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Lele Zhang



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    P2.11 - Screening and Early Detection (ID 178)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Screening and Early Detection
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.11-18 - Circulating Serum KLK5 and L1CAM Levels Potentially Predict Clinical Outcome to Anlotinib Therapy in NSCLC Patients (ID 1074)

      10:15 - 18:15  |  Author(s): Lele Zhang

      • Abstract

      Background

      Anlotinib is an oral multi-targeted tyrosine kinase inhibitor (TKI), which has been demonstrated to be effective upon non-small cell lung cancer (NSCLC) in clinical trials at 3rd line. However, the underlying anlotinib-responsive patients remain elusive. In the present study, we aimed to screen out the potential biomarkers for anlotinib-responsive stratification via transcriptome analysis.

      Method

      Anlotinib-resistant NCI-H1975 cells were established in vitro. Toxicologic effects undergoing anlotinib stress were observed upon NCI-H1975 cells and anlotinib-resistant NCI-H1975 cells, respectively. Transcriptome profiling was performed to screen anlotinib resistance-associated genes between NCI-H1975 cells and anlotinib-resistant NCI-H1975 cells. The correlations between mRNA levels of the anlotinib resistance-associated genes and clinical outcomes of NSCLC patients were analyzed via Kaplan-Meier survival analysis in TCGA cohort. Potential biomarkers for anlotinib-responsive stratification were examined in a 28 patients’ cohort of anlotinib clinical trial (NCT02388919).

      Result

      Anlotinib-induced cytotoxic effects nearly disappeared in anlotinib-resistant NCI-H1975 cells, which are majority attributed to the modulated gene expression of multiple biological processes. Among these biological processes, angiogenesis plays an important role in anlotinib resistance. Up-regulation of angiogenesis-related KLK5 and L1CAM are mostly associated with poor clinical outcome in NSCLC patients. Knockdown of KLK5 and L1CAM contribute to increase anlotinib-induced cytotoxicity upon NCI-H1975 cells and anlotinib-resistant NCI-H1975 cells. High serum levels of KLK5 and L1CAM are also associated with poor anlotinib response in NSCLC patients at 3rd line.

      Conclusion

      This study suggested that serum levels of KLK5 and L1CAM potentially serve as biomarkers for anlotinib-responsive stratification in NSCLC patients at 3rd line.