bims-mesote 2023-04-30 papers

bims-mesote

Biomed News

on Mesothelioma

Issue of 2023–04–30
seven papers selected by
Laura Mannarino, Humanitas Research

ATG5 as biomarker for early detection of malignant mesothelioma.
LncRNAs and related molecular basis in malignant pleural mesothelioma: challenges and potential.
Modern Malignant Mesothelioma Manifestation.
Diagnostic value of combination of biomarkers for malignant pleural mesothelioma: a systematic review and meta-analysis.
Prognostic significance of inflammation-related and electrolyte laboratory variables in patients with malignant pleural mesothelioma.
Caregivers of patients with malignant pleural mesothelioma: who provides care, what care do they provide and what burden do they experience?
Identification and Characterisation of Infiltrating Immune Cells in Malignant Pleural Mesothelioma Using Spatial Transcriptomics.

BMC Res Notes. 2023 Apr 24. 16(1): 61

ATG5 as biomarker for early detection of malignant mesothelioma.

Marco Tomasetti, Federica Monaco, Olga Strogovets, Luca Volpini, Matteo Valentino, Monica Amati, Jiri Neuzil, Lory Santarelli.

   OBJECTIVES: Malignant pleural mesothelioma (MPM) is an aggressive disease with grim prognosis due to lack of effective treatment options. Disease prediction in association with early diagnosis may both contribute to improved MPM survival. Inflammation and autophagy are two processes associated with asbestos-induced transformation. We evaluated the level of two autophagic factors ATG5 and HMGB1, microRNAs (miRNAs) such as miR-126 and miR-222, and the specific biomarker of MPM, soluble mesothelin related proteins (Mesothelin) in asbestos-exposed individuals, MPM patients, and healthy subjects. The performance of these markers in detecting MPM was investigated in pre-diagnostic samples of asbestos-subjects who developed MPM during the follow-up and compared for the three groups.
RESULTS: The ATG5 best distinguished the asbestos-exposed subjects with and without MPM, while miR-126 and Mesothelin were found as a significant prognostic biomarker for MPM. ATG5 has been identified as an asbestos-related biomarker that can help to detect MPM with high sensitivity and specificity in pre-diagnostic samples for up to two years before diagnosis. To utilize this approach practically, higher number of cases has to be tested in order to give the combination of the two markers sufficient statistical power. Performance of the biomarkers should be confirmed by testing their combination in an independent cohort with pre-diagnostic samples.

Keywords:  ATG5; Asbestos exposure; Biomarkers; HMGB1; Malignant pleural mesothelioma; miRNAs

DOI:  https://doi.org/10.1186/s13104-023-06330-1
Crit Rev Oncol Hematol. 2023 Apr 26. pii: S1040-8428(23)00100-2. [Epub ahead of print] 104012

LncRNAs and related molecular basis in malignant pleural mesothelioma: challenges and potential.

Xiaoling Xu, Huihui Li, Mingying Xie, Zichao Zhou, Ding Wang, Weimin Mao.

  Malignant pleural mesothelioma (MPM) is a rare but invasive cancer, which mainly arises from mesothelial tissues of pleura, peritoneum and pericardium. Despite significant advances in treatments, the prognosis of MPM patients remains poor, and the 5-year survival rate is less than 10%. Therefore, it is urgent to explore novel therapeutic targets for the treatment of MPM. Growing evidence has indicated that long non-coding RNAs (lncRNAs) potentially could be promising therapeutic targets for numerous cancers. In this regard, lncRNAs might also potentially therapeutic targets for MPM. Recent advances have been made to investigate the molecular basis of MPM. This review first provides a comprehensive overview of roles of lncRNAs in MPM and then discusses the relationship between molecular basis of MPM and MPM-related lncRNAs to implement them as promising therapeutic targets for MPM.

Keywords:  Long non-coding RNA; Malignant pleural mesothelioma; Therapeutic target

DOI:  https://doi.org/10.1016/j.critrevonc.2023.104012
Cureus. 2023 Mar;15(3): e36479

Modern Malignant Mesothelioma Manifestation.

Abrahim N Razzak, Ali Syed, Elizabeth R Procknow, Andrea Bequest, Pinky Jha.

