Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
Oncologist. 2012;17(5):653-62. doi: 10.1634/theoncologist.2010-0379. Epub 2012 Apr 24.
To improve the clinical outcