Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, 222000, Jiangsu, People's Republic of China.
Lianyungang Clinical College of Nanjing Medical University, Lianyungang, 222000, Jiangsu, People's Republic of China.
J Cancer Res Clin Oncol. 2022 Oct;148(10):2867-2879. doi: 10.1007/s00432-022-04071-5. Epub 2022 Jun 7.
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.
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.
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.
Our results demonstrate the potential of plasma exosomal lnc-SNAPC5-3:4 as a biomarker for monitoring anlotinib efficacy.
安罗替尼是一种口服小分子多靶点酪氨酸激酶抑制剂，可抑制新生血管生成，从而发挥抗肿瘤作用。ALTER 0303 试验是一项多中心、双盲、III 期随机临床试验，旨在评估安罗替尼治疗晚期非小细胞肺癌（NSCLC）患者的疗效。ALTER 0303 结果显示，安罗替尼组患者的中位无进展生存期为 5.4 个月，与安慰剂组的 1.4 个月相比有显著改善；然而，中位总生存期仅延长了 3.3 个月（9.6 个月 vs 6.3 个月）。安罗替尼耐药的问题不容忽视，深入探讨安罗替尼治疗反应的生物标志物，对于进一步提高安罗替尼治疗 NSCLC 的疗效具有重要意义。本研究旨在鉴定可用于监测安罗替尼疗效的血浆外泌体标志物。
我们纳入了 5 例晚期 NSCLC 患者，在安罗替尼治疗前、治疗有效时和治疗无效时采集了 15 份血样。采用全转录组测序技术分析了这三个不同阶段的血浆外泌体 RNA 谱。通过实时定量 PCR 验证了另外 43 例患者中失调的外泌体 RNA 的表达情况。
在 5 例接受安罗替尼治疗的晚期 NSCLC 患者的血浆外泌体 RNA 谱中，有 7 个 miRNA、3 个 lncRNA 和 83 个 mRNA 显著失调。当治疗有效和无效时，其调节趋势相反，呈现动态变化。经过验证，我们最终发现，当安罗替尼治疗有效时，血浆外泌体 lnc-SNAPC5-3:4 明显上调，当治疗失败时则明显下调（p < 0.05）。因此，它可以作为监测安罗替尼疗效的潜在生物标志物。
我们的研究结果表明，血浆外泌体 lnc-SNAPC5-3:4 具有作为监测安罗替尼疗效的生物标志物的潜力。
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