bims-mesote 2026-08-02 papers

Issue of 2026–08–02
seven papers selected by
Laura Mannarino, Humanitas Research

Clin Med Insights Oncol. 2026 ;20 11795549261472695

The Prognostic Significance of BRCA1-Associated Protein 1(BAP1) in Malignant Pleural Mesothelioma: A Systematic Review and Meta-Analysis.

Jiaojiao Hong, Xianzi Dai, Jiangxia Yuan, Chengyu Chen, Zhengxing Huo, Chunwei Xu, Qian Wang.

Background: Malignant pleural mesothelioma (MPM) originates from pleural mesothelial cells and represents a highly aggressive malignancy. Characterized by a prolonged latency period, poor survival prognosis, and non-specific clinical manifestations, MPM poses significant diagnostic and therapeutic challenges. BRCA-1-associated protein 1 (BAP1) is a nuclear deubiquitinating enzyme involved in chromatin regulation, homologous recombination, and programmed cell death. Although multiple studies have suggested that BAP1 loss or mutation holds prognostic significance in malignant pleural mesothelioma, this remains a matter of debate.
Methods: A meta-analysis was conducted using data from the Web of Science, PubMed, Embase, Cochrane, and CNKI up to October 21, 2025. We included studies involving patients with malignant pleural mesothelioma that assessed the prognostic significance of BAP1. These studies reported hazard ratios (HR) and 95% confidence intervals (CI) for median overall survival (mOS) and median progression-free survival (mPFS).
Results: A total of 14 articles meeting the inclusion criteria were identified, encompassing 1,835 patients. We conducted both univariate and multivariate analyses of mOS, revealing that BAP1 deletion or mutation consistently correlated with improved prognosis, with hazard ratios of 0.51 (95% CI, 0.45-0.58, P < 0.0001) and 0.62 (95% CI, 0.54-0.71, P < 0.0001), respectively. The values were statistically significant (P < 0.0001). Furthermore, analyses of mPFS continued to demonstrate that BAP1 deletion or mutation consistently correlated with improved prognosis (U: HR = 0.62, 95% CI = 0.39-0.99, P = 0.04; M: HR = 0.79, 95% CI = 0.51-1.24, P = 0.31), though this did not reach statistical significance. Sensitivity analyses confirmed the robustness of these findings, with minimal heterogeneity between studies.
Conclusion: BAP1 serves as a potential prognostic marker for MPM, with its deletion or mutation indicating a favourable prognosis for patients. However, whether it provides valuable insights for various treatment strategies, including immunotherapy, requires further clinical investigation to determine.

Keywords: BRCA-1-associated protein 1; malignant pleural mesothelioma; median overall survival; meta-analysis; prognostic significance

DOI: https://doi.org/10.1177/11795549261472695

Lung Cancer. 2026 Jul 28. pii: S0169-5002(26)00614-8. [Epub ahead of print]219 109553

Low baseline cGAS expression is associated with longer progression-free survival in patients with pleural mesothelioma.

Antoine Torchiat, Karina Silina, Arya Ashok Nair, Laura Viktoria Heeb, Isabelle Opitz, Anurag Gupta, Alessandra Curioni-Fontecedro.

INTRODUCTION: The cyclic GMP-AMP synthase (cGAS)/STING pathway, a central DNA-sensing mechanism, is known to activate anti-tumor immune response but may also promote tumor progression when chronically activated. Given the role of asbestos-induced chronic inflammation in pleural mesothelioma (PM), we investigated cGAS/STING expression and its association with treatment outcomes.
METHODS: We analyzed tissue microarrays from 190 PM patients using multiparameter immunofluorescence single-cell imaging. cGAS and STING expression were quantified in Calretinin+ tumor cells, Calretinin-CD8-DC-LAMP- cells, and CD8+ cells before and after chemotherapy. Associations with treatment response and survival were assessed.
RESULTS: In matched pre- and post-treatment samples, total cGAS+ cell frequency increased after chemotherapy, as did cGAS+ frequencies in Calretinin+ tumor cells, Calretinin-CD8-DC-LAMP- cells, and CD8+ cells after FDR correction, whereas STING+ cell frequency did not differ. Within the progressive-disease subgroup, significant paired increases were retained for total cGAS+ cells and Calretinin-CD8-DC-LAMP- cells. However, the magnitude of change did not differ significantly among patients with partial response, stable disease, or progressive disease. Low baseline total cGAS+ frequency and cGAS+ frequency in Calretinin-CD8-DC-LAMP- cells were associated with longer progression-free survival. In an exploratory analysis of the TCGA PM cohort, higher CGAS/MB21D1 transcript expression was associated with shorter overall survival in continuous Cox regression, whereas STING1 transcript expression was not significantly associated with overall survival when analyzed as a continuous variable.
CONCLUSIONS: Low baseline cGAS+ frequency, particularly in the Calretinin-CD8-DC-LAMP- compartment, was associated with longer progression-free survival in PM. These findings support further evaluation of cGAS as a candidate prognostic biomarker but do not establish cGAS as a predictor of chemotherapy response or as a causal driver of treatment resistance.

Keywords: Multiparameter immunofluorescence; Pleural mesothelioma; STING; cGAS

DOI: https://doi.org/10.1016/j.lungcan.2026.109553

Int J Mol Sci. 2026 Jul 09. pii: 6134. [Epub ahead of print]27(14):

Glycan Fingerprint of Malignant Pleural Mesothelioma.