  Malignant pleural mesothelioma (MPM) involves the uncontrolled growth of mesothelial cells that form the lining of pleural serous layers. MPM has been linked with asbestos exposure in mining and manufacturing occupations with an unforgiving prognosis of 4-18 months. In this case report, we present a 56-year-old male with a significant past medical history of hypertension, hyperlipidemia, hepatic steatosis, and ulcerative colitis who presented to the emergency department for worsening cough, eight-pound weight loss over the previous year, night sweats, and fatigue. The patient was admitted due to right pleural effusion with lower lobe collapse seen on imaging; upon diagnostic workup including pleural biopsy, results were consistent with malignant mesothelioma of the epithelioid type. Over the course of six months post-diagnosis, the patient underwent multiple hospital admissions due to acute hypoxic respiratory failure from the segmental left upper lobe and subsegmental right upper lobe pulmonary emboli, recurrent pleural effusion, and anemia. Given the aggressive nature of MPM, the patient was determined not to be a surgical candidate and underwent palliative chemotherapy sessions until his passing. As the patient worked in heating/ventilation/air conditioning with asbestos exposure, taking a full occupational history was crucial. MPM is relatively rare; however, the incidence has increased over the last decade due to tumor development lag time post-asbestos exposure and an increase in do-it-yourself projects. There is no cure for MPM. Multimodal treatment approaches with surgery, chemotherapy, radiotherapy, and immunotherapy have been noted in the literature.

Keywords:  hvac; industrial health; industrial workers; lung cancer; malignant pleural mesothelioma (mpm)

DOI:  https://doi.org/10.7759/cureus.36479
Front Oncol. 2023 ;13 1136049

Diagnostic value of combination of biomarkers for malignant pleural mesothelioma: a systematic review and meta-analysis.

Mucheng Zhu, Zhenhua Lu, Hao Guo, Xiaoting Gu, Defang Wei, Zhengyi Zhang.

   Introduction: Early-stage accurate diagnosis of malignant pleural mesothelioma (MPM) has always been a formidable challenge. DNA and protein as biomarkers for the diagnosis of MPM have received considerable attention, and yet the outcomes are inconsistent.
Methods: In this study, a systematic search employing PubMed, EMBASE, and Cochrane Library to identify relevant studies from the first day of databases to October 2021. Moreover, we adopt the QUADAS-2 to evaluate the quality of eligible studies and Stata 15.0 and Review Manager 5.4 software programs to perform the meta-analysis. Additionally, bioinformatics analysis was performed at GEPIA for the purpose of exploring relationship between related genes and the survival time of MPM patients.
Results: We included 15 studies at the DNA level and 31studies at the protein level in this meta-analysis. All results demonstrated that the diagnostic accuracy of the combination of MTAP + Fibulin-3 was the highest with the SEN 0.81 (95% CI: 0.67, 0.89) and the SPE 0.95 (95% CI: 0.90, 0.97). And the bioinformatics analysis indicated that the higher MTAP gene expression level was beneficial to enhance the survival time of MPM patients.
Discussion: Nonetheless, as a result of the limitations of the included samples, it may be necessary to conduct additional research before drawing conclusions.
Systematic review registration: https://inplasy.com/inplasy-2022-10-0043/, identifier INPLASY2022100043.

Keywords:  MPM; bioinformatics analysis; combination of DNA and protein; diagnostic; meta-analysis; prognosis

DOI:  https://doi.org/10.3389/fonc.2023.1136049
Front Med (Lausanne). 2023 ;10 1099685

Prognostic significance of inflammation-related and electrolyte laboratory variables in patients with malignant pleural mesothelioma.

Yuan Zhang, Jie Li, Shu Zhang.

   Objective: Malignant pleural mesothelioma (MPM) is a kind of pleural cancer characterized by low incidence but high invasiveness. There is heterogeneity in survival among patients with MPM. Inflammation-related and electrolyte laboratory variables were previously reported as potential predictors of survival. We evaluated the relationship between overall survival and pre-treatment biomarkers.
Materials and methods: Patients diagnosed with MPM in Beijing Chaoyang Hospital for more than 10 years were screened for this study. All basic, clinical, radiologic and laboratory variables were collected. The COX univariable and multivariable analysis were used to explore prognostic related risk factors.
Results: Ninety patients with MPM were included. The median follow-up of all patients was 57 months [interquartile range (IQR): 27-100 months]. The median survival time was 24 months (IQR: 12-52 months). Univariate survival analyses indicated that age, Eastern Cooperative Oncology Group Performance Status, treatment, erythrocyte sedimentation rate, calcium, lymphocyte, hemoglobin, platelet-to-lymphocyte ratio (PLR), and monocyte-to-white blood cell ratio (MWR) were significantly related to survival. Multivariable analysis demonstrated that age [hazard ratio (HR), 2.548; 95% confidence interval (CI) 1.145-5.666; p = 0.022], calcium (HR, 0.480; 95% CI 0.270-0.855; p = 0.013), PLR (HR, 2.152; 95% CI 1.163-3.981; p = 0.015), and MWR (HR, 3.360; 95% CI 1.830-6.170; p < 0.001) might have a significant impact on the prognosis.
Conclusion: Calcium, MWR, and PLR might be related to the prognosis of MPM patients. Analyzing the relationship between the results of inflammation-related and electrolyte laboratory variables in peripheral blood and prognosis could help clinicians evaluate the situation of patients.

