Author of

• 18974

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  P3.02 - Biology/Pathology (ID 620)

  • Event: WCLC 2017
  • Type: Poster Session with Presenters Present
  • Track: Biology/Pathology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)

  • 23971

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    P3.02-023 - Semaphorin 7A Reduces Response to EGFR-TKI Treatment via Apoptosis in Human Lung Adenocarcinoma (ID 8074)

    09:30 - 09:30  |  Presenting Author(s): Yuhei Kinehara
    • Abstract

    Background:
    Most patients harboring epidermal growth factor receptor (EGFR) mutations experience relapse to EGFR-Tyrosin kinase inhibitors (TKI). So it is necessary to overcome the resistance to EGFR-TKI. We found that Semaphorin 7A (SEMA7A) is upregulated by EGFR signals. The role of SEMA7A in human lung adenocarcinoma is unknown, so we annlyzed the function of SEMA7A in human lung adenocarinoma.
    
    Method:
    We compared transcriptomes of NIH3T3 cell lines overexpressing wild type (WT) EGFR with Next, we investigated which pathways regulated the expression of SEMA7A in human lung adenocarcinoma cell line. Furthermore, we investigated the expression of SEMA7A by immunohistochemistry (IHC), and the correlation of SEMA7A and phosphorylation S6 (pS6) in 129 lung adenocarcinoma patients were analyzed. We also investigated the correlation of SEMA7A expression with the prognosis or drug response in 44 stage IV lung adenocarcinoma patients. Finally, we investigated the efficacy of EGFR-TKI in SEMA7A WT and KO (by CRISPR/CAS9) in vitro and in vivo.
    
    Result:
    The expression of SEMA7A was regulated by EGFR signals. Furthermore, the expression of SEMA7A was downregulated by mTOR signals in human lung adenocarinoma cells and clinical samples. High SEMA7A lung cancers tended to get EGFR-TKI resistance, in vivo, in vitro via apoptosis. In clinical samples, high SEMA7A expression tumor tended to get EGFR-TKI resistance.
    
    Conclusion:
    We revealed that the SEMA7A regulated the efficacy to EGFR-TKI via apoptosis.