Soluble CD157 in pleural effusions: a complementary tool for the diagnosis of malignant mesothelioma

Abstract

BackgroundCD157/Bst1 glycoprotein is expressed in >85% of malignant pleural mesotheliomas and is a marker of enhanced tumor aggressiveness.ResultsIn vitro, mesothelial cells (malignant and non-malignant) released CD157 in soluble form or as an exosomal protein. In vivo, sCD157 is released and can be measured in pleural effusions by ELISA. Significantly higher levels of effusion sCD157 were detected in patients with malignant pleural mesothelioma than in patients with non-mesothelioma tumors or with non-malignant conditions. In our patient cohort, the area under the receiver-operating characteristic curve for sCD157 that discriminated malignant pleural mesothelioma from all other causes of pleural effusion was 0.685, cut-off (determined by the Youden Index) = 23.66 ng/ml (62.3% sensitivity; 73.93% specificity). Using a cut-off that yielded 95.58% specificity, measurement of sCD157 in cytology-negative effusions increased sensitivity of malignant pleural mesothelioma diagnosis from 34.42% to 49.18%.ConclusionsEvaluation of soluble CD157 in pleural effusions provides a diagnostic aid in malignant mesothelioma.MethodsSoluble CD157 (sCD157) was detected biochemically in culture supernatants of malignant and non-malignant mesothelial cells, and in pleural effusions from various pathological conditions. An ELISA system was established to measure the concentration of sCD157 in fluids, and extended to analyze sCD157 in pleural effusions from a cohort of 295 patients.

CD157: From immunoregulatory protein to potential therapeutic target

“…Recent results from our group demonstrated that soluble CD157 levels is significantly higher in MPM effusions than in all other pleural effusions, both non-MPM malignant and non-malignant. Although sCD157 does not have the required accuracy for diagnostic purposes by its own, measurement of effusion sCD157 can provide supporting evidence for diagnosing MPM in symptomatic individuals when cytology is inconclusive [15].…”

“…CD157 protein has a molecular weight ranging between 42-50 kDa due to its heterogeneous glycosylation patterns [13]. CD157 exists both as membrane-bound and as a soluble protein that is measurable in sera [14] and in pleural and peritoneal effusions [15].…”

CD157: From Myeloid Cell Differentiation Marker to Therapeutic Target in Acute Myeloid Leukemia

“…Very high levels of soluble CD157 were reported in the sera of patients with rheumatoid arthritis compared to healthy controls [21]. Elevated soluble CD157 was also found in pleural effusions from patients with malignant pleural mesothelioma compared to patients with other cancer types or benign pathologies [22]. Recently, the concentration of soluble CD157 was found to be significantly increased in pleural fluid obtained from tuberculous pleurisy patients with respect to patients with pneumonia or lung cancer [23].…”

“…CD157 can be shed either as a soluble protein, generated by proteolytic cleavage of the membrane-bound form, or as an exosome-anchored protein. CD157 was found to be expressed by exosomes released by myeloid-derived suppressor cells [24] and by mesothelioma cells, both in vitro [25] and in vivo [22]. The functional role of soluble CD157 remains to be defined.…”

CD157 Confers Host Resistance to Mycobacterium tuberculosis via TLR2-CD157-PKCzeta-Induced Reactive Oxygen Species Production

“…In addition, CD157 expressed by epithelial ovarian cancer cells and pleural mesothelioma cells controls tumor cell migration and invasion (14, 15). In addition to existing as a glycosylphosphatidylinositol (GPI)-anchored membrane protein implicated in the control of leukocyte trafficking, CD157 also presents as a soluble protein whose biological role is unknown (16, 17).…”