PROLINE DEHYDROGENASE EXPRESSION, REGULATION AND FUNCTION IN NON-SMALL CELL LUNG CARCINOMA

Non-Small Cell Lung Cancer (NSCLC) is one of the most frequent and deadliest cancers and comprises two main histotypes, adenocarcinoma (ADC) and squamocellular carcinoma (SCC). Identification of markers to better define the diagnosis, prognosis and therapeutic options of NSCLC is needed. We investigated if proline dehydrogenase (PRODH), a mitochondrial flavoenzyme catalyzing the key step in proline degradation, and involved in the regulation of cell survival, autophagy and apoptosis, may be one such marker. Materials and methods We characterized PRODH expression in NSCLC by immunohistochemistry and qPCR and tested if there was correlation between expression of PRODH and clinical features of the tumors or expression of other markers. We aimed to test what cellular processes are influenced by PRODH in lung ADC cell lines. To do so, we tested the effect of regulating PRODH expression in ADC tumour cell lines on their behaviour, by performing a panel of phenotypic assays. Results and discussion We found PRODH immunostaining in the majority (70%) of lung ADCs. Patients with PRODH positive tumors had better overall survival than those with negative tumors. Protein staining was paralleled by high transcript levels, suggesting transcriptional regulation. In A549 and H1437 ADC cell lines, ectopic modulation of PRODH expression suggested that PRODH favoured survival of these ADC cells, whereas in NCI-H1650 cells overexpression led to a decrease in clonogenic ability. In the latter cell line, PRODH expressing clones also showed a reduced 3D growth in soft agar compared to control clones. Conclusion Our immunohistochemistry data support a possible use of PRODH immunostaining as a prognostic marker. However, further research is necessary to 1) identify molecular interactors that can influence the outcome and 2) to better define the downstream processes activated by PRODH in lung cancer cells