Prognostic significance of the lymphocyte-to-monocyte ratio in patients with malignant pleural mesothelioma

Background: The prognostic value of programmed death-ligand 1 (PD-L1) expression in patients with malignant pleural mesothelioma (MPM) has been controversial according to previous investigations. Therefore, we conducted a meta-analysis to assess the potential prognostic significance of PD-L1 expression in MPM. Methods: PubMed, Embase, Web of Science, Scopus, and the Cochrane Library were thoroughly searched for relevant original articles published before 9 April 2020. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) of overall survival (OS) and progression-free survival (PFS) were calculated. The results of the meta-analysis were verified using The Cancer Genome Atlas (TCGA) dataset. Results: In total 16 studies were included in our meta-analysis. A high PD-L1 expression was associated with a poor OS (HR = 1.53, 95% CI = 1.28–1.83, p < 0.001), but not a grave PFS (HR = 1.07, 95% CI = 0.82–1.39, p = 0.643) in MPM. Furthermore, the PD-L1 expression correlated with the sarcomatoid + biphasic type of MPM (odds ratio = 4.32, 95% CI = 2.16–8.64, p < 0.001). TCGA data indicated that PD-L1 was a significant prognostic factor for OS (HR = 2.069, 95% CI = 1.136–3.769, p = 0.0175), but not for PFS (HR = 1.205, 95% CI = 0.572–2.539, p = 0.624), which was in accordance with the results of the meta-analysis. Conclusion: A high PD-L1 expression is a significant prognostic factor for poor OS of patients with MPM. We therefore suggest that PD-L1 expression levels can be used to predict the clinical outcomes of patients with MPM in the future.

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DNA Methylation of FKBP5 as Predictor of Overall Survival in Malignant Pleural Mesothelioma

Cancers ◽

10.3390/cancers12113470 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3470

Author(s):

Giovanni Cugliari ◽

Chiara Catalano ◽

Simonetta Guarrera ◽

Alessandra Allione ◽

Elisabetta Casalone ◽

...

Keyword(s):

Dna Methylation ◽

Overall Survival ◽

Malignant Pleural Mesothelioma ◽

P Value ◽

Pleural Mesothelioma ◽

Lymphocyte To Monocyte Ratio ◽

High Incidence ◽

Aggressive Tumor ◽

Independent Marker ◽

The Relationship

Malignant pleural mesothelioma (MPM) is an aggressive tumor with median survival of 12 months and limited effective treatments. The scope of this study was to study the relationship between blood DNA methylation (DNAm) and overall survival (OS) aiming at a noninvasive prognostic test. We investigated a cohort of 159 incident asbestos exposed MPM cases enrolled in an Italian area with high incidence of mesothelioma. Considering 12 months as a cut-off for OS, epigenome-wide association study (EWAS) revealed statistically significant (p value = 7.7 × 10−9) OS-related differential methylation of a single-CpG (cg03546163), located in the 5′UTR region of the FKBP5 gene. This is an independent marker of prognosis in MPM patients with a better performance than traditional inflammation-based scores such as lymphocyte-to-monocyte ratio (LMR). Cases with DNAm < 0.45 at the cg03546163 had significantly poor survival compared with those showing DNAm ≥ 0.45 (mean: 243 versus 534 days; p value< 0.001). Epigenetic changes at the FKBP5 gene were robustly associated with OS in MPM cases. Our results showed that blood DNA methylation levels could be promising and dynamic prognostic biomarkers in MPM.

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