Author of

• 30723

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  P1.03 - Biology (ID 161)

  • Event: WCLC 2019
  • Type: Poster Viewing in the Exhibit Hall
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall

  • 30777

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    P1.03-48 - Vasohibin 2 Promotes Angiogenesis and Lymphangiogenesis of Lung Squamous Cell Carcinoma Through Snail-Dependent VEGF-D Signaling Pathway (ID 770)

    09:45 - 18:00  |  Presenting Author(s): Pengpeng Liu
    • Abstract

    Background
    

    Tumor metastasis is a process in which tumor cells spread to the secondary sites via the lymphatic and blood vessels. In lung squamous cell carcinoma (LUSC), the molecular mechanisms involved in lymphangiogenesis and lymphatic metastasis remain unclear.

    Method
    

    We analyzed mRNA expression profiles of 535 primary LUSC samples from TCGA to screen the most differentially expressed genes related to the poor prognosis of LUSC patients and validated in an independent Chinese LUSC cohort. We focused on Vasohibin 2 (VASH2) and investigated its biological functions in LUSC proliferation, apoptosis, migration, invasion, as well as lymphangiogenesis by forced over-expressing VASH2 in LUSC cell line H520 in vitro. We also investigated the anti-tumor efficacy of VASH2 target treatment in LUSC xenograft-bearing mice models.

    Result
    

    We identified 12 genes closely related to poor prognosis of LUSC patients, among which VASH2 was validated in an independent Chinese LUSC cohort and displayed high potential of lymphatic metastasis. Forced over-expression of VASH2 promoted the proliferation and invasion of LUSC cells via up-regulating specific transfer factor snail. Furthermore, VASH2 facilitated lymphangiogenesis and angiogenesis via up-regulation of snail-dependent vascular endothelial growth factor-D (VEGF-D) in LUSC cells in vitro and vivo. Importantly, specific VASH2 blocking antibody dramatically inhibited tumor development and progression in LUSC xenograft-bearing mouse models by interfering tumor proliferation and lymphangiogenesis in situ.

    Conclusion
    

    In conclusion, VASH2 might serve as a novel predictive biomarker and a potential therapeutic target for LUSC via inhibiting tumor growth and local lymphangiogenesis.

• 30943

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  P2.04 - Immuno-oncology (ID 167)

  • Event: WCLC 2019
  • Type: Poster Viewing in the Exhibit Hall
  • Track: Immuno-oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall

  • 30993

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    P2.04-43 - High Occurrence of LINE-1 Retrotransposition Is Correlated with Smoking History, Local Immunosuppression and Poor Prognosis in LUSC (ID 773)

    10:15 - 18:15  |  Author(s): Pengpeng Liu
    • Abstract

    Background
    

    Somatic Long Interspersed element-1 (LINE-1) retrotransposition (RT) is a genomic process that relates to gene disruption and tumor occurrence. However, the expression and function of LINE-1 RT in lung squamous cell carcinoma (LUSC) remains unclear.

    Method
    

    We analyzed the transcriptomes of paired LUSC samples in The Cancer Genome Atlas (TCGA), to characterize the most common somatic LINE-1 RTs in LUSC, followed by validation in an independent Chinese LUSC cohort and several cancer cell lines. We also analyzed the association between these LINE-1 RTs and clinico-pathology features, as well as the immunocyte content in local LUSC tumor tissues.

    Result
    

    We observed LINE-1 RT occurred within 90% of tumor samples in TCGA, among which thirteen LINE-1 RTs were filtered for high occurrence in LUSC. In Chinese cohort, the expression of 13 LINE-1 RTs in LUSC tissues was significantly higher than those in matched adjacent normal tissues. Furthermore, 11 of 13 LINE-1 RTs were exclusively detected in LUSC cell lines rather than normal lung epithelial cells. Further analysis showed 3 LINE-1 RTs, including L1-FGGY, L1-ATP8B1 and L1-SVEP1 were correlated with smoking history, large tumor size, central tumor location, and poorer prognosis. The immunohistochemical staining (IHC) analysis showed that less CD3⁺ T cells, more CD68⁺ macrophages and CD33⁺ myeloid-derived suppressive cells (MDSCs) were detected in LINE-1 RT positive tissues which implied that LINE-1 RT might induce significant immunosuppression in situ.

    Conclusion
    

    In conclusion, LINE-1 RT is a frequent genomic event that correlates with smoking-related LUSC development and LUSC immune evasion which might be a promising predictive biomarker of poor prognosis in LUSC.