Lv Ruichan, Wang Yanxing, Lin Bi, Peng Xiangrong, Liu Jun, Lü Wei-Dong, Tian Jie
Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an, Shanxi 710071, China.
Department of Thoracic Surgery, Tumor Hospital of Shaanxi Province, Affiliated to the Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi Province 710061, China.
Anal Chem. 2021 Mar 23;93(11):4984-4992. doi: 10.1021/acs.analchem.1c00374. Epub 2021 Mar 11.
In this research, the antibody of the searched hub genes has been proposed to combine with a rare-earth composite for an upconversion luminescence (UCL) and downconversion (DCL) NIR-II imaging strategy for the diagnosis of lung adenocarcinoma (LUAD). Weighted gene co-expression network analysis is used to search the most relevant hub genes, and the required top genes that contribute to tumorigenesis (negative: CLEC3B, MFAP4, PECAM1, and FHL1; positive: CCNB2, CDCA5, HMMR, and TOP2A) are identified and validated by survival analysis and transcriptional and translational results. Meanwhile, fluorescence imaging probes (NaYF:Yb,Er,Eu@NaYF:Nd, denoted as NYF:Eu NPs) with multimodal optical imaging properties of downconversion and upconversion luminescence in the visible region and luminescence in the near infrared II region are designed with various uniform sizes and enhanced penetration and sensitivity. Finally, when the NYF:Eu NP probe is combined with antibodies of these chosen positive hub genes (such as, TOP2A and CCNB2), the and animal experiments (flow cytometry, cell counting kit-8 assay using A549 cells, and immunohistochemistry IHC microscopy images of LUAD from patient cases) indicate that the designed nanoprobes can be excellently used as a targeted optical probe for future accurate diagnosis and surgery navigation of LUAD in contrast with other cancer cells and normal cells. This strategy of antibodies combined with optical probes provides a dual-modal luminescence imaging method for precise medicine.
在本研究中,已提出将所搜索到的枢纽基因的抗体与一种稀土复合材料结合,用于上转换发光(UCL)和下转换(DCL)近红外二区成像策略,以诊断肺腺癌(LUAD)。使用加权基因共表达网络分析来搜索最相关的枢纽基因,并通过生存分析以及转录和翻译结果确定并验证了对肿瘤发生有贡献的所需顶级基因(阴性:CLEC3B、MFAP4、PECAM1和FHL1;阳性:CCNB2、CDCA5、HMMR和TOP2A)。同时,设计了具有可见区域下转换和上转换发光以及近红外二区发光的多模态光学成像特性的荧光成像探针(NaYF:Yb,Er,Eu@NaYF:Nd,记为NYF:Eu NPs),其具有各种均匀尺寸且具有增强的穿透性和灵敏度。最后,当NYF:Eu NP探针与这些选定的阳性枢纽基因(如TOP2A和CCNB2)的抗体结合时,动物实验(流式细胞术、使用A549细胞的细胞计数试剂盒 - 8检测以及来自患者病例的LUAD免疫组织化学IHC显微镜图像)表明,与其他癌细胞和正常细胞相比,所设计的纳米探针可以出色地用作未来LUAD精确诊断和手术导航的靶向光学探针。这种抗体与光学探针结合的策略为精准医学提供了一种双模态发光成像方法。