An analysis of succinate dehydrogenase B in pleural mesothelioma

To investigate the expression of succinate dehydrogenase B and its potential as a therapeutic target in pleural mesothelioma (PM).

The expression of succinate dehydrogenase B was examined in cell lines using PCR. The expression of succinate dehydrogenase B mRNA was subsequently examined in a series of fresh-frozen primary patient samples using reverse transcription polymerase chain reaction. The expression of succinate dehydrogenase B protein was examined by immunohistochemistry on a pleural mesothelioma tissue microarray derived from Formalin-Fixed and Paraffin-Embedded specimens to determine if succinate dehydrogenase B expression correlated with survival benefit. Using a resazurin-based assay we examined whether targeting the mitochondrial complex II (containing succinate dehydrogenase B) with a chemical inhibitor could have effects on cell proliferation.

Total ribonucleic acid was isolated from a panel of mesothelial-derived cell lines (both cancerous and non-cancerous), and expression of succinate dehydrogenase B messenger RNA was assessed by RT-PCR and found to be ubiquitously expressed. Total Ribonucleic acid was isolated from a panel of fresh-frozen surgical specimens, and succinate dehydrogenase B was significantly overexpressed in mesothelioma at the messenger RNA level. Immunohistochemical staining and analysis of a mesothelioma tissue microarray showed that expression did not correlate with any survival benefit, confirmed by in silico analyses of other datasets. However, links between DNA methylation at individual residues of the succinate dehydrogenase B gene and overall survival were identified, along with correlations to immune cell infiltrates. Targeting the mitochondrial complex II with oxaloacetic acid did not show any significant potential for higher efficacy in cell lines derived from malignant tumors compared to those derived from normal mesothelial cells.

Our results demonstrate that succinate dehydrogenase B is overexpressed in PM but may not be a suitable candidate for therapeutic targeting in this disease.