DOI:  https://doi.org/10.3389/fonc.2021.615234
  6. Pathology. 2021 May 06. pii: S0031-3025(21)00093-3. [Epub ahead of print]
    Histopathological typing in diffuse malignant epithelioid mesothelioma: implication for prognosis and molecular basis.
    Fabien Forest, David Laville, Cyril Habougit, Margot Corbasson, Sophie Bayle-Bleuez, Claire Tissot, Pierre Fournel, Olivier Tiffet, Michel Péoc'h.
      The prognostic impact of tumour grading, cytological and architectural patterns and stromal features in diffuse pleural malignant epithelioid mesothelioma (MEM) has been partly studied but not correlated to molecular features. We performed a retrospective study on 92 MEM in our department in order to assess the prognostic role of architectural and stromal patterns, especially tumour to stroma ratio. Secondly, based on The Cancer Genome Atlas (TCGA) database, we analysed the differentially expressed genes in prognostic groups of interest. Our results showed that tumour grading, tumour to stroma ratio and predominant pattern were related to overall survival, p≤0.001, p=0.01 and p=0.001, respectively. In univariate analysis, for high grade tumours hazard ratio (HR) was 4.75 (2.47-9.16), for stroma poor tumours HR=0.016, for predominant tubular or tubulopapillary pattern HR=0.044. In multivariate analysis, high grade tumours were related to overall survival [HR=3.09 (1.50-6.35), p=0.002] and predominant tubular or tubulopapillary pattern [HR=0.56 (0.32-0.99), p=0.045]. In TCGA analysis, after grading of diagnostic slides, we showed that KRTDAP and CXRCR1 expression was higher in low grade tumours, unlike PDZD7 and GPR176 expression which was higher in high grade tumours. FAM81B had a higher expression in stroma poor tumours. We did not find any differentially expressed genes in the architectural patterns group. Our work suggests that tumour grading is an important parameter in MEM with an underlying genomic basis. The role of tumour to stroma ratio needs to be investigated and might also have a genomic basis.
    Keywords:  Mesothelioma; grading; prognosis; solid pattern; tumour to stroma ratio
    DOI:  https://doi.org/10.1016/j.pathol.2021.01.010
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