CD157 plays a pivotal role in the progression of malignant pleural mesothelioma (MPM) and may be useful in the stratification of patients into different prognostic groups, Italian research suggests.
CD157 is known to contribute to tumour progression in ovarian cancer by promoting mesenchymal differentiation, and parallels between ovarian and mesothelial cancer indicate that CD157 might also be involved in MPM, explain Ada Funaro (University of Torino) and colleagues.
To investigate this hypothesis, Funaro and team conducted in vitro and in vivo assays using human MPM cell lines and MPM surgical tissue samples.
Using reverse transcriptase polymerase chain reaction and flow cytometry, they detected CD157 messenger RNA and protein expression in two of five epithelioid MPM cell lines and in one of three biphasic MPM cell lines.
Expression was also detected by immunohistochemistry in 85.2% of 81 MPM surgical tissue samples and was evenly distributed among epithelioid (86.5%) and biphasic (84.0%) tumours.
Statistical analysis revealed that CD157 expression did not correlate with gender, patient age at surgery, histology, asbestos history, disease stage or patient outcome when the 81 surgical MPM specimens were stratified by the median CD157 histology (H)-score of 50.
Similarly, when the data were analysed according to histotype, there was no correlation between survival and CD157 H-score in patients with epithelioid tumours.
However, the reverse was true for biphasic MPM, where a high CD157 H-score (>50) was significantly associated with worse survival compared with a low score, at a median of 13.1 versus 20.4 months and a hazard ratio of 2.43.
This finding prompted the researchers to further investigate the influence of CD157 on tumour cell behaviour in vitro.
They report that, in biphasic MPM cell lines, knockdown of CD157 in CD157-positive cells significantly reduced cellular growth, motility and invasiveness, whereas forced expression of CD157 in CD157-negative cells enhanced each of these variables. By contrast, no such effect was observed in the epithelioid cell lines.
Furthermore, increased CD157 expression in biphasic MPM cell lines correlated with increased resistance to platinum-based chemotherapy, via activation of the mTOR pathway, which is a known contributor to mesothelioma progression.
And patients with biphasic MPM and high CD157 expression receiving postoperative platinum-based chemotherapy showed a trend towards reduced survival compared with those with low CD157 expression who received the same type of treatment.
“These data suggest that CD157 could be a promising candidate as a predictive marker of response to platinum-based therapy in biphasic MPM patients”, Funaro and co-authors conclude in Oncotarget.
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