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一种选择性靶向肺癌血清的新型DNA适配体的鉴定。

Identification of a novel DNA aptamer that selectively targets lung cancer serum.

作者信息

Zhao Yunwang, He Lei, Huang Baihai, Zhang Weidong, Hu Ailing, Li Baolin, Liao Shiqi, Wang Na

机构信息

The First Hospital of Qinhuangdao Qinhuangdao 066000 China

Guangdong Provincial Key Laboratory of Synthetic Genomics, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences Shenzhen 518055 China.

出版信息

RSC Adv. 2021 Oct 15;11(53):33759-33769. doi: 10.1039/d1ra06233f. eCollection 2021 Oct 8.

Abstract

Lung cancer is the leading cause of cancer-related deaths worldwide. Early diagnosis and treatment is critical to improving the 5 year survival rate of lung cancer. The identification of new options for early-stage diagnosis and therapy of lung cancer still represents a crucial challenge. Therefore, a new diagnostic method is urgently needed. In this study, we used a new modified SELEX, called serum-SELEX, to isolate aptamers that can specifically bind lung cancer serum, without any prior knowledge of their target. Among the obtained candidate aptamer sequences, Ap-LC-19 was identified as the optimal aptamer probe with the lowest dissociation constant ( ) value of 15 ± 8.6 nM and higher affinity assessed by qPCR. Furthermore, this molecule could be a suitable aptamer for lung cancer serum and could be used as a recognition element in aptamer-based biosensors for efficient early diagnosis of lung cancer or as an innovative tool for targeted therapy. In addition, we performed MALDI-TOF MS followed by secondary peptide sequencing MS analysis for the identification of the aptamer targeted proteins. CLEC3B could be useful biomarkers for early detection of lung cancer and in monitoring its evolution.

摘要

肺癌是全球癌症相关死亡的主要原因。早期诊断和治疗对于提高肺癌的5年生存率至关重要。确定肺癌早期诊断和治疗的新方法仍然是一项关键挑战。因此,迫切需要一种新的诊断方法。在本研究中,我们使用了一种新的改良SELEX,即血清SELEX,来分离能够特异性结合肺癌血清的适配体,而无需事先了解其靶标。在获得的候选适配体序列中,Ap-LC-19被鉴定为最佳适配体探针,其解离常数()值最低,为15±8.6 nM,通过qPCR评估具有更高的亲和力。此外,该分子可能是一种适用于肺癌血清的适配体,可作为基于适配体的生物传感器中的识别元件,用于肺癌的高效早期诊断,或作为靶向治疗的创新工具。此外,我们进行了基质辅助激光解吸电离飞行时间质谱(MALDI-TOF MS),随后进行二级肽测序质谱分析,以鉴定适配体靶向的蛋白质。CLEC3B可能是肺癌早期检测及其进展监测的有用生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d1b/9042271/24968eb3a988/d1ra06233f-s1.jpg

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