Soluble mesothelin related peptides: A potential biomarker for malignant pleural mesothelioma

Abstract

9532 Background: At this time there are no biomarkers that can monitor therapy or predict asbestos-related malignant pleural mesothelioma (MPM). Fujirebio Diagnostics, Inc. developed MESOMARK™ a quantitative dual-monoclonal ELISA for soluble members of a family of proteins expressed by mesothelial cells called soluble mesothelin related peptides (SMRP). We assessed whether (1) SMRP levels in sera and pleural effusions (PE) differed between MPM, non-MPM tumors, asbestos-exposed non-MPM individuals (ASB) and normal volunteers (NL), and (2) SMRP could predict recurrence of MPM after surgery. Methods: Archived frozen serum from 26 ASB, 50 NLs, 54 MPMs, and 14 non-MPMs, and PE from 30 NL, 20 non-MPM tumors, and 45 MPMs were analyzed by MESOMARK™. Blinded longitudinal serum samples (preoperative to 47 month range) from 16 patients having cytoreduction and identical adjuvant therapy were investigated for post surgery SMRP levels and correlation with computerized tomographic (CT) follow-up scans. One-way ANOVA with post-hoc Tamhane test was used for statistical analyses. ROC curves were constructed for the serum and PE groups. Results: Serum SMRP levels were equivalent between ASB (1.166, range 0.004–2.821 nM), and NL (1.222, range 0.216–3.430 nM), but were significantly different from MPM (17.275, range 0.219–278.356 nM, p = 0.003). Stage I MPMs had higher levels of serum SMRP than ASB (p=0.046). Comparing the ASB and NL combined to MPMs, ROC curve analysis revealed an AUC of 0.793 (95%CI: 0.705 to 0.880). No differences were seen in the PE SMRP levels between non-MPM tumors and NL (p=0.521), however, MPM PE SMRP (65.573 nM, range 0.421–255.166) was significantly increased compared to NL PE SMRP (18.997 nM, range 0.291–140.121, p=0.003). The AUC under the PE ROC curve was 0.742 (95%CI: 0.637 to 0.847). SMRP levels decreased in 13/16 patients immediately following surgery, and increased significantly and preceded detection by CT in 10/13 patients who subsequently displayed postoperative progression. Conclusions: These data establish SMRP as a promising marker for MPM, and studies to further refine and validate these data in larger cohorts should be initiated. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Fujirebio Diagnostics Fujirebio Diagnostics Fujirebio Diagnostics