Lovro Kavur, Thomas S Klarić, Nikol Mraz, Nina Šimunić-Briški, Dora Lalić, Gordan Lauc, Martin Martinić, Lovorka Batelja Vuletić, Marina Martinić Kavur, Sven Seiwerth, Ozren Gamulin.

Malignant pleural mesothelioma (MPM) is an aggressive pleural tumor associated with asbestos exposure. Poor clinical outcome of MPM is often driven by late-stage diagnosis due to non-specific clinical presentation, similarity to pleural lesions (e.g., inflammatory changes, metastatic adenocarcinoma), and limitations of current diagnostic methods. We employed Fourier transform infrared (FTIR) spectroscopy combined with convolutional neural networks (CNNs) to analyze formalin-fixed paraffin-embedded (FFPE) pleural tissue samples from patients with MPM, metastatic adenocarcinoma, pleural inflammation, and normal (healthy) pleura. Glycan analysis of FFPE normal pleura and MPM was performed using ultra-high-performance liquid chromatography (UPLC) and mass spectrometry (MS). Our FTIR-spectral analysis uncovered a strong spectral fingerprint of MPM that was especially apparent in the region typical for C-O and C-C stretches as well as local symmetry region typical for deformation vibrations of CH2 and C-OH groups, all appearing in carbohydrates. Our orthogonal validation of these findings through a targeted glycomics approach using UPLC confirmed that the MPM N-glycome exhibits a distinct fingerprint that distinguishes it from normal pleural tissue. Through utilization of MS for identifying the exact structures of differentially expressed N-glycan peaks, we also identified two high-mannose N-glycan structures that show a specific biomarker potential for MPM and need to be examined in future studies.

Keywords: CNN classification; FTIR spectroscopy; N-glycans; biomarkers; glycosylation; liquid chromatography; malignant pleural mesothelioma

DOI: https://doi.org/10.3390/ijms27146134

Ann Thorac Surg. 2026 Jul 25. pii: S0003-4975(26)00730-7. [Epub ahead of print]

Efficacy of Perioperative Platinum-Pemetrexed Chemotherapy Combined with Pleurectomy/Decortication for Pleural Mesothelioma.

Akifumi Nakamura, Masaki Hashimoto, Nobuyuki Kondo, Seiji Matsumoto, Ayumi Kuroda, Kyoshiro Takegahara, Takashi Kijima, Seiki Hasegawa, Soichiro Funaki.

BACKGROUND: The optimal timing of chemotherapy in multimodal treatment for pleural mesothelioma remains unclear. This study evaluated the efficacy of adjuvant chemotherapy (AC) following neoadjuvant chemotherapy (NAC) with platinum and pemetrexed, combined with pleurectomy/decortication.
METHODS: We retrospectively reviewed patients with resectable pleural mesothelioma who underwent NAC followed by pleurectomy/decortication with macroscopic complete resection between January 2012 and December 2024. Patients were categorized into AC and non-AC groups. After 1:1 propensity score matching, landmark analyses using 30 days after surgery as the landmark time point were performed to minimize immortal time bias. Disease-free survival and overall survival were analyzed using the Kaplan-Meier method and Cox proportional hazards models. Subgroup analyses were performed to identify populations benefiting from AC.
RESULTS: Among 275 patients who achieved macroscopic complete resection, 273 were analyzed after excluding two 30-day postoperative deaths; 196 received AC, and 77 did not. After matching and a median follow-up of 35.5 months, the AC group showed significantly longer disease-free survival (median, 16.0 vs. 11.2 months; HR, 0.57; 95% CI, 0.39-0.83; p = 0.0034) and overall survival (median, 51.6 vs. 23.0 months; HR, 0.49; 95% CI, 0.30-0.78; p = 0.0028). Subgroup analyses suggested greater disease-free survival benefit in patients with nodal involvement (ypN1 vs ypN0) and ypStage IB or higher disease (8th edition).
CONCLUSIONS: Postoperative AC following NAC and pleurectomy/decortication may improve survival in pleural mesothelioma, particularly in patients with ypStage IB or higher disease.

DOI: https://doi.org/10.1016/j.athoracsur.2026.07.005

Respirol Case Rep. 2026 Aug;14(8): e70704

Successful Diagnostic Confirmation of Malignant Pleural Mesothelioma With Extensive Pleural Adhesions Using Pleural Cryobiopsy Under Local Anaesthesia.

Shotaro Otaki, Mikito Suzuki, Kaito Yano, Tomohiro Imoto, Reiko Shimizu, Tsunekazu Hishima, Kazuo Nakagawa.

Local anaesthesia thoracoscopy using flex-rigid thoracoscope is useful for diagnosing pleural lesions, but it is generally not indicated in cases with extensive pleural adhesions. We report a case of malignant pleural mesothelioma (MPM) with extensive pleural adhesions that was safely diagnosed using pleural cryobiopsy under local anaesthesia. A 65-year-old man with a history of asbestos exposure presented with chest pain and significant weight loss. A very small amount of pleural effusion, narrowing of the left lower intercostal spaces on chest computed tomography (CT) and negative lung sliding sign on transthoracic echocardiography (TTE) indicated significant pleural adhesions. Considering the high risk of general anaesthesia, biopsy under minimally invasive local anaesthesia was chosen. Precise localization of the lesions using positron emission tomography-CT and TTE enables making the incision over the tumour. After minimal adhesion dissection, pleural cryobiopsy was performed and a definitive diagnosis of epithelial MPM was made.

Keywords: flex‐rigid thoracoscope; local anaesthesia thoracoscopy; malignant pleural mesothelioma; pleural adhesions; pleural cryobiopsy

DOI: https://doi.org/10.1002/rcr2.70704