Author of

• 18972

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  P2.02 - Biology/Pathology (ID 616)

  • Event: WCLC 2017
  • Type: Poster Session with Presenters Present
  • Track: Biology/Pathology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)

  • 23234

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    P2.02-036 - The Expression Pattern of CD26/DPP4 in Human Lung Cancer (ID 9319)

    09:30 - 09:30  |  Author(s): C. Alexandra
    • Abstract

    Background:
    Lung cancer is the leading cause of death among cancers. Despite improved surgical and novel radiation improvements, the overall prognosis remains poor. CD26/dipeptidyl peptidase 4 (DPP4) is a ubiquitously expressed transmembrane exopeptidase on the cell surfaces of many different cells including malignancies of breast, colon, and mesothelioma. Phase I data in mesothelioma with a specific antibody showed tolerability in mesothelioma patients.Our group found previously that the activity of CD26/DPP4 of lung adenocarcinoma (Adeno-CA) patients is four times higher than in normal 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 biomarker for lung cancer and a target for inhibition to reduce lung cancer burden. burden.
    
    Method:
    To identify CD26/DPP4 by immunohistochemistry (IHC), we tested four antibodies from Abcam, R/D systems, and Cell signaling technology on multi-organ tissue micro array (TMA) and human lung Adeno-CA cell lines (A549, H460, Gon8, Mai9) derived from advanced stage (IV) of human Adeno-CA. We selected the antibody from Cell signaling technology against CD26/DPP4. For the analysis of CD26/DPP4 by IHC in lung cancer samples, TMAs constructed from non-small cell lung cancer patients were used. The cohort consisted of 475 patients (Adeno-CA: 223; Squamous carcinoma: 252). The intensity of the staining was scored from 0 to 3 in a blinded manner. To quantify CD26/DPP4 in the supernatant of human lung Adeno-CA cell lines in vitro, ELISA was performed.
    
    Result:
    IHC scores revealed that Adeno-CA expresses significantly more CD26/DPP4 compared to squamous carcinoma (p<0.0001). Consistent with our previous findings, early stage cancer (IA) scores significantly higher than other stages IIB (p=0.0012), IIIA (p=0.0019), and IV (p=0.02) among Adeno-CA samples. We could not find CD26/DPP4 expression on human Adeno-CA cell lines by IHC, but the secretion of the protein in supernatant stays high (A549: 20pg/ml; H460: 161pg/ml; Gon8: 74pg/ml; Mai9: 648pg/ml).
    
    Conclusion:
    CD26/DPP4 expression was significantly higher at early stages of Adeno-CA samples when compared to advanced stages, supporting our previous findings. From the human cell line data, we suggest that advanced cancer secretes CD26/DPP4 more actively than early stage cancers. CD26/DPP4 seems to be a substantial target for inhibition of human Adeno-CA.