D'Amico Giuseppa, Santonocito Radha, Grech Godfrey, Graceffa Giuseppa, Cipolla Calogero, Scalia Federica, Raccosta Samuele, Manno Mauro, Conway de Macario Everly, Macario Alberto J L, Cappello Francesco, Rappa Francesca, Caruso Bavisotto Celeste, Campanella Claudia
Section of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy.
Department of Pathology, Faculty of Medicine and Surgery, University of Malta, MSD 2080 Msida, Malta.
Biology (Basel). 2024 Sep 22;13(9):743. doi: 10.3390/biology13090743.
The incidence of various types of cancer, for example, papillary thyroid carcinoma (PTC), is on the rise. Since therapeutic success depends greatly on early diagnosis, reliable diagnostic biomarkers must be identified, and easy-to-apply tools for detecting them must urgently be standardized. Here, we contribute to solving this medical challenge by assessing miRNAs suspected of promoting carcinogenesis in extracellular vesicles (EVs) that can be routinely obtained via liquid biopsy. We profit from current progress in cancerology that provides innovations in liquid biopsy and EVs analysis, along with the identification of miRNAs and chaperone system (CS) components implicated in carcinogenesis.
We measured in EVs obtained from circulating blood plasma from PTC patients the levels of three miRNAs implicated in thyroid cancer, hsa-miR-1-3p, hsa-miR-206, and hsa-miR-221-3p, and most likely involved in the regulation of two members of the CS, Hsp60 and CCT. EVs were isolated from the plasma of patients with PTC and controls with benign goiter (BG) and from the culture medium of a PTC cell line (MDAT32) and were appropriately characterized.
The levels of miRNAs determined by RT-qPCR were consistently higher in PTC patients and decreased down to control levels after thyroidectomy. Bioinformatics showed that the miRNAs target genes are associated with the molecular pathogenesis of PTC.
Our exploratory study reaffirms the potential in clinics of the selected miRNAs in EVs as useful biomarkers of PTC easily accessible via liquid biopsy, which is minimally invasive and amenable to periodic repetition, an improvement compared to the established fine-needle aspirate biopsy.
包括甲状腺乳头状癌（PTC）在内的各类癌症发病率正在上升。由于治疗成功很大程度上取决于早期诊断，因此必须识别可靠的诊断生物标志物，并且迫切需要规范易于应用的检测工具。在此，我们通过评估怀疑在细胞外囊泡（EV）中促进癌变的微小RNA（miRNA）来助力解决这一医学难题，这些细胞外囊泡可通过液体活检常规获取。我们受益于癌症学领域的当前进展，该进展在液体活检和EV分析方面带来了创新，同时还识别出了与癌变有关的miRNA和伴侣系统（CS）成分。
我们检测了从PTC患者循环血浆中获得的EV中三种与甲状腺癌相关的miRNA，即hsa-miR-1-3p、hsa-miR-206和hsa-miR-221-3p的水平，它们很可能参与了CS的两个成员热休克蛋白60（Hsp60）和TCP-1环状复合物（CCT）的调控。从PTC患者和良性甲状腺肿（BG）对照者的血浆以及PTC细胞系（MDAT32）的培养基中分离出EV，并对其进行了适当表征。
通过逆转录定量聚合酶链反应（RT-qPCR）测定的miRNA水平在PTC患者中始终较高，甲状腺切除术后降至对照水平。生物信息学表明，这些miRNA的靶基因与PTC的分子发病机制相关。
我们的探索性研究再次证实，EV中所选miRNA在临床上具有作为PTC有用生物标志物的潜力，可通过液体活检轻松获取，液体活检微创且可定期重复，与既定的细针穿刺活检相比有所改进。
