bims-mesote 2026-07-19 papers

Issue of 2026–07–19
seven papers selected by
Laura Mannarino, Humanitas Research

Sci Rep. 2026 Jul 15.

Maintenance pemetrexed after platinum pemetrexed chemotherapy and survival outcomes in malignant pleural mesothelioma in a multicenter real world study.

Okan Aydin, Zehra Sucuoglu Isleyen, Mert Erciyestepe, Ahmet Emin Ozturk, Sermin Dinc Sonusen, Tugay Atasever, Simay Cokgezer, Ebru Cicek, Ayse Gul Satman Durmaz, Lamia Seker Can, Gozde Balkaya Aykut, Tuba Baydas, Miray Aydogan, Seval Ay Ersoy, Muhammed Mustafa Atci, Kayhan Erturk.

Malignant pleural mesothelioma (MPM) is an aggressive malignancy with poor prognosis, and the role of maintenance therapy after first-line platinum-pemetrexed chemotherapy remains unclear. We conducted a multicenter retrospective study including 96 patients with metastatic or unresectable MPM treated across eight tertiary oncology centers. Eligible patients had received at least four cycles of first-line platinum-pemetrexed and achieved disease control, after which they were either administered maintenance pemetrexed (n = 54) or observed without further treatment (n = 42). Maintenance pemetrexed was associated with significantly prolonged median progression-free survival (15.5 vs. 7.9 months; p < 0.001) and overall survival (22.3 vs. 16.4 months; p = 0.002) compared with observation. Multivariate analyses confirmed maintenance pemetrexed as an independent predictor of improved progression-free survival (HR 2.92; 95% CI 1.81-4.72; p < 0.001) and overall survival (HR 2.10; 95% CI 1.24-3.55; p = 0.005). Non-epithelioid histology was independently associated with worse outcomes. Subgroup analyses demonstrated that the survival benefit of maintenance pemetrexed persisted in patients achieving both partial response and stable disease after first-line chemotherapy. Importantly, maintenance therapy was well tolerated, with no discontinuations due to toxicity, highlighting its feasibility in routine practice. These real-world findings suggest that maintenance pemetrexed may be associated with improved survival outcomes in patients with MPM who achieve disease control after first-line therapy.

Keywords: Maintenance therapy; Malignant pleural mesothelioma; Pemetrexed; Platinum-based chemotherapy; Real-world study

DOI: https://doi.org/10.1038/s41598-026-61625-0

Front Oncol. 2026 ;16 1807528

Proliferation of pleural mesothelioma cells is enhanced by the microRNA-197-3p activity.

Ilaria Bononi, Giulia Di Mauro, Maria Letizia Tramarin, Valentina Esposito, Giulia Tonnini, Lucia Oton-Gonzalez, Beatrice Dallan, Elena Torreggiani, Fernanda Martini, Mauro Tognon.

Human Pleural Mesothelioma (HPM) is an aggressive asbestos-related tumor with limited treatment options and a poor prognosis. MicroRNAs (miRNAs), known to play key roles in the pathogenesis of HPM, have emerged as promising candidates for both diagnostic and therapeutic applications. Among them, miR-197-3p has been previously identified as dysregulated in sera from HPM patients and workers ex-exposed to asbestos fibers. To investigate the functional role of miR-197-3p, loss- and gain-of-function studies were performed in HPM cell lines and human mesothelial cells (HMC) using miR-197-3p-specific antagomiR and mimic. The effects of miR-197-3p modulation on cell proliferation, viability, migration, and apoptosis were evaluated. In addition, bioinformatics analyses were performed to identify potential miR-197-3p target genes, which were subsequently evaluated at both mRNA and protein levels. MiR-197-3p tested significantly upregulated in HPM cells. Its inhibition led to a marked reduction of the HPM cell proliferation, whereas its overexpression in HMC promoted a proliferative phenotype, supporting a potential role in cell growth regulation. Among the predicted targets, TGF-β1 and p120 showed modulation at the mRNA level, although protein-level changes were limited or only partially consistent. These findings suggest that miR-197-3p may contribute to HPM pathogenesis by promoting cell proliferation and influencing critical molecular pathways. However, the underlying molecular mechanisms remain to be fully elucidated, and the interaction with candidate targets, such as TGF-β1 and p120, should be considered putative. Further investigations, including functional and mechanistic validation in more representative experimental models, will be required to clarify the role of miR-197-3p in HPM pathobiology.

Keywords: biomarker; miR-197-3p; pleural mesothelioma; proliferation; target

DOI: https://doi.org/10.3389/fonc.2026.1807528

Transl Cancer Res. 2026 Jun 30. 15(6): 476

Divergent roles of PRR11 and HEPACAM in pleural mesothelioma: PRR11 as a prognostic biomarker and HEPACAM as a stage-associated gene with paradoxical expression.

Rong-Xin Zhao, Mei-Ling Zhang, Qian Wang, Kai-Hua Lu.

Background: Pleural mesothelioma (PM) is an aggressive malignancy with poor prognosis. While identifying drivers of tumor progression is critical, the molecular alterations specifically associated with T-stage advancement remain poorly understood. This study aimed to investigate genes linked to T-stage progression in PM using The Cancer Genome Atlas (TCGA) data, with a focus on the previously unreported roles of PRR11 and HEPACAM in this disease.
Methods: RNA-sequencing data and clinical information for 87 PM patients were obtained from the TCGA database. After excluding patients with missing survival data, 43 patients were included in the survival analysis. Differential expression analysis was performed between advanced (T3-T4) and early (T1-T2) T-stage tumors using DESeq2. Survival analysis was conducted using Kaplan-Meier curves and multivariate Cox proportional hazards models. Associations between gene expression and T stage were evaluated, and the correlation between PRR11 and HEPACAM was assessed using Spearman correlation analysis.
Results: A total of 116 differentially expressed genes (DEGs) were identified between T3-T4 and T1-T2 tumors. While PRR11 was the most significantly upregulated gene in the overall DEGs analysis (log2FC =5.87), its expression showed no significant difference when directly comparing T3-T4 to T1-T2 groups (P=0.44). However, in multivariate analysis, high PRR11 expression emerged as an independent prognostic factor for worse overall survival (OS) [hazard ratio (HR) =2.74, P=0.005]. In contrast, HEPACAM, identified as the most significantly downregulated gene in the DEG analysis (log2FC =-5.10), exhibited paradoxically higher expression in advanced T-stage tumors compared to early-stage tumors (P=0.01). HEPACAM expression showed no significant association with OS (log-rank P=0.3). Notably, a significant negative correlation was observed between PRR11 and HEPACAM expression (Spearman's ρ =-0.375, P=0.01).
Conclusions: This study reveals divergent roles for PRR11 and HEPACAM in PM. PRR11 is a robust independent prognostic biomarker, despite its lack of correlation with local tumor invasion as defined by T stage. HEPACAM demonstrates a complex, stage-dependent expression pattern, suggesting a potential context-dependent role in late-stage tumor biology. The inverse correlation between these genes may reflect opposing cellular programs in PM progression. These findings provide new insights into the molecular heterogeneity of PM and highlight the importance of integrating multiple analytical approaches when interpreting transcriptomic data.

Keywords: HEPACAM; PRR11; Pleural mesothelioma (PM); T stage; prognosis

DOI: https://doi.org/10.21037/tcr-2026-0657

Thorac Cancer. 2026 Jul;17(14): e70353

Interleukin 32 Expression in Mesothelioma.

Takuya Mikamo, Riko Niwa, Yuki Hanamatsu, Tamotsu Takeuchi.

BACKGROUND: Interleukin 32 (IL32) has context-dependent roles in carcinogenesis across cancer types. In this study, we examined IL32 in mesotheliomas.
METHODS: IL32 protein expression was evaluated by immunohistochemistry in 56 mesothelioma tissue microarray specimens and by immunoblot analysis in cultured mesothelioma cell lines. The functional roles of IL32 were examined through ectopic expression of IL32β and IL32θ isoforms in D-Meso-Sonobe cells with epithelial-mesenchymal plasticity and through siRNA-mediated IL32 downregulation followed by cell-detachment-induced apoptosis assays in epithelioid mesothelioma cells.
RESULTS: IL32 immunoreactivity was detected in 20 of 56 mesothelioma tissue specimens, including cytoplasmic staining in 20 of 39 epithelioid cases, whereas little or no immunoreactivity was found in 17 sarcomatoid cases. In immunoblot analysis, an IL32 protein band was detected in two cultured epithelioid mesothelioma cell lines (MPM-2 and TCC-Meso-1), but not in sarcomatoid MPM-1 cells. Two IL32 isoforms, IL32β and IL32θ cDNAs, were isolated from MPM-2 cells. Ectopic expression of IL32θ, but not IL32β, inhibited the morphological transition from epithelioid to sarcomatoid features in D-Meso-Sonobe mesothelioma cells with mesothelial-mesenchymal transition plasticity. Conversely, siRNA-mediated downregulation of IL32 increased cell detachment-induced apoptosis in MPM-2 and TCC-Meso-1 epithelioid mesothelioma cells. Moreover, IL32 suppressed expression of secreted protein acidic and rich in cysteine, which is an epithelial-mesenchymal transition-related protein in mesothelioma cells.
CONCLUSIONS: These findings indicate that IL32 is expressed in epithelioid mesothelioma and may contribute to mesotheliomagenesis.

Keywords: IL32; carcinogenesis; immunohistochemistry; mesothelioma

DOI: https://doi.org/10.1111/1759-7714.70353

Clin Exp Med. 2026 Jul 17.

Research progress on the regulation of mesothelioma driven by deubiquitinating enzyme BAP1.

Wan-Ting Xuan, Yao Dong, Si-Yuan Ma, Man Liu, Xiao-Qi Liu, Na-Na Yao, Lan-Xi Hu, Ling-Ling Shi, Lin Ma, Jing-Hui Bai, Bo Huang.

Mesothelioma is a highly aggressive malignancy that develops through the combined influence of several factors, including environmental exposure, genetic susceptibility, immune status, and aberrant activation or dysregulation of signaling pathways. The BAP1 gene, a tumor suppressor located at chromosome 3p21.1, plays a pivotal role in maintaining genomic stability by functioning as a deubiquitinating enzyme in critical processes such as DNA damage repair, cell cycle regulation, and chromatin remodeling. Its proper activity requires nuclear localization via the nuclear localization signal (NLS) domain. When BAP1 undergoes a truncation mutation, the NLS loses its function and the protein is retained in the cytoplasm; whereas missense mutations in the UCH domain, whilst not necessarily altering subcellular localisation, can directly lead to the loss of deubiquitinase activity, thereby promoting tumour development.Consequently, elucidating the signaling pathways governed by BAP1, designing targeted therapeutic strategies for BAP1-mutant cancers, and implementing preventive interventions in BAP1 mutation carriers represent urgent clinical and research priorities.

Keywords: BAP1; Deubiquitinating enzyme; Mechanistic research; Mesothelioma; Targeted therapy

DOI: https://doi.org/10.1007/s10238-026-02249-6