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  P3.12 - Small Cell Lung Cancer/NET (Not CME Accredited Session) (ID 978)

  • Event: WCLC 2018
  • Type: Poster Viewing in the Exhibit Hall
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall

  • 27649

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    P3.12-10 - Immunogenomic Characteristics of SCLC and LCNEC Redefined Molecular Subgroups (ID 12577)

    12:00 - 13:30  |  Author(s): Jun Hou
    • Abstract
    • Slides

    Background
    

    While small-cell lung cancer (SCLC) and large-cell neuroendocrine carcinoma (LCNEC) are distinct classes of high-grade neuroendocrine carcinomas, the differential diagnosis between SCLC and LCNEC remains challenging. In fact SCLC and LCNEC overlap in clinical, histopathologic, cytologic, morphologic and genetic characteristics. Molecular profiling with microarray or next-generation sequencing has provided growing evidence suggesting that both SCLC and LCNEC are biologically heterogeneous and a great part of them are borderline neuroendocrine carcinomas falling between typical SCLC and LCNEC. On account of accumulated knowledge, we speculated that immunogenomically characterizing SCLC and LCNEC collectively as one group, or rather morphologically or cytologically separating SCLC from LCNEC has superior clinical value.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    We analyzed gene expression profiles of 44 SCLCs, 56 LCNECs and 25 normal lung samples obtained from Gene Expression Omnibus. Unsupervised and supervised analyses were performed to understand molecular characteristics of samples. Pathway and CIBERSORT analyses were employed to obtain immune landscape of SCLC and LCNEC.

    4c3880bb027f159e801041b1021e88e8 Result
    

    Unsupervised clustering with 1189 differentially expressed genes revealed 2 distinct molecular subgroups (G1 and G2) of SCLC and LCNEC, which is not associated with histopathology. Targeted pathway analysis found that G1 was marked by activated IL-17, MAPK and Hippo signaling pathways. In contrast, transcriptional factors, such as ASCL1, INSM1, SOX2, and NKX2-1 were significantly up-regulated in G2, but not in G1. Moreover, in silico analysis of cellular composition and expression of immune genes disclosed unique immunoprofiles for G1 and G2. G1 was characterized by enriched CD4 memory cells, M1 macrophages and activated dendritic cells. While G2 was composed of high fractions of memory B cells and naïve CD4 cells. Strikingly, expression of both immunoinhibitors (IL10, PDL1, IDO1) and immunomodulators (OX40L, BAFF, GITR, IL6), as well as MHC class I and II molecules was higher in G1 compared to that in G2.

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    We identified the common intrinsic features and molecular subgroups of SCLC and LCNEC, which are beyond conventional histopathology and better associated with immunogenomics of tumors. Further research is warranted to identify potential clinical implication of SCLC and LCNEC molecular subgroups.

    6f8b794f3246b0c1e1780bb4d4d5dc53

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