Cancer-Testis Antigens Expressed in Osteosarcoma Identified by Gene Microarray Correlate With A Poor Patient Prognosis
Cancer-Testis Antigens Expressed in Osteosarcoma Identified by Gene Microarray Correlate With A Poor Patient Prognosis
复制标题
通过基因微阵列鉴定骨肉瘤中表达的癌症睾丸抗原与患者不良预后相关
DOI：
10.1002/cncr.26486
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发表时间：
2012-04-01
期刊：
影响因子：
6.2
通讯作者：
Wang, Jin
中科院分区：
文献类型：
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作者：
Zou, Changye;Shen, Jingnan;Wang, Jin
背景：30% - 40%的骨肉瘤患者最终经历医疗失败；而且几乎没有确定有预后意义的生物标志物。像基因微阵列分析这样的高通量方法可以帮助识别分子生物标记物，这些标记物对骨肉瘤的诊断和靶向治疗非常有用。方法：采用寡核苷酸微阵列技术比较骨肉瘤细胞系和成骨细胞的表达谱。差异表达基因通过实时聚合酶链反应（PCR）分析证实。用流式细胞术和Western blot分析骨肉瘤细胞系中相应的蛋白，用免疫组化方法检测骨肉瘤组织中相应的蛋白。进一步分析染色强度与临床结果的关系。结果：癌睾丸抗原，包括黑色素瘤抗原家族A （MAGEA）、软骨肉瘤相关基因家族成员2 （CSAG2）和黑色素瘤优先表达抗原（PRAME），在分析的所有骨肉瘤细胞系中均显著升高。实时荧光定量PCR检测表明，癌睾丸抗原在骨肉瘤患者中表达频繁且协调。Western blot和流式细胞术分析证实了MAGEA在骨肉瘤细胞系中的表达。此外，免疫组织化学染色分析表明，MAGEA的表达可能用于预测远处转移和生存不良。magea阳性患者肺转移的校正相对危险度为2.79（95%可信区间为1.12-6.93;P = 0.028）。MAGEA表达患者和未表达患者的5年生存率分别为39.6% +/- 8.4%和80% +/- 8.9% （log-rank检验；P = 0.01）。结论：寡核苷酸微阵列、临床数据库和组织库的联合使用有助于鉴定分子肿瘤标志物。MAGEA和其他癌睾丸抗原在骨肉瘤中的频繁表达表明它们可能是有用的诊断标记和免疫治疗靶点，值得进一步研究。癌症2012;118:1845-55。(C) 2011年美国癌症协会。
BACKGROUND: From 30% to 40% patients with osteosarcoma eventually experience medical failure; and few biomarkers of prognostic significance have been established. High-throughput methods like gene microarray analysis can help to identify molecular biomarkers that are useful for diagnosing osteosarcoma and targeting its treatment. METHODS: Oligonucleotide microarrays were used to compare expression profiles of osteosarcoma cell lines and osteoblasts. Differentially expressed genes were confirmed by real-time polymerase chain reaction (PCR) analysis. Corresponding proteins were evaluated by flow cytometry and Western blot analysis in osteosarcoma cell lines and by immunohistochemistry in osteosarcoma tissues. The association between staining intensity and clinical outcome was analyzed further. RESULTS: Cancer-testis antigens, including melanoma antigen family A (MAGEA), chondrosarcoma-associated gene family, member 2 (CSAG2), and preferentially expressed antigen in melanoma (PRAME), were increased significantly in all osteosarcoma cell lines that were analyzed. Real-time PCR examinations indicated that cancer-testis antigen expression was frequent and coordinated in patients with osteosarcoma. The expression of MAGEA was confirmed by Western blot and flow cytometry analyses in osteosarcoma cell lines. Furthermore, immunohistochemical staining analysis suggested that MAGEA expression may be used to predict distant metastasis and poor survival. The adjusted relative risk for lung metastasis was 2.79 (95% confidence interval, 1.12-6.93; P = .028) for MAGEA-positive patients. Five-year survival rates for patients with and without MAGEA expression were 39.6% +/- 8.4% and 80% +/- 8.9%, respectively (log-rank test; P = .01). CONCLUSIONS: The combined use of an oligonucleotide microarray, a clinical database, and a tissue bank was useful for identifying molecular tumor markers. The frequent expression of MAGEA and other cancer-testis antigens in osteosarcoma indicates that they may be useful as diagnostic markers and targets of immunotherapy that warrant further investigation. Cancer 2012;118:1845-55. (C) 2011 American Cancer Society.