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Mesothelin and osteopontin as circulating markers of diffuse malignant peritoneal mesothelioma: A preliminary study
Federica Bruno1, Dario Baratti1, Antonia Martinetti2
1Peritoneal Malignancy Program, National Cancer Institute, via Venezian, 1, 20133, Milan, Italy.
Background:
The differential diagnosis between diffuse malignant peritoneal mesothelioma (DMPM) and other peritoneal surface malignancies (PSM) is still challenging. Serum mesothelin and osteopontin are increasingly used as markers of pleural mesothelioma, but their role in DMPM is unclear. We assessed the diagnostic and prognostic values of mesothelin, osteopontin, CEA, CA19.9, CA125, and CA15.3 in DMPM patients.
Methods:
Markers were dosed before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) by enzyme-linked immunosorbent assay (ELISA) in 30 DMPM patients and 14 controls with other PSMs. Receiver-operating characteristics (ROC) curve were plotted. The performance of each marker was assessed by the area under the ROC curve (AUC-ROC).
Results:
Mean mesothelin levels were 7.84 ng/dl (SD = 5.14) in DMPM group and 3.00 ng/dl (SD = 1.25) in controls (P = 0.001). Mean CEA levels were 5.3 ng/dl (SD = 4.7), and 61.96 ng/dl (SD = 112.5) in the two groups (P = 0.008). No statistical difference was seen for osteopontin (P = 0.738), CA19.9 (P = 0.081), CA125 (P = 0.600), and CA15.3 (P = 0.365). AUC-ROC was 0.836 for CA19.9, 0.812 for mesothelin, 0.793 for CEA, and lower for CA125 (0.652), osteopontin (0.531), and CA15.3 (0.481). Using diagnostic cut-offs selected by ROC methodology, sensitivity, specificity, positive and negative predictive values were 70.0%, 100.0%, 100.0%, and 60.9% for mesothelin >5.21 ng/dl, and 90.0%, 85.7%, 93.1%, and 80.0% for CA19.9 < 8.8 U/dl. At multivariate analysis, osteopontin correlated with survival (hazard rate 6.46; 95%CI 1.81-23.05; P = 0.004).
Conclusion:
When assessing PSMs of unknown origin, elevated mesothelin with low CA19.9 may increase the suspicion index for DMPM. Ospeopontin warrants further investigations as a prognostic marker for DMPM.
Insights
Elevated serum mesothelin and low CA19.9 may help diagnose diffuse malignant peritoneal mesothelioma (DMPM). Osteopontin shows potential as a prognostic marker for DMPM, warranting further research.
Area of Science:
- Oncology
- Biomarker Research
- Surgical Oncology
Background:
- Distinguishing diffuse malignant peritoneal mesothelioma (DMPM) from other peritoneal surface malignancies (PSM) remains a diagnostic challenge.
- The diagnostic and prognostic roles of serum markers like mesothelin and osteopontin in DMPM are not well-established.
- This study investigates the utility of several serum markers for DMPM diagnosis and prognosis.
Purpose of the Study:
- To evaluate the diagnostic performance of serum mesothelin, osteopontin, CEA, CA19.9, CA125, and CA15.3 in differentiating DMPM from other PSMs.
- To assess the prognostic value of these markers in DMPM patients.
- To identify potential biomarkers for improved DMPM diagnosis and patient management.
Main Methods:
- Serum samples from 30 DMPM patients and 14 controls with other PSMs were analyzed using enzyme-linked immunosorbent assay (ELISA) before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC).
- Receiver-operating characteristic (ROC) curves were generated to assess the diagnostic accuracy (AUC-ROC) of each marker.
- Multivariate analysis was performed to evaluate the prognostic significance of the markers.
Main Results:
- Significantly higher mean mesothelin (P=0.001) and CEA (P=0.008) levels were observed in the DMPM group compared to controls.
- Mesothelin (AUC-ROC=0.812) and CA19.9 (AUC-ROC=0.836) demonstrated good diagnostic performance.
- Elevated mesothelin (>5.21 ng/dl) showed 70% sensitivity and 100% specificity, while low CA19.9 (<8.8 U/dl) indicated 90% sensitivity and 85.7% specificity for DMPM.
- Osteopontin levels did not significantly differ between groups, but it correlated with survival (P=0.004) in DMPM patients.
Conclusions:
- Elevated serum mesothelin combined with low CA19.9 can increase suspicion for DMPM in cases of PSM with unknown origin.
- Osteopontin shows promise as a prognostic biomarker for DMPM and warrants further investigation.
- These findings may aid in the differential diagnosis and prognostication of DMPM.
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