Biomarkers for malignant pleural mesothelioma: a meta-analysis

Abstract

Malignant pleural mesothelioma (MPM) is a rare but aggressive cancer, and early detection is associated with better survival. Mesothelin, fibulin-3 and osteopontin have been suggested as screening biomarkers. The study conducted a meta-analysis of the mean differences of mesothelin, osteopontin and fibulin-3 in blood and pleural samples. PubMed searches were conducted for studies that measured levels of mesothelin, osteopontin and fibulin-3 in participants with MPM compared with malignancy, benign lung disease or healthy participants. Thirty-two studies with mesothelin levels, 12 studies with osteopontin levels and 9 studies with fibulin-3 levels were included in the meta-analysis. Statistically significant mean differences were seen between MPM patients and all other comparison groups for mesothelin blood and pleural levels. Statistically significant differences in blood osteopontin levels were seen between participants with benign lung disease and healthy participants compared with participants with MPM, but not when comparing participants with cancer with MPM participants. There were not enough studies that reported osteopontin levels in pleural fluid to complete a meta-analysis. Statistically significant differences were seen in both blood and pleural levels of fibulin-3 in MPM patients compared with all other groups. On the basis of these results, mesothelin and fibulin-3 levels appear to be significantly lower in all control groups compared with those with MPM, making them good candidates for screening biomarkers. Osteopontin may be a useful biomarker for screening healthy individuals or those with benign lung disease but would not be useful for screening patients with malignancies.

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

“…All available meta-analyses confirmed that SMRP is elevated in the serum of MM patients as compared to healthy individuals, patients with asbestos-related diseases, benign respiratory diseases or lung cancer. 12,14,16 Previous studies suggest that serum SMRP levels are the highest in epithelioid MM, which is consistent with our results. 12,14 Our present study also included patients with peritoneal MM who were rarely represented in other studies or meta-analyses that focused on pleural MM.…”

“…Studies therefore suggest that SMRP measurement could be a potential screening tool for the detection of MM, but clinical use is still limited due to the probability of false positive and especially false negative results. 12,14,16 Some issues related to sensitivity may be associated with a difficult selection of an appropriate cutoff value and different studies found different optimal thresholds. 12,14,16 In our study, the standard cutoff of 1.5 nmol/l had 93% specificity and 59.3% sensitivity for distinguishing MM patients from other subjects.…”

“…The most frequently investigated biomarker in MM is mesothelin, as many studies have shown it is frequently increased in both tumor tissue and serum of MM patients, especially in epithelioid histological type. 8,[10][11][12][13][14][15][16][17] Mesothelin is a cell-surface glycoprotein expressed in mesothelial cells and overexpressed in several cancer types. It is involved in important cellular processes, including cell adhesion, proliferation, invasion, and epithelial-to-mesenchymal transition.…”

Asbestos-Related Diseases and Blood Biomarkers

“…Statistically, significant mean differences have been found between MM patients and all the other comparison groups for mesothelin blood and pleural levels. It has been concluded that based on the findings, mesothelin levels seem to be significantly lower in all control groups compared with those with MM, suggesting a possible role of mesothelin as a screening biomarker for MM [30].…”

“…The meta-analysis of Gillezeau et al, which includes nine studies with fibulin-3 levels, also presented a statistically significant difference in both blood and pleural levels of fibulin-3 in MM patients compared with those of all other groups [30].…”