Identification of PHB2 as a Potential Biomarker of Luminal A Breast Cancer Cells Using a Cell-Specific Aptamer,ACS Applied Materials & Interfaces

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Identification of PHB2 as a Potential Biomarker of Luminal A Breast Cancer Cells Using a Cell-Specific Aptamer
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2022-11-08 , DOI: 10.1021/acsami.2c12291
Mei Liu _{1,

2,

3,

4} , Zhifei Wang ₂ , Song Li ₅ , Yan Deng ₅ , Nongyue He _{1,

5}

Affiliation

Precise diagnosis of breast cancer molecular subtypes remains a great challenge in clinics. The present molecular biomarkers are not specific enough to classify breast cancer subtypes precisely, which requests for more accurate and specific molecular biomarkers to be discovered. Aptamers evolved by the cell-systematic evolution of ligands by exponential enrichment (SELEX) method show great potential in the discovery and identification of cell membrane targets via aptamer-based cell membrane protein pull-down, which has been regarded as a novel and powerful weapon for the discovery and identification of new molecular biomarkers. Herein, a cell membrane protein PHB2 was identified as a potential molecular biomarker specifically expressed in the cell membranes of MCF-7 breast cancer cells using a DNA aptamer MF3Ec. Further experiments demonstrated that the PHB2 protein is differentially expressed in the cell membranes of MCF-7, SK-BR-3, and MDA-MB-231 breast cancer cells and MCF-10A cells, and the binding molecular domains of aptamer MF3Ec and anti-PHB2 antibodies to the PHB2 protein are different due to there being no obvious competitions between aptamer MF3Ec and anti-PHB2 antibodies in the binding to the cell membranes of target MCF-7 cells. Due to those four cells belonging to luminal A, HER2-positive, and triple-negative breast cancer cell subtypes and human normal mammary epithelial cells, respectively, the PHB2 protein in the cell membrane may be a potential biomarker for precise diagnosis of the luminal A breast cancer cell subtype, which is endowed with the ability to differentiate the luminal A breast cancer cell subtype from HER2-positive and triple-negative breast cancer cell subtypes and human normal mammary epithelial cells, providing a new molecular biomarker and therapeutic target for the accurate and precise classification and diagnostics and personalized therapy of breast cancer.

中文翻译：

使用细胞特异性适体鉴定 PHB2 作为 Luminal A 乳腺癌细胞的潜在生物标志物

乳腺癌分子亚型的精确诊断仍然是临床上的一大挑战。目前的分子生物标志物不够特异，无法对乳腺癌亚型进行精确分类，这就需要发现更准确、更特异的分子生物标志物。通过指数富集 (SELEX) 方法对配体进行细胞系统进化而进化出的适体在通过基于适体的细胞膜蛋白 pull-down 发现和鉴定细胞膜靶标方面显示出巨大的潜力，被认为是一种新颖而强大的武器用于发现和鉴定新的分子生物标志物。在此，使用 DNA 适体 MF3Ec 将细胞膜蛋白 PHB2 鉴定为在 MCF-7 乳腺癌细胞的细胞膜中特异性表达的潜在分子生物标志物。进一步的实验表明，PHB2蛋白在MCF-7、SK-BR-3、MDA-MB-231乳腺癌细胞和MCF-10A细胞的细胞膜中差异表达，适体MF3Ec和anti的结合分子域-针对 PHB2 蛋白的 PHB2 抗体是不同的，因为适体 MF3Ec 和抗 PHB2 抗体在与目标 MCF-7 细胞的细胞膜结合方面没有明显的竞争。由于这四种细胞分别属于luminal A、HER2阳性和三阴性乳腺癌细胞亚型和人正常乳腺上皮细胞，细胞膜中的PHB2蛋白可能是精确诊断luminal A的潜在生物标志物乳腺癌细胞亚型，

更新日期：2022-11-08

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