Longitudinal monitoring of response to chemotherapy in patients with malignant pleural mesothelioma by biomarkers.

BACKGROUND: The aim of the study was to longitudinally investigate the serum levels of mesothelin, sestrin1, hyaluronan synthase 2 (HAS2), midkine, and high mobility group box 1 (HMGB1) before and after chemotherapy and at the time of relapse in malignant pleural mesothelioma (MPM) patients treated with chemotherapy and to compare the changes in biomarker levels with radiological treatment outcome. METHODS: A total of 64 MPM patients treated with chemotherapy were enrolled in the study and longitudinally followed for changes in biomarker levels in response to treatment. Biomarkers levels were measured in serum using a human ELISA kit. Relative and absolute changes in biomarker levels were compared with the best radiological overall response at each time point. RESULTS: Median survival was 20.0 ± 2.4 (15.3-24.7) months in patients with partial and complete response, 17.0 ± 1.0 (15.0-19.0) months in patients with stable disease, and 9.0 ± 1.0 (7.0-11.0) months in patients with progressive disease. A significant decrease in serum levels of mesothelin, midkine, and HMGB1 was observed in patients with radiologically partial and complete responses to chemotherapy (p< 0.001, p= 0.016, and p= 0.039, respectively). In these patients, mesothelin levels decreased by 15%, midkine levels by 7%, and HMGB1 levels by 15%. In addition, HMGB1 serum levels were found to significantly increase by 15% in patients with radiologically progressive responses to chemotherapy compared to pretreatment serum levels (p= 0.035). In patients with partial and complete response to chemotherapy, mesothelin levels increased by 15%, midkine by 12%, and sestrin1 by 8% when the disease recurred (p= 0.004, p= 0.004 and p= 0.044, respectively). CONCLUSION: Biomarkers may be useful in the longitudinal monitoring of response to treatment in MPM. However, the results of our study should be validated in larger groups with sufficient case numbers from multicenter institutions.

Serum Expression Levels of Certain miRNAs in Predicting Diagnosis, Prognosis, and Response to Chemotherapy in Malignant Pleural Mesothelioma

Background: miRNAs are involved in tumor pathogenesis and can therefore be determined in the primary tumor, plasma and serum, and body fluids. As in various cancers, their role in the diagnosis, prognosis, and treatment of patients with malignant pleural mesothelioma (MPM) may be important. Aims: To analyze the predictive value of miR-16-5p, miR-29c-3p, miR-31-5p, miR-125a-5p, miR-320a, miR-484 and miR-532-5p expressions for diagnosis, prognosis and response to treatment in patients with MPM. Study Design: Prospective case-control study. Methods: In the first phase of the study, blood samples were collected from 101 MPM patients before chemotherapy and from 24 healthy donors (HDs). In the second phase, the blood samples were collected from 74 MPM patients who had received chemotherapy when the best overall response and disease recurrence were determined. A quantitative real-time polymerase chain reaction was undertaken to detect the miRNA expression levels. The miRNA expression profiles of MPM patients were compared with those of HDs. The associations between the expression levels of miRNAs and prognosis and response to treatment were then evaluated. Results: All miRNAs, except miR-31-5p, were expressed differently in MPM relative to that in HDs. The expression level of miR-16-5p decreased when compared with that of HDs, and the expression levels of miR-29c-3p, miR-125a-5p, miR-320a, miR-484, and miR-532-5p increased when compared with that of HDs. The sensitivity and specificity values of miR-29c-3p, miR-125a-5p, miR-320a, miR-484, and miR-532-5p for discriminating MPM from HDs were 85.9% and 59.1%, 95.1% and 62.5%, 87.1% and 79.2%, 82.2% and 58.3%, and 69.3% and 82.6%, respectively. After adjusting for the histological subtype, stage, and treatment, the miR-29c-3p, miR-125a-5p, and miR-484 were associated with longer survival. The miRNA expression levels did not change longitudinally for the determination of chemotherapy response and recurrence. Conclusion: miRNAs may be useful in diagnosing patients with MPM and provides helpful information in determining the prognosis of patients.

Asbestos knowledge and awareness level in central part of Anatolia.

Background Asbestos-contaminated soil has been used by people for many years in the rural part of Anatolia. However, there is no program to control usage of asbestos in this region. Objective To determine the knowledge and awareness level about asbestos in a region where asbestos-related diseases are endemic due to environmental exposure to asbestos in the rural setting. Methods This study included 760 participants, recruited using non-probability sampling, who were classified into four groups according to residence and asbestos exposure type (urban, rural; asbestos-exposed, asbestos-unexposed). Asbestos knowledge and awareness was measured via the Asbestos Knowledge and Awareness Questionnaire (AKAQ). The cut-off value of questionnaire was determined by the K-means cluster analysis for sufficient and insufficient knowledge and awareness level. A multiple logistic regression analysis was performed to determine independent factors affecting sufficient knowledge and awareness of participants about asbestos. Results The median and mean score of the AKAQ in study group were 30 and 33.9, respectively. The urban asbestos-exposed group had a higher score than the urban asbestos-unexposed and both rural groups (p < 0.001). Factors affecting asbestos knowledge and awareness were education status (p = 0.035), asbestos exposure (p = 0.003) and living in the rural area (p = 0.005). Sufficient knowledge and awareness (score > 45) was higher among participants who had graduated from university and had asbestos exposure. Insufficient knowledge and awareness level was higher among participants living in rural areas. Conclusion In this region of Anatolia, knowledge and awareness level of asbestos was low among people at risk for environmental asbestos exposure. People should be aware of asbestos and its hazards by a well-designed training program and be monitored for asbestos-related diseases.