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Vilde D Haakensen

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    P1.02 - Biology/Pathology (ID 614)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P1.02-028 - Pathways Involved in Early Stage Lung Cancers (ID 9087)

      09:30 - 16:00  |  Presenting Author(s): Vilde D Haakensen

      • Abstract
      • Slides

      Lung cancer is a heterogeneous disease and we have few good markers of therapy prediction for chemotherapy and even immunotherapy. The biological mechanisms driving the tumour growth of different tumours even within the same histology are likely to vary and cause the diversity in therapy response. Pathifier is an algorithm developed by Eaton Domany’s group (Drier Y et al. PNAS, 2013 ) to estimate the deregulation of pathways of tumour samples based on mRNA expression levels of the genes in the pathway. Briefly, the algorithm estimates the deviation of the pathway in the tumour samples compared with normal samples. We analyse pathways deregulated in early stage squamous cell carcinomas to identify pathways potentially linked to therapy response. Such analyses have been performed for breast cancer (Livshits A et al, MolOnc, 2015), but have so far not been applied to lung carcinomas.

      A total of 198 patients undergoing surgery for squamous cell lung cancer were included in the study. mRNA was extracted from the surgically resected tumour from all patients and from adjacent normal lung tissue from 22 patients. An adjustment of the pathifier algorithm was developed to avoid over-estimation of pathway deregulation. The samples were clustered according to adjusted pathway deregulation. Extensive clinical information such as mutation status, smoking history and survival was available.

      Hierarchial clustering of the adjusted pathway deregulation scores identified separate clusters of squamous cell carcinomas of the lung dominated by different biological pathway with putative difference in clinical behaviour. Based on the biological activity, subgroups of patients are suggested to respond to immunotherapy and cell cycle inhibitors. The clusters are linked with survival, smoking history and expression of immune-related genes including PD-L1.

      Subgroups of lung squamous cell carcinomas have different biology represented by deregulation of groups of pathways. These biological differences can be used to identify clinically relevant markers of prognosis and therapy prediction. The results should be validated in functional studies.

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