Abstract
Purpose
Anlotinib is an oral small-molecule multitarget tyrosine kinase inhibitor that hampers neovascularization thus providing antitumor effect. The ALTER 0303 trial was a multicenter, double-blind, phase 3 randomized clinical study to evaluate the efficacy of anlotinib in patients with advanced non-small cell lung cancer (NSCLC). The ALTER 0303 results showed that patients in the anlotinib group had a median progression-free survival of 5.4 months, a significant improvement compared with 1.4 months in the placebo group; however, median overall survival was only extended by 3.3 months (9.6 vs 6.3 months). The problem of anlotinib resistance cannot be ignored, and an in-depth exploration of biomarkers of anlotinib treatment response is urgently needed to further improve the efficacy of anlotinib in the treatment of NSCLC. This study aimed to identify plasma exosome markers that could be used to monitor the efficacy of anlotinib.
Methods
We enrolled 5 patients with advanced NSCLC, and 15 blood samples were collected before anlotinib treatment, when the treatment was effective, and when the treatment was ineffective. The plasma exosomal RNA profiles were analyzed by whole-transcriptome sequencing at three different stages. The expression of dysregulated exosomal RNAs in 43 additional patients was also verified by real-time quantitative PCR.
Results
In the plasma exosomal RNA profiles of the 5 patients with advanced NSCLC during treatment with anlotinib, 7 miRNAs, 3 lncRNAs, and 83 mRNAs were significantly dysregulated. The regulation trend was opposite when the treatment was effective and ineffective, showing dynamic changes. After validation, we finally found that plasma exosomal lnc-SNAPC5-3:4 was significantly upregulated when anlotinib treatment was effective, and it was significantly downregulated when the treatment failed (p < 0.05). Thus, it can be used as a potential biomarker for monitoring the efficacy of anlotinib.
Conclusion
Our results demonstrate the potential of plasma exosomal lnc-SNAPC5-3:4 as a biomarker for monitoring anlotinib efficacy.
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Data availability
Data are available from the corresponding author on reasonable request.
Code availability
Not applicable.
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Funding
This work was supported by the Natural Science Foundation of China (8170130783), Natural Science Foundation of Jiangsu Province, China (No. BK20191211), The “521” talent project of Lianyungang city (LYG06521202158), The technology project of the High-tech Zone of Lianyungang city (ZD201930).
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All the authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Chun Liu. The first draft of the manuscript was written by Chun Liu and Chenxi Hu. All the authors commented on previous versions of the manuscript. All the authors read and approved the final manuscript.
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This study was approved by the Ethics Committee of the Affiliated Lianyungang Hospital of Xuzhou Medical University (IRB no. KY-20210429002–01). All the patients signed a written informed consent.
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Liu, C., Hu, C., Chen, T. et al. The role of plasma exosomal lnc-SNAPC5-3:4 in monitoring the efficacy of anlotinib in the treatment of advanced non-small cell lung cancer. J Cancer Res Clin Oncol 148, 2867–2879 (2022). https://doi.org/10.1007/s00432-022-04071-5
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DOI: https://doi.org/10.1007/s00432-022-04071-5