Urla Cristian, Stagno Matias Julian, Schmidt Andreas, Handgretinger Rupert, Fuchs Jörg, Warmann Steven W, Schmid Evi
Department of Pediatric Surgery and Pediatric Urology, University Children's Hospital of Tuebingen, 72076 Tuebingen, Germany.
Department of Pediatric Hematology and Oncology, University Children's Hospital of Tuebingen, 72076 Tuebingen, Germany.
Biomedicines. 2022 Jul 28;10(8):1812. doi: 10.3390/biomedicines10081812.
Biomarkers allowing characterization of pediatric rhabdomyosarcoma (RMS) are lacking. Epitope detection in monocytes (EDIM) is a novel method focused on detection of the biomarkers TKTL1 (transketolase-like protein 1) and Apo10 (epitope of DNaseX) in activated monocytes (CD14/CD16) from patient's blood. We investigated the expression of these biomarkers in RMS cell lines, tumor material, and peripheral blood from RMS patients. Expression levels of TKTL1 and DNaseX/Apo10 in RMS cell lines (RH30, RD) and tumor samples were analyzed by RT-PCR and flow cytometry. Blood samples of 29 RMS patients were measured and compared to 27 healthy individuals. The percentages of activated CD14/CD16 monocytes harboring TKTL1 and Apo10 were determined. EDIM-TKTL1 and EDIM-Apo10 expression scores were calculated. The relationship between TKTL1 expression and DNA-hypomethylation was evaluated. Both RMS cell lines and tumor samples showed significantly higher expression levels of TKTL1 and DNaseX/Apo10 compared to skeletal muscle cells (SkMC). EDIM-TKTL1 and EDIM-Apo10 scores were positive in 96.5% of patients with RMS. All healthy controls had negative corresponding scores. RMS cell lines show increased expression levels of the biomarkers TKTL1 and DNaseX/Apo10. The sensitivity of the EDIM blood test indicates that this assay might serve as an additional tool in pediatric RMS.
目前尚缺乏能够对小儿横纹肌肉瘤（RMS）进行特征描述的生物标志物。单核细胞表位检测（EDIM）是一种新方法，专注于检测患者血液中活化单核细胞（CD14/CD16）中的生物标志物转酮醇酶样蛋白1（TKTL1）和DNaseX表位10（Apo10）。我们研究了这些生物标志物在RMS细胞系、肿瘤组织以及RMS患者外周血中的表达情况。通过逆转录聚合酶链反应（RT-PCR）和流式细胞术分析了RMS细胞系（RH30、RD）和肿瘤样本中TKTL1和DNaseX/Apo10的表达水平。对29例RMS患者的血样进行了检测，并与27名健康个体进行比较。测定了携带TKTL1和Apo10的活化CD14/CD16单核细胞的百分比。计算了EDIM-TKTL1和EDIM-Apo10表达评分。评估了TKTL1表达与DNA低甲基化之间的关系。与骨骼肌细胞（SkMC）相比，RMS细胞系和肿瘤样本中TKTL1和DNaseX/Apo10的表达水平均显著更高。96.5%的RMS患者EDIM-TKTL1和EDIM-Apo10评分呈阳性。所有健康对照的相应评分均为阴性。RMS细胞系中生物标志物TKTL1和DNaseX/Apo10的表达水平升高。EDIM血液检测敏感性表明该检测方法可能成为小儿RMS的一种辅助工具。
