骨肉瘤中高迁移率族 AT 钩结构域 2（HMGA2）的表达及临床意义。
Expression and Clinical Significance of High-Mobility Group AT-hook 2 (HMGA2) in Osteosarcoma.
机构信息
Department of Orthopedic Surgery, The First Affiliated Hospital of University of South China, Hengyang, China.
Department of Orthopedic Surgery, Sarcoma Biology Laboratory, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
出版信息
Orthop Surg. 2022 May;14(5):955-966. doi: 10.1111/os.13167. Epub 2022 Apr 7.
OBJECTIVE
Although high-mobility group AT-hook 2 (HMGA2) has been shown to have crucial roles in the pathogenesis and metastasis of various malignancies, its expression and significance in osteosarcoma remain unknown. Here we evaluate the expression, clinical prognostic value, and overall function of HMGA2 in osteosarcoma.
METHODS
Sixty-nine osteosarcoma patient specimens within a tissue microarray (TMA) were analyzed by immunohistochemistry for HMGA2 expression. Demographics and clinicopathological information including age, gender, tumor location, metastasis, recurrence, chemotherapy response, follow-up time, and disease status were also collected. After validation of expression, we determined whether there was a correlation between HMGA2 expression and patient clinicopathology. HMGA2 expression was also evaluated in osteosarcoma cell lines and patient tissues by Western blot, we analyzed the expression of HMGA2 in the human osteosarcoma cell lines MG63, 143B, U2OS, Saos-2, MNNG/HOS, and KHOS. HMGA2-specific siRNA and clonogenic assays were then used to determine the effect of HMGA2 inhibition on osteosarcoma cell proliferation, growth, and chemosensitivity.
RESULTS
HMGA2 expression was elevated in the osteosarcoma patient specimens and human osteosarcoma cell lines. HMGA2 was differentially expressed in human osteosarcoma cell lines. Specifically, a relatively high expression of HMGA2 was present in KHOS, MNNG/HOS, 143B and a relatively low expression was in MG63, U2OS as well as Saos-2. HMGA2 expression is correlated with metastasis and shorter overall survival. High HMGA2 expression is an independent predictor of poor osteosarcoma prognosis. There was no significant correlation between HMGA2 expression and the age, gender, or tumor site of the patient. HMGA2 expression is predominantly within the nucleus. The expression of HMGA2 also directly correlated to neoadjuvant chemoresistance. There was a significant reduction of HMGA2 expression in the siRNA transfection group. After the use of siRNA, the proliferation of osteosarcoma cells is decreased and the chemosensitivity of osteosarcoma cells is significantly increased.
CONCLUSION
Our study supports HMGA2 as a potential prognostic biomarker and therapeutic target in osteosarcoma.
目的
尽管高迁移率族 AT 钩 2（HMGA2）已被证明在多种恶性肿瘤的发病机制和转移中具有关键作用，但它在骨肉瘤中的表达和意义尚不清楚。在这里，我们评估了 HMGA2 在骨肉瘤中的表达、临床预后价值和整体功能。
方法
通过免疫组织化学分析 69 例组织微阵列（TMA）中的骨肉瘤患者标本中 HMGA2 的表达。还收集了人口统计学和临床病理信息，包括年龄、性别、肿瘤部位、转移、复发、化疗反应、随访时间和疾病状态。在验证表达后，我们确定 HMGA2 表达与患者临床病理之间是否存在相关性。还通过 Western blot 检测了 HMGA2 在骨肉瘤细胞系和患者组织中的表达，分析了人骨肉瘤细胞系 MG63、143B、U2OS、Saos-2、MNNG/HOS 和 KHOS 中 HMGA2 的表达。然后使用 HMGA2 特异性 siRNA 和集落形成测定来确定 HMGA2 抑制对骨肉瘤细胞增殖、生长和化疗敏感性的影响。
结果
HMGA2 在骨肉瘤患者标本和人骨肉瘤细胞系中表达升高。HMGA2 在人骨肉瘤细胞系中差异表达。具体来说，KHOS、MNNG/HOS、143B 中 HMGA2 的表达相对较高，而 MG63、U2OS 和 Saos-2 中 HMGA2 的表达相对较低。HMGA2 表达与转移和总生存期较短相关。高 HMGA2 表达是骨肉瘤预后不良的独立预测因子。HMGA2 表达与患者的年龄、性别或肿瘤部位之间没有显著相关性。HMGA2 表达主要位于细胞核内。HMGA2 的表达也与新辅助化疗耐药性直接相关。在 siRNA 转染组中，HMGA2 的表达显著降低。使用 siRNA 后，骨肉瘤细胞的增殖减少，骨肉瘤细胞的化疗敏感性显著增加。
结论
我们的研究支持 HMGA2 作为骨肉瘤中潜在的预后生物标志物和治疗靶点。
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