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Introduction
Osteosarcoma (OS) is one of the most prevalent types of malignant bone tumors, which predominantly occurs in adolescents and young adults; in addition, OS has a morbidity rate of ~5 cases per million (1). The conventional treatment of OS consists of surgery and radiotherapy; however, additional radiotherapy may not be used due to the risk of radiation-induced necrosis of surrounding structures (2). In addition, there is a high risk of relapse or metastasis for OS patients, even following curative resection; therefore, a substantial portion of patients with OS respond poorly to chemotherapy (3). Thus, elucidating the mechanisms underlying the metastasis of OS may lead to the development of novel therapeutic strategies for the treatment of OS.
Twist is a member of a highly conserved basic helix-loop-helix transcription factor family and is located on human chromosome 7 (4). It has been reported that Twist mediates cell migration and differentiation under various physiological conditions (5). In addition, Twist has been demonstrated to significantly enhance tumor malignancies, including breast cancer (6), hepatocellular carcinoma (HCC) (7) and prostate cancer (8). It was reported that the role of Twist in tumor cell invasion and metastasis may be associated with the regulation of cancer-associated functions, such as angiogenesis (9). Furthermore, Twist was found to regulate apoptosis and angiogenesis under a variety of pathological conditions (10). Therefore, it was hypothesized that Twist was closely correlated with malignant potential, progression and survival in patients with OS. However, to the best of our knowledge, there is limited information regarding the pathological roles of Twist expression in human OS tissues.
Angiogenesis is a key factor that mediates tumor metastasis; in addition, correlations between angiogenesis and patient survival in OS have been previously reported (11). Microvessel density (MVD) was demonstrated to be increased in histopathologically aggressive cancers, including esophageal squamous cell carcinoma (12) and mammary carcinoma (13). High MVD was also reported to be correlated with metastasis and poor survival in various types of cancer, such as OS (14). Increasing evidence has suggested that MVD may be considered an indirect marker of neoangiogenesis, which is commonly labeled by CD31 or CD34 (14).
Vascular endothelial growth factor (VEGF), the most important mediator of vascular formation, is essential for the initiation of immature vessel formation (15). VEGF...