Araki Yoshihiro, Asano Naofumi, Yamamoto Norio, Hayashi Katsuhiro, Takeuchi Akihiko, Miwa Shinji, Igarashi Kentaro, Higuchi Takashi, Abe Kensaku, Taniguchi Yuta, Yonezawa Hirotaka, Morinaga Sei, Asano Yohei, Yoshida Takeshi, Hanayama Rikinari, Matsuzaki Juntaro, Ochiya Takahiro, Kawai Akira, Tsuchiya Hiroyuki
Department of Orthopedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan.
Oncol Lett. 2023 Apr 13;25(6):222. doi: 10.3892/ol.2023.13808. eCollection 2023 Jun.
In our previous study, osteosarcoma advanced locally, and metastasis was promoted through the secretion of large number of small extracellular vesicles, followed by suppressing osteoclastogenesis via the upregulation of microRNA (miR)-146a-5p. An additional 12 miRNAs in small extracellular vesicles were also detected ≥6× as frequently in high-grade malignancy with the capacity to metastasize as in those with a low metastatic potential. However, the utility of these 13 miRNAs for determining the prognosis or diagnosis of osteosarcoma has not been validated in the clinical setting. In the present study, the utility of these miRNAs as prognostic and diagnostic markers was therefore assessed. In total, 30 patients with osteosarcoma were retrospectively reviewed, and the survival rate was compared according to the serum miRNA levels in 27 patients treated with chemotherapy and surgery. In addition, to confirm diagnostic competency for osteosarcoma, the serum miRNA levels were compared with those in patients with other bone tumors (n=112) and healthy controls (n=275). The patients with osteosarcoma with high serum levels of several miRNAs (miR-146a-5p, miR-1260a, miR-487b-3p, miR-1260b and miR-4758-3p) exhibited an improved survival rate compared with those with low levels. In particular, patients with high serum levels of miR-1260a exhibited a significantly improved overall survival rate, metastasis-free survival rate and disease-free survival rate compared with those with low levels. Thus, serum miR-1260a may potentially be a prognostic marker for patients with osteosarcoma. Moreover, patients with osteosarcoma had higher serum miR-1261 levels than those with benign or intermediate-grade bone tumors and thus may be a potential therapeutic target, in addition to being useful for differentiating whether or not a bone tumor is high-grade. A larger investigation is required to clarify the actual utility of these miRNAs in the clinical setting.
在我们之前的研究中，骨肉瘤局部进展，并通过分泌大量小细胞外囊泡促进转移，随后通过上调微小RNA（miR）-146a-5p抑制破骨细胞生成。在小细胞外囊泡中还检测到另外12种miRNA，在具有转移能力的高级别恶性肿瘤中出现的频率至少是低转移潜能肿瘤中的6倍。然而，这13种miRNA在骨肉瘤预后或诊断中的应用尚未在临床环境中得到验证。因此，在本研究中评估了这些miRNA作为预后和诊断标志物的效用。总共对30例骨肉瘤患者进行了回顾性分析，并根据27例接受化疗和手术治疗患者的血清miRNA水平比较了生存率。此外，为了确认骨肉瘤的诊断能力，将血清miRNA水平与其他骨肿瘤患者（n = 112）和健康对照者（n = 275）的水平进行了比较。血清中几种miRNA（miR-146a-5p、miR-1260a、miR-487b-3p、miR-1260b和miR-4758-3p）水平高的骨肉瘤患者与水平低的患者相比，生存率有所提高。特别是，血清miR-1260a水平高的患者与水平低的患者相比，总生存率、无转移生存率和无病生存率均有显著提高。因此，血清miR-1260a可能是骨肉瘤患者的一种预后标志物。此外，骨肉瘤患者的血清miR-1261水平高于良性或中级骨肿瘤患者，因此除了有助于区分骨肿瘤是否为高级别外，还可能是一个潜在的治疗靶点。需要进行更大规模的研究以阐明这些miRNA在临床环境中的实际效用。
