A serum mesothelin level is a prognostic indicator for patients with malignant mesothelioma in routine clinical practice

Abstract

BackgroundMalignant mesothelioma (MM) carries a poor prognosis and response rates to palliative chemotherapy remain low. Identifying patients with MM that are unlikely to respond to chemotherapy could prevent futile treatments and improve patient quality of life. Studies have suggested that soluble mesothelin is a potential biomarker for early diagnosis and prognosis of MM. We set out to explore the utility of serum mesothelin in routine clinical practice.MethodsWe conducted a prospective exploratory study of serum mesothelin levels in 53 consecutive patients with MM at our institution between April 2009 and February 2011. Survival was assessed and analysed by mesothelin level as both continuous and categorical variables using Cox regression models. Differences in response rate between treatment groups were assessed by the Kruskal-Wallis Test.ResultsAll 53 patients, who had been given study information agreed to participate. The patients’ median age was 69 (range 24–90). Median mesothelin level was 2.7 nM and this value was used to dichotomize categories: ≤2.7 nM (low) and >2.7 nM (high). The progression free survival (PFS) for low vs high mesothelin was 8.0 vs 5.1 months (HR 1.8, p-0.058). When mesothelin was accessed as a continuous variable for PFS the HR was 1.03 (95% CI: 1.01 - 1.06; p = 0.013). The overall survival (OS) for low vs high mesothelin was 17.2 vs 11.3 months (HR 1.9, p = 0.088). When mesothelin was assessed as a continuous variable for OS the HR was 1.02 (95% CI: 0.99 - 1.04; p = 0.073). Thirty patients received chemotherapy of which 18 had a pre-chemotherapy serum mesothelin level. In these 18 patients, the pre-chemotherapy mesothelin level did not correlate with response.ConclusionsA single random sample provides information about patient prognosis but does not predict treatment response. We suggest further prospective validation of mesothelin testing as a prognostic biomarker.

Midkine is a potential novel marker for malignant mesothelioma with different prognostic and diagnostic values from mesothelin

“…These studies indicated that increased serum levels of mesothelin were associated with disease progression and unresponsiveness to chemotherapy. Linch et al however demonstrated that the mesothelin levels before chemotherapy did not correlate with the responses [29]. We examined the relationship between baseline levels of all the evaluable cases and their chemotherapy responses, and found that the levels of both mesothelin and midkine markers were not associated with the responses.…”

Diagnosis and prognosis—review of biomarkers for mesothelioma

“…Several studies have shown no correlation between serum mesothelin level and progression-free or overall survival (7)(8)(9). On the other hand, some have shown that at cut off values of 1 and 3.5 nmol/L, SMRP levels are inversely associated with overall survival (10)(11)(12)(13). However, in multivariate analysis limited to epithelial MPM, the prognostic impact of SMRP on overall survival was lost.…”

Evaluation of soluble mesothelin-related peptides and MSLN genetic variability in asbestos-related diseases

“…12,14 Several studies also investigated SMRP as a prognostic biomarker in MM. 18,[21][22][23] SMRP levels were markedly increased at disease progression. 21 In a meta-analysis, increased SMRP was associated with shorter overall survival and worse prognosis.…”