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EP1.03 - Biology (ID 193)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 1
- Now Available
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
EP1.03-33 - CD26/DPP4 as a Novel Prognostic Marker for Lung Adenocarcinoma (Now Available) (ID 1734)
08:00 - 18:00 | Author(s): Wolfgang Jungraithmayr
CD26/dipeptidyl peptidase 4 (DPP4) is a transmembrane exopeptidase expressed on various malignancies in conjunction with activity of epithelial-mesenchymal transition (EMT). We found previously that the activity of CD26/DPP4 in human lung adenocarcinoma is four times higher than in normal lung tissue and the inhibition of CD26/DPP4 decreased the growth of lung tumors in experimental models. These data prompted us to analyze the expression of CD26/DPP4 and EMT markers in samples from non-small cell lung cancer patients to unravel a function of CD26/DPP4 as a prognostic marker and potential therapeutic target for lung cancer.Method
We employed multi-organ tissue micro array (TMA) of non-small cell lung cancer patient samples from two institutions, University Hospital Zurich and Dongsan Medical Center. To identify CD26/DPP4 and EMT markers (Ecadherin, Vimentin, beta-Catenin, Elastin, Periostin, and Versican), immunohistochemistry (IHC) on TMA was performed. Three pathologists scored the intensity IHC from zero to six in a blinded manner. The cohort consisted of 1126 patients (adenocarcinoma: 593; squamous carcinoma: 443; others (large cell carcinoma, adeno-squamous carcinoma): 90). The overall survival rate of patients was considered as a measure of prognosis. To identify a correlation between CD26/DPP4 and EMT related protein expression in lung cancer the Pearson correlation coefficient test was applied.
CD26/DPP4 IHC scores revealed that adenocarcinoma expresses significantly higher amount of the protein compared to normal lung or squamous carcinoma or others (p=0.035, p<0.0001, p<0.0001 respectively). In adenocarcinoma, patients with high CD26/DPP4 score (4-6) showed the worst overall survival compared to patients scoring low (1-3) or zero. The correlation analysis of CD26/DPP4 with EMT markers in adenocarcinoma showed that the epithelial marker Ecadherin was negatively correlated (p=0.001), while mesenchymal proteins Vimentin, beta-Catenin, Elastin were positively correlated with CD26/DPP4 (p=0.03, 0.01, and 0.001 respectively). Periostin and Versican showed no correlation with CD26/DPP4 expression.Conclusion
The expression of CD26/DPP4 was significantly higher in adenocarcinoma among non-small cell lung cancers and associated with worse survival of patients. Furthermore, the expression of CD26/DPP4 was significantly correlated with the EMT status. We therefore deem CD26/DPP4 to be a novel prognostic marker for lung adenocarcinoma. In consideration with CD26/DPP4 expression of these cancer samples, inhibition of CD26/DPP4 can potentially improve lung cancer patients’ survival.