Genetic and expression profiles of squamous cell carcinoma of the head and neck correlate with cisplatin sensitivity and resistance in cell lines and patients
Genetic and expression profiles of squamous cell carcinoma of the head and neck correlate with cisplatin sensitivity and resistance in cell lines and patients
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DOI：
10.1158/1078-0432.ccr-04-0722
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发表时间：
2004-12-15
影响因子：
11.5
通讯作者：
Teh, BT
中科院分区：
文献类型：
--
作者：
Akervall, J;Xiang, G;Teh, BT
目的：头颈部鳞状细胞癌（SCCHN）的治疗选择仍然主要基于肿瘤淋巴结转移分类。然而，有理由相信SCCHN的生物学特征可能与治疗反应独立相关。本研究的目的是检测可能与顺铂敏感性相关的遗传变化和基因表达谱[3- 10]。（4，5-二甲基噻唑-2-基）-2，5-二苯基溴化四唑鎓测定]。5个顺铂敏感细胞系和5个顺铂耐药细胞系[3-通过比较基因组杂交、光谱核型分析和cDNA微阵列分析（21，632个序列验证的人cDNA;通过逆转录酶-PCR对选定基因进行确认）研究了（4，5-二甲基噻唑-2-基）-2，5-二苯基四唑溴化物测定）。针对MET原癌基因在化疗敏感细胞系中低表达的情况，我们对29例接受诱导化疗的患者SCCHN进行免疫组化染色。这五个顺铂耐药细胞系显示出明显更多的遗传不平衡（缺失和扩增区域）和染色体异常，分别通过比较基因组杂交和光谱核型分析，比五种顺铂敏感细胞系的效果更好。微阵列研究发现了60个相似的基因，这些基因可以清楚地区分两组细胞系。已知这些基因中的一些涉及肿瘤进展、转移和耐药性。我们确定了低表达的c-met（免疫组化）作为一个预测因子，在nondiploid肿瘤（P = 0.026）的完全响应。结论：我们得出结论，顺铂的敏感性和耐药相关的显着差异，在个别SCCHN肿瘤细胞系和SCCHN患者的基因和表达谱。我们已经确定的基因可能作为新的治疗策略的潜在目标。
Purpose: The choice of treatment for squamous cell carcinoma of the head and neck (SCCHN) is still primarily based on the tumor-node-metastasis classification. However, it is reasonable to believe that biological profiles of SCCHN may be independently associated with response to therapy. The aim of the present study was to examine genetic changes and gene expression profiles that might correlate with sensitivity to cisplatin [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay] in 10 SCCHN cell lines.Experimental Design: Five cisplatin-sensitive and five cisplatin-resistant cell lines [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay] were studied by comparative genomic hybridization, spectral karyotyping, and cDNA microarray analysis (21,632 sequence-validated human cDNA; confirmation by reverse transcriptase-PCR for selected genes). For the MET proto-oncogene, which showed low expression in the chemosensitive cell lines, we did immunohistochemical staining on SCCHN of 29 patients who received induction chemotherapy.Results: The five cisplatin-resistant cell lines showed significantly more genetic imbalances (regions of loss and amplification) and chromosomal abnormalities by comparative genomic hybridization and spectral karyotyping, respectively, than did the five cisplatin-sensitive cell lines. Microarray studies identified similar to60 genes that clearly distinguish between the two groups of cell lines. Some of these genes are known to be involved in tumor progression, metastasis, and drug resistance. We identified low expression of c-met (immunohistochemistry) as a predictive factor for complete response in nondiploid tumors (P = 0.026).Conclusions: We conclude that cisplatin sensitivity and resistance are related to distinctive differences in the genetic and expression profiles in individual SCCHN tumor cell lines and in SCCHN patients. The genes we have identified may serve as potential targets for novel treatment strategies.