Keywords:  calcium; malignant pleural mesothelioma; monocyte-to-white blood cell ratio; platelet-to-lymphocyte ratio; prognosis

DOI:  https://doi.org/10.3389/fmed.2023.1099685
Qual Life Res. 2023 Apr 25.

Caregivers of patients with malignant pleural mesothelioma: who provides care, what care do they provide and what burden do they experience?

Adam Moore, Bryan Bennett, Gavin Taylor-Stokes, Melinda J Daumont.

   PURPOSE: There are limited data on the impact of caregiving for patients with malignant pleural mesothelioma (MPM) on the caregiver. We aimed to identify the demographic characteristics of these caregivers, the caregiving activities they perform and how caregiving burden impacts their work productivity and overall activity.
METHODS: This cross-sectional study collected data from caregivers of patients with MPM across France, Italy, Spain and the United Kingdom January-June 2019. Caregiver demographics, daily caregiving tasks and the impact of caregiving on physical health was collected via questionnaire. The Zarit Burden Interview (ZBI) was used to assess caregiver burden and the Work Productivity and Activity Impairment questionnaire (WPAI) assessed impairment at work and during daily activities. Analyses were descriptive.
RESULTS: Overall, 291 caregivers provided data. Caregivers were mostly female (83%), living with the patient (82%) and their partner/spouse (71%). Caregivers provided over five hours of daily emotional/physical support to patients. ZBI scores indicated 74% of caregivers were at risk of developing depression. Employed caregivers had missed 12% of work in the past seven days, with considerable presenteeism (25%) and overall work impairment (33%) observed. Overall, the mean activity impairment was 40%.
CONCLUSION: Caregivers provide essential care for those with MPM. We show caregiving for patients with MPM involves a range of burdensome tasks that impact caregivers' emotional health and work reflected in ZBI and WPAI scores. Innovations in the management of MPM must account for how caregivers may be impacted and can be supported to carry out this important role.

Keywords:  Caregiver burden; Malignant; Mesothelioma; Patient care; Quality of life

DOI:  https://doi.org/10.1007/s11136-023-03410-4
Methods Protoc. 2023 Mar 28. pii: 35. [Epub ahead of print]6(2):

Identification and Characterisation of Infiltrating Immune Cells in Malignant Pleural Mesothelioma Using Spatial Transcriptomics.

Dmitrii Shek, Brian Gloss, Joey Lai, Li Ma, Hui E Zhang, Matteo S Carlino, Hema Mahajan, Adnan Nagrial, Bo Gao, Scott A Read, Golo Ahlenstiel.

  Increasing evidence strongly supports the key role of the tumour microenvironment in response to systemic therapy, particularly immune checkpoint inhibitors (ICIs). The tumour microenvironment is a complex tapestry of immune cells, some of which can suppress T-cell immunity to negatively impact ICI therapy. The immune component of the tumour microenvironment, although poorly understood, has the potential to reveal novel insights that can impact the efficacy and safety of ICI therapy. Successful identification and validation of these factors using cutting-edge spatial and single-cell technologies may enable the development of broad acting adjunct therapies as well as personalised cancer immunotherapies in the near future. In this paper we describe a protocol built upon Visium (10x Genomics) spatial transcriptomics to map and characterise the tumour-infiltrating immune microenvironment in malignant pleural mesothelioma. Using ImSig tumour-specific immune cell gene signatures and BayesSpace Bayesian statistical methodology, we were able to significantly improve immune cell identification and spatial resolution, respectively, improving our ability to analyse immune cell interactions within the tumour microenvironment.

Keywords:  immune checkpoint inhibitors; mesothelioma; research protocol; spatial analysis

DOI:  https://doi.org/10.3390/mps6020035