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HOXC8表达对骨肉瘤的预测潜力及致癌作用

The predictive potential and oncogenic effects of HOXC8 expression on osteosarcoma.

作者信息

Cheng Li, Wei Xiaojie, Zhao Keqi, Wu Fenzan, Lu Wenjie, Tong Songlin, Yu Guanzhen

机构信息

Department of Orthopaedics, Cixi People's Hospital, Wenzhou Medical University, Ningbo, Zhejiang, 315300, China.

Department of Oncology, Changzheng Hospital, Shanghai, 200433, China.

出版信息

Tumour Biol. 2016 Nov;37(11):14961-14967. doi: 10.1007/s13277-016-5384-4. Epub 2016 Sep 20.

Abstract

Homeobox C8 (HOXC8) has been implicated in cell growth, migration, and metastasis of various cancers, yet its role in osteosarcoma remains to be explored. In the present study, resected osteosarcoma specimens from 50 patients were enrolled to evaluate the expression of HOXC8 protein by immunohistochemistry (IHC). In vitro and in vivo assays were used to determine the effect of HOXC8 on cell growth, migration, and tumor growth. HOXC8 expression was observed in 31 (62.0 %) of the 50 primary tumors and significantly associated with poorly or un-differentiated specimens (P = 0.031) and larger tumor size (P = 0.049). Survival analysis demonstrated that HOXC8 is a candidate predictive factor in predicting patients' outcome and chemotherapeutic effect. HOXC8 knockdown led to inhibition of tumor cell proliferation and migration in vitro by inhibiting MMP-9 expression and tumor growth in vivo. Our results strongly suggest that HOXC8 is involved in the tumorigenesis of osteosarcoma and might serve as a novel predictor for patients' outcome.

摘要

同源框C8(HOXC8)与多种癌症的细胞生长、迁移和转移有关,但其在骨肉瘤中的作用仍有待探索。在本研究中,纳入了50例患者切除的骨肉瘤标本,通过免疫组织化学(IHC)评估HOXC8蛋白的表达。采用体外和体内试验来确定HOXC8对细胞生长、迁移和肿瘤生长的影响。在50个原发性肿瘤中有31个(62.0%)观察到HOXC8表达,且与低分化或未分化标本(P = 0.031)以及较大肿瘤大小(P = 0.049)显著相关。生存分析表明,HOXC8是预测患者预后和化疗效果的候选预测因子。HOXC8基因敲低通过抑制MMP - 9表达在体外导致肿瘤细胞增殖和迁移受到抑制,并在体内抑制肿瘤生长。我们的结果强烈表明,HOXC8参与骨肉瘤的肿瘤发生,可能作为患者预后的一种新的预测指标。

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