Molecular characterization of the response to chemotherapy in conventional osteosarcomas: Predictive value of HSD17B10 and IFITM2
Molecular characterization of the response to chemotherapy in conventional osteosarcomas: Predictive value of HSD17B10 and IFITM2
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DOI：
10.1002/ijc.24457
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发表时间：
2009-08-15
影响因子：
6.4
通讯作者：
Bouvier, Corinne
中科院分区：
文献类型：
--
作者：
Salas, Sebastien;Jezequel, Pascal;Bouvier, Corinne
高级别骨肉瘤的治疗方案包括化疗、手术切除和术后化疗。根治性手术后的坏死程度仍然是唯一可靠的预后因素，并用于指导术后化疗的选择。本研究的目的是找到能够在开始治疗之前将骨肉瘤患者分类为对化疗反应良好或不良的分子标记。使用cDNA微阵列对20例非转移性高级别骨肉瘤患者进行基因表达筛查。使用 QRT-PCR 验证所选相关基因的表达。对 73 个活组织检查的组织微阵列切片进行免疫组织化学研究蛋白质表达。对RPL8基因进行荧光原位杂交。我们发现，HSD17B10 基因表达在反应不佳者中上调，并且治疗前活检中 HSD17B10 的免疫组织化学表达与化疗反应相关。其他结果包括 IFITM2、IFITM3 和 RPL8 基因表达与化疗反应的相关性。发现多体性 8 或 RPL8 增加与化疗良好反应之间存在统计相关性。这些数据表明HSD17B10、RPL8、IFITM2和IFITM3基因参与对化疗的反应，并且HSD17B10可能是治疗靶点。 RPL8 和 IFITM2 可能有助于诊断评估以及对参加随机试验的患者进行分层。 (C)2009年UICC
The therapy regimen of high-grade osteosarcoma includes chemotherapy followed by surgical resection and postoperative chemotherapy. The degree of necrosis following definitive surgery remains the only reliable prognostic factor and is used to guide the choice of postoperative chemotherapy. The aim of this study was to find molecular markers able to classify patients with an osteosarcoma as good or poor responders to chemotherapy before beginning treatment. Gene expression screening of 20 nonmetastatic high-grade osteosarcoma patients was performed using cDNA microarray. Expression of selected relevant genes was validated using QRT-PCR. Immunohistochemistry on tissue microarrays sections of 73 biopsies was performed to investigate protein expression. Fluorescent in situ hybridization was performed for RPL8 gene. We have found that HSD17B10 gene expression was up-regulated in poor responders and that immunohistochemistry expression of HSD17B10 on biopsy before treatment was correlated to response to chemotherapy. Other results include correlation of IFITM2, IFITM3, and RPL8 gene expression to chemotherapy response. A statistical correlation was found between polysomy 8 or gain of RPL8 and good response to chemotherapy. These data suggest that HSD17B10, RPL8, IFITM2, and IFITM3 genes are involved in the response to the chemotherapy and that HSD17B10 may be a therapeutic target. RPL8 and IFITM2 may be useful in the assessment at diagnosis and for stratifying patients taking part in randomized trials. (C) 2009 UICC