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Åslaug Helland



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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): Åslaug Helland

      • Abstract
      • Presentation
      • Slides

      Background

      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).

      heatmap_subtypes_mod.png

      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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    P3.03 - Biology (Not CME Accredited Session) (ID 969)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.03-26 - Tumor Immune Microenvironment in NSCLC is Predictive of Prognosis After Surgery (ID 13802)

      12:00 - 13:30  |  Author(s): Åslaug Helland

      • Abstract

      Background

      To investigate the tumor microenvironment in NSCLC and try to understand more about how, and why, it differs in histological and expression subtypes of NSCLC .

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Samples were collected from 399 patients who underwent surgery for stage I-IV NSCLC at Oslo university hospital 2006-16. Gene expression was assessed by using Agilent microarray on samples from adenocarcinomas (n=184) and squamous cell carcinomas (n=183) separately. RNA sequencing was performed of 32 samples. Of these 53 % (n=17) were adenocarcinomas (AD) and 47 % (n=15) were squamous cell carcinomas (SCC). Xcell(1) was used to find the proportion of different cells in the tumor microenvironment and to calculate an immunescore. All samples were assigned a gene expression subtype by using previously described nearest centroid classifiers for AD and SCC respectively (2, 3)

      4c3880bb027f159e801041b1021e88e8 Result

      For AD we found significant differences in progression free survival (PFS) between the three expression subtypes with better prognosis for TRU versus non-TRU and worse for PP versus non-PP, adjusted for stage. We found no differences in prognosis between SCC expression subtypes. Higher immune score was associated with better PFS in AD but not in SCC.

      8eea62084ca7e541d918e823422bd82e Conclusion

      The composition of both stromal and immune cells in the tumor microenvironment will be further investigated. Differential gene expression analysis will be preformed to better understand what differentiates immunologically active from immunologically silent tumors.

      1. Aran D, Hu Z, Butte AJ. xCell: digitally portraying the tissue cellular heterogeneity landscape. Genome Biol. 2017;18(1):220.

      2. Wilkerson MD, Yin X, Walter V, Zhao N, Cabanski CR, Hayward MC, et al. Differential pathogenesis of lung adenocarcinoma subtypes involving sequence mutations, copy number, chromosomal instability, and methylation. PLoS One. 2012;7(5):e36530.

      3. Wilkerson MD, Yin X, Hoadley KA, Liu Y, Hayward MC, Cabanski CR, et al. Lung squamous cell carcinoma mRNA expression subtypes are reproducible, clinically important, and correspond to normal cell types. Clin Cancer Res. 2010;16(19):4864-75.

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