bims-mesote 2025-07-13 papers

Issue of 2025–07–13
three papers selected by
Laura Mannarino, Humanitas Research

Oncology. 2025 Jul 08. 1-14

Prognostic Value of the HALP Score in Metastatic Mesothelioma: A Retrospective Study.

Ozlem Dogan, Yakup Duzkopru, Tulay Eren.

BACKGROUND: Malignant mesothelioma is a rare but aggressive cancer with limited treatment options and poor prognosis. Hemoglobin, Albumin, Lymphocyte, Platelet(HALP) score , reflecting inflammation and nutritional status, is a potential prognostic marker in various cancers. Our study aims to investigate the prognostic value of the HALP score in mesothelioma.
METHODS: This retrospective study included 68 metastatic mesothelioma patients diagnosed between 2015-2023. Clinical and laboratory data were collected, and HALP scores were calculated at the time of metastasis. Patients were divided into HALP-low and HALP-high groups based on the median HALP score. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method, and prognostic factors were assessed using univariate and multivariate analyses.
RESULTS: The median HALP score was 24.85. The median OS for the entire cohort was 11,59 months. Patients with low HALP scores had significantly worse OS (7,81 months) compared to those with high HALP scores (16,36 months) (p=0.01). Similarly, median PFS was significantly shorter in the HALP-low group (7,29 months) compared to the HALP-high group (12,12 months) (p=0.02). In multivariate analysis, low HALP score (p=0.02) and de novo metastatic disease (p=0.01) remained independent prognostic factors for OS.
CONCLUSION: This study demonstrates that the HALP score is an independent prognostic biomarker in metastatic mesothelioma. Low HALP scores are associated with worse OS and PFS. Given its simplicity and cost-effectiveness, the HALP score may be a valuable tool for risk stratification and treatment decision-making in clinical practice.

DOI: https://doi.org/10.1159/000547271

Am J Med Genet A. 2025 Jul 10. e64176

First Report of BAP1-Associated Polyposis.

Angela L Jacobson, Maegan E Roberts, Lindsey Byrne, Jenna Wolfe, Peter P Stanich, Mohamed H Abdel-Rahman, Colin C Pritchard, Eric Q Konnick.

BAP1 Tumor Predisposition Syndrome (BAP1-TPDS) is caused by germline pathogenic variants in the BAP1 gene and has been associated with uveal melanoma, mesothelioma, cutaneous melanoma, renal cell carcinoma, and other benign cutaneous lesions. Adenomatous colon polyposis has not previously been reported as part of BAP1-TPDS. We report two patients with unexplained adenomatous oligopolyposis and germline BAP1 pathogenic variants. To determine if BAP1 had a role in polypogenesis, we performed somatic mutational analysis on multiple polyps from both patients (n = 8 total polyps tested). In every polyp tested, we found evidence of second BAP1 allele inactivation, including second somatic BAP1 mutations. Further, we did not detect any mutations in the commonly identified adenomatous polyposis pathway drivers, APC, CTNNB1, or other WNT/β-catenin. We did not detect somatic BAP1 mutations in any adenomatous polyps from patients without germline BAP1 pathogenic variants (n = 151 patients), highlighting the specificity of somatic BAP1 second hit mutations in BAP1 germline carrier polyps. Our findings strongly support that the polyps in these patients were caused by BAP1, and that adenomatous oligopolyposis is a part of the BAP1-TPDS tumor spectrum. Further work is needed to characterize the penetrance of this new BAP1-associated phenotype.

Keywords: BAP1 ; BAP1‐TPDS; adenomas; adenomatous polyposis; germline; polyps

DOI: https://doi.org/10.1002/ajmg.a.64176

Cell Death Discov. 2025 Jul 10. 11(1): 319

The transcriptomic fingerprint of cancer response to Tumor Treating Fields (TTFields).

Tumor Treating Fields (TTFields) therapy is an approved cancer treatment modality, based on non-invasive application of electric fields to the tumor region. Proteomic and cell biology methods revealed a versatile mechanism of action to be involved in the response to TTFields. In the current research we performed whole transcriptome analysis across tumor types to identify pan-cancer responses to TTFields. For this we collected samples from control and TTFields-treated human cancer cell lines of gastric cancer, pancreatic cancer, ovarian cancer, non-small cell lung carcinoma, pleural mesothelioma, and glioblastoma. The transcriptomic analysis supported previous reported effects: downregulation of pathways associated with cell cycle, cell growth, and proliferation; downregulation of DNA replication and the FA-BRCA DNA repair pathway; and upregulation of cellular responses to stress-senescence, autophagy, and apoptosis. Notably, previously unrecognized downstream effects of TTFields were revealed on cellular metabolism, with downregulation of protein and RNA metabolism, and upregulation of steroid biosynthesis. Additional DNA repair pathways were also found to be downregulated, including nucleotide excision repair, base excision repair, and mismatch repair. In conclusion, this study revealed similar response patterns to TTFields across different tumor types, re-enforcing some already pinpointed mechanisms, while revealing new mechanisms. Unlocking these new mechanisms may allow identification of potential new cancer treatments for application together with TTFields based on mechanistical compatibility.

DOI: https://doi.org/10.1038/s41420-025-02615-5