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Lars Jørgensen

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    MA21 - Molecular Subtyping, CBL3, and Non Coding RNA (ID 924)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Biology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 15:15 - 16:45, Room 205 BD
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      MA21.06 - Proteins Associated with Survival Differ Depending on Molecular Subtypes, and Mutational- and Smoking-Status In NSCLC Biopsies (ID 13769)

      15:50 - 15:55  |  Author(s): Lars Jørgensen

      • Abstract
      • Presentation
      • Slides


      Purpose: Proteins are the functional players driving both normal and disease physiology. The proteomic changes observed in lung cancer may be a consequence of mutations in essential driver-genes. The purpose of this study was to identify proteins in lung cancer biopsies associated with survival in groups stratified by smoking status, and EGFR-, TP53- and KRAS-mutations.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We have performed a profiling of 295 cancer relevant proteins, of which 60 were in a phosphorylated state, using reverse phase protein arrays (RPPA). We analyzed biopsies from 80 lung cancer patients (adenocarcinoma) and correlated the protein expression pattern with progression free survival (PFS) based on mutational- and smoking-status.

      4c3880bb027f159e801041b1021e88e8 Result

      Spearman correlation analysis revealed a higher number of proteins with significant association to PFS (p<0.05) among the wild type samples compared to the mutated samples. High expression of protein kinase C (PKC) and the isoforms alpha, beta and delta, included the phosporylated state, showed the strongest association with better PFS, especially in the wild type samples. Ten proteins were associated with PFS in never-smokers, where eight of these were unique for this group.

      Unsupervised hierarchical clustering separated the samples into four subclusters, each enriched with one of the three molecular subtypes TRU, PI and PP (Comprehensive molecular profiling of lung adenocarcinoma, Nature, 2014). Subcluster 2 contained two smaller clusters (2a and 2b) enriched with samples of subtype PP, where subcluster 2a was associated with poor PFS (p=0.003, Figure 1).


      8eea62084ca7e541d918e823422bd82e Conclusion

      As of today, we do not have any effective treatment targeting KRAS- and TP53- mutated cells. This study shows that expression of specific proteins and phospho-proteins associated with PFS differ depending on molecular subtype, and mutational- and smoking-status. Proteins associated with PFS may serve as therapeutic targets to circumvent treatment resistance.


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