PD-L1 and prognosis in patients with malignant pleural mesothelioma: a meta-analysis and bioinformatics study

Our plain-English summary of PD-L1 and prognosis in patients with malignant pleural mesothelioma: a meta-analysis and bioinformatics study, by L. Jin, W. Gu, X. Li, et al (Therapeutic Advances in Medical Oncology, 2020).

The study

• Authors: L. Jin, W. Gu, X. Li, L. Xie, L. Wang, Z. Chen
• Journal: Therapeutic Advances in Medical Oncology
• Published: 2020;12:1758835920962362
• Cited by: 25 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

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.

© The Author(s), 2020.

In plain English

This was a meta-analysis, which pooled results from earlier published studies, plus a check against a public genetic database. The authors included 16 studies, published 2014 to 2020, covering 1899 patients with malignant pleural mesothelioma. They asked whether high levels of PD-L1, a protein measured in tumor tissue, were linked to survival. Asbestos exposure was not analyzed. Across the 16 studies, high PD-L1 was associated with poorer overall survival (hazard ratio 1.53, 95% CI 1.28–1.83), although results varied considerably between studies. In the two studies (307 patients) reporting time until the disease progressed, the association was not statistically significant (HR 1.07, 95% CI 0.82–1.39). High PD-L1 was also associated with sarcomatoid or biphasic rather than epithelial tumors (odds ratio 4.32, 95% CI 2.16–8.64). In 86 patients from The Cancer Genome Atlas, high PD-L1 messenger RNA levels were linked to poorer overall survival (HR 2.069, 95% CI 1.136–3.769). The authors concluded that high PD-L1 is a significant prognostic factor for poor overall survival.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Systematic review and meta-analysis of published studies, done according to PRISMA guidelines. The authors also checked the results against data from The Cancer Genome Atlas (TCGA), the bioinformatics part of the study.
• Who was studied: 16 studies published 2014 to 2020, totaling 1899 patients with malignant pleural mesothelioma. The studies came from Australia, France, Spain, Canada, the USA, Switzerland, Italy and Japan, and were found in literature searches up to 9 April 2020. A further 87 mesothelioma patients came from the TCGA PanCancer Atlas dataset.
• Exposure: This study did not examine asbestos or any other exposure. It looked at PD-L1 protein levels in tumor tissue, measured by immunohistochemistry staining and sorted into high and low groups using a cut-off value. In the TCGA data, it looked at PD-L1 messenger RNA levels.
• Main results:
  • Across all 16 studies (1899 patients), high PD-L1 was associated with poorer overall survival: pooled HR 1.53, 95% CI 1.28–1.83, p less than 0.001. Heterogeneity between studies was significant (I2 = 63.4%), so a random-effects model was used.
  • Heterogeneity among the 16 studies for overall survival was significant.
  • For progression-free survival, only two studies (307 cases) gave data. The association with PD-L1 was not statistically significant: HR 1.07, 95% CI 0.82–1.39, p = 0.643.
  • In subgroup analyses of overall survival, the authors reported that high PD-L1 was significantly associated with poor overall survival regardless of sample size, treatment method or PD-L1 cut-off value.
  • In the subgroup of the two prospective studies (283 patients), the hazard ratio for overall survival was 1.21 (95% CI 0.92–1.59, p = 0.178), which was not statistically significant.
  • In five studies with 840 patients, high PD-L1 was associated with sarcomatoid plus biphasic tumor type compared with epithelial type: OR 4.32, 95% CI 2.16–8.64, p less than 0.001. Associations with the following were not significant:
• smoking: OR 1.06, 95% CI 0.56–2.05
• clinical stage: OR 1.17, 95% CI 0.76–1.81
• sex: OR 1.02, 95% CI 0.67–1.54
  • TCGA overall survival analysis of 86 patients (14 high PD-L1, 72 low PD-L1):
• High group: 13 died, median survival 6.08 months.
• Low group: 60 died, median survival 19.99 months.
• HR 2.069, 95% CI 1.136–3.769, p = 0.0175.
  • TCGA progression-free survival analysis of 84 patients (12 high PD-L1, 72 low PD-L1):
• Median progression-free survival was 10.26 months in the high group and 14.73 months in the low group.
• HR 1.205, 95% CI 0.572–2.539, p = 0.624, which was not statistically significant.
  • Begg's test found no significant publication bias: p = 0.964 for overall survival and p = 0.317 for progression-free survival.
• The authors' conclusion: The authors concluded that high PD-L1 expression is a significant prognostic factor for poor overall survival, but not for progression-free survival, in patients with malignant pleural mesothelioma. They stated that the TCGA data confirmed this, and suggested that PD-L1 levels could be used in the future to predict clinical outcomes.
• Limitations the authors state:
  • Heterogeneity among the included studies was significant. Study design, treatment methods and other factors may have contributed.
  • Non-English studies and studies with negative results were not included, which may have caused publication bias.
  • Most included studies came from the USA and Europe, which may limit how well the results apply to other regions.
  • Only two studies were available for the progression-free survival analysis, so its sample size was small.
  • Only one included study involved patients treated with immunotherapy (pembrolizumab).

Topics

Medical terms in this study, explained in our Lexicon: PD-L1, Prognosis, Pleural Mesothelioma, Meta-Analysis, Hazard Ratio, confidence interval, Overall Survival, Progression-Free Survival.

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