Liu Ming-Han, Cui You-Hong, Guo Qiao-Nan, Zhou Yue
Department of Orthopedics, Xinqiao Hospital, Third Military Medical University Chongqing 400037, China.
Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical UniversityChongqing 400038, China; Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Third Military Medical UniversityChongqing 400038, China.
Am J Cancer Res. 2016 Jun 1;6(6):1431-40. eCollection 2016.
Achaetescute-like 2 (ASCL2), a basic helix-loop-helix (bHLH) transcription factor, plays an important role in the determination of neuronal precursors in the central and peripheral nervous system and involves in tumor progression. However, the role of ASCL2 expression in the osteosarcoma prognosis has not been elaborated. This study aimed to evaluate ASCL2 expression level in osteosarcoma and assess its prognostic value for patients. ASCL2 protein expression was detected by immunohistochemistry (IHC) in 73 cases of osteosarcoma. Kaplan-Meier analysis and Cox regression analysis were performed to evaluate the prognostic significance of ASCL2. Immunohistochemistry analysis showed that the overall survival and metastasis-free survival of patients with positive ASCL2 expression were significantly shorter than patients with negative expression (both P<0.01). Multivariate Cox analysis identified ASCL2 expression as an independent prognostic factor to predict poor overall survival and metastasis-free survival (both P<0.01). Overexpression of ASCL2 expression greatly promoted cell proliferation and enhanced migration and invasion in vitro. This study indicates that increased expression of ASCL2 in primary osteosarcoma is a novel biomarker for predicting the development of metastases and poor outcomes of the patients.
无翅型无刚毛样蛋白2（ASCL2）是一种碱性螺旋-环-螺旋（bHLH）转录因子，在中枢和外周神经系统中神经前体细胞的决定过程中发挥重要作用，并且与肿瘤进展相关。然而，ASCL2表达在骨肉瘤预后中的作用尚未阐明。本研究旨在评估骨肉瘤中ASCL2的表达水平，并评估其对患者的预后价值。采用免疫组织化学（IHC）方法检测了73例骨肉瘤病例中ASCL2蛋白的表达。进行Kaplan-Meier分析和Cox回归分析以评估ASCL2的预后意义。免疫组织化学分析显示，ASCL2表达阳性患者的总生存期和无转移生存期显著短于表达阴性患者（均P<0.01）。多因素Cox分析确定ASCL2表达是预测总生存期和无转移生存期较差的独立预后因素（均P<0.01）。ASCL2表达的过表达在体外极大地促进了细胞增殖，并增强了迁移和侵袭能力。本研究表明，原发性骨肉瘤中ASCL2表达增加是预测转移发生和患者不良预后的一种新的生物标志物。
