bims-mesote 2024-09-22 papers

Issue of 2024–09–22
four papers selected by
Laura Mannarino, Humanitas Research

Cancer Gene Ther. 2024 Sep 12.

BAG2, MAD2L1, and MDK are cancer-driver genes and candidate targets for novel therapies in malignant pleural mesothelioma.

Luisa Bisceglia, Federica Morani, Lara Guerrieri, Eric Santoni-Rugiu, Pınar Çakılkaya, Cristian Scatena, Rosa Scarpitta, Lars H Engelholm, Niels Behrendt, Federica Gemignani, Stefano Landi.

Malignant pleural mesothelioma (MPM) is an aggressive cancer with a poor prognosis and the identification of novel druggable targets is urgently needed. In previous work, we identified 15 deregulated genes highly expressed in MPM tissues and correlated with a poor prognosis. Here, we validated these findings on an independent dataset of 211 MPM patients (EGA, EGAD00001001915) and on a panel of MPM cell lines. Furthermore, we carried out in vitro gene silencing followed by proliferation, cytotoxicity, caspase, and migration assays to define whether these targets could be cancer-driver genes. We ended up with three novel candidates (i.e., BAG2, MAD2L1, and MDK), whose encoded proteins could be exploited as druggable targets. Moreover, of novelty, immunohistochemistry analysis on tissues revealed that the overexpression of BAG2 and MAD2L1 could differentiate MPM from RMP patients. Furthermore, when we tested Neratinib (an inhibitor of MAD2L1) and iMDK (an inhibitor of MDK) we found that they are effective on MPM cells, in part phenocopying the effects of MAD2L1 and MDK gene silencing. In summary, in the present work, we report that BAG2, MAD2L1, and MDK are bona fide cancer-driver genes for MPM worth of further studies.

DOI: https://doi.org/10.1038/s41417-024-00805-4

Cochrane Database Syst Rev. 2024 Sep 18. 9 CD014720

Immunotherapy for advanced and recurrent malignant pleural mesothelioma.

Anna Karen Haugaard, Rita Saude Conde, Ana Rita J Maria, Abhijna Vithal Yergolkar, Karsten Juhl Jørgensen, Bruno Heleno.

OBJECTIVES: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effects of immune checkpoint inhibitors (single-agent or combination therapy) in people with advanced malignant pleural mesothelioma in a first-line or salvage setting.

DOI: https://doi.org/10.1002/14651858.CD014720

Heliyon. 2024 Sep 15. 10(17): e37414

Prognostic significance of LAT1 expression in pleural mesothelioma.

Ryo Taguchi, Kyoichi Kaira, Yu Miura, Tetsuya Umesaki, Atsuto Mouri, Hisao Imai, Hiroshi Kagamu, Masanori Yasuda, Yoshikatsu Kanai, Hiroyuki Nitanda, Hironori Ishida, Hirozo Sakaguchi.

Background: The L-type amino acid transporter (LAT1) exhibits significantly increased expression within tumor cells across various neoplasms. However, the clinical significance of LAT1 expression in patients with pleural mesothelioma (PM) remains unclear.
Methods: Eighty patients diagnosed with PM between June 2007 and August 2022, were eligible for this study. LAT1, alanine-serine-cysteine transporter 2 (ASCT2), Ki-67, and VEGFR2 were evaluated by immunohistochemistry. Inflammatory and nutritional indices were also correlated with different variables, including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), systemic immune-inflammation index (SII), prognostic nutritional index (PNI), advanced lung cancer inflammation index (ALI), and Glasgow prognostic score (GPS).
Results: LAT1 was highly expressed in 57.5 % of patients with PM. Among the 80 patients included in this study, 65 (81.3 %) received chemotherapy, either alone or followed by surgical resection, while 15 (18.7 %) opted for best supportive care. The level of LAT1 significantly correlated with cell proliferation and ASCT2. Factors such as performance status, histology, LAT1 expression, PNI, ALI, and GPS were significant prognostic indicators for progression-free survival (PFS), while Ki-67, LAT1, NLR, SII, PNI, ALI, and GPS were identified as significant predictors for overall survival (OS). LAT1 expression emerged as an independent prognostic factor for predicting PFS and OS in all patients, as well as in the subgroup of 65 patients receiving chemotherapy. Notably, high LAT1 expression proved to be a significant predictor of outcome, particularly in the subgroup with high PLR and SII.
Conclusion: LAT1 was a significant predictor of outcomes in patients with PM and was more predictive of worse outcomes in patients with high inflammatory and low nutritional status.

Keywords: Immunohistochemistry; LAT1; Malignant mesothelioma; Predictive marker; Prognosis

DOI: https://doi.org/10.1016/j.heliyon.2024.e37414

Cureus. 2024 Aug;16(8): e67118

Challenging the Norm: Occurrence of Synchronous Pleural and Peritoneal Mesothelioma in a Female Patient.

Surendar Reddy, Kavya M G, Rakesh Gattu, Alekya P, Manasa Kuthadi.

Here, we present a unique case involving a female patient in her 40s with synchronous malignant pleural and peritoneal mesothelioma, despite lacking a history of asbestos exposure. The patient's initial symptoms included dyspnoea, chest pain, cough, fever, appetite loss, and weight loss over a month. Clinical evaluation led to the identification of right-sided pleural effusion, prompting consideration of differential diagnoses, such as tubercular or malignant pleural effusion. A thoracoscopy-guided biopsy, followed by histopathological examination and immunohistochemical staining, confirmed the diagnosis of mesothelioma. Chemotherapy was initiated as part of the treatment plan. The prognosis for this condition is generally bad; however, unusual cases of extended survival have been documented. The complexities of our case underscore the critical necessity for a thorough and aggressive evaluation of pleural effusion cases to unveil rare underlying causes, such as mesothelioma.

Keywords: malignant pleural effusion; malignant pleural mesothelioma (mpm); medical thoracoscopy; peritoneal mesothelioma; pleural interventions

DOI: https://doi.org/10.7759/cureus.67118