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Wolfgang Jungraithmayr
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P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.01-51 - Study of CD26/DPP4 Expression in a Large Series of Non-Small Cell Lung Cancer Patients (ID 13794)
16:45 - 18:00 | Author(s): Wolfgang Jungraithmayr
- Abstract
Background
Lung cancer is a leading cause of cancer-related death worldwide and the prognosis remains poor CD26/dipeptidyl peptidase 4 (DPP4) is a transmembrane exopeptidase expressed on various hematopoietic but also somatic cells including malignancies of breast, colon, and mesothelioma. We previously found 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 in samples from lung cancer patients to unravel the role of CD26/DPP4 as a potential therapeutic target to reduce lung cancer burden.
a9ded1e5ce5d75814730bb4caaf49419 Method
To identify CD26/DPP4, we performed immunohistochemistry (IHC) on multi-organ tissue micro array (TMA) using four different antibodies. We finally selected the antibody produced by Cell Signaling Technology. For the analysis of CD26/DPP4 by IHC, TMAs constructed from the samples of non-small cell lung cancer patients were used. The cohort consisted of 1110 patients (Adenocarcinoma (AC): 567; Squamous carcinoma (SC): 443). Three pathologists independently scored the staining intensity from zero to three in a blinded manner. Lung AC cell lines from tissue (H2347, H522, A549, and Hop62) and pleural malignant effusion (H1437, H460, Mai9, and Gon8) were employed to assess the expression of CD26/DPP4. ELISA was used to quantify CD26/DPP4 from cell lines.
4c3880bb027f159e801041b1021e88e8 Result
Overall survival of the patients showed no difference between AC and SC groups. IHC scores revealed AC expressing significantly higher CD26/DPP4 levels vs. normal lung or SC (p=0.035, p<0.0001, respectively). In consistency with our previous findings, early stage cancer (IA) expresses significantly higher levels of CD26 than other stages IIB (p=0.0012), IIIA (p=0.0019), and IV (p=0.02) among AC samples. From our in vitro studies, we found that early stage derived cell line (H2347: stage I) expresses significantly more CD26/DPP4 compared to others (H522: stage II, A549 and HOP62 stage IV). In contrast, metastatic AC cell lines secrete significantly more CD26/DPP4 in culture medium compared to tissue derived cell lines, while the cellular level of CD26/DPP4 was higher in tissue derived cell lines.
8eea62084ca7e541d918e823422bd82e Conclusion
AC expresses significantly more CD26/DPP4 than SC. Furthermore, the expression of CD26/DPP4 was higher at early stages of AC compared to advanced stages. Human cell line data suggest that metastatic AC secretes CD26/DPP4 more actively than primary cancer. We therefore deem CD26/DPP4 to be a target for inhibition of human AC.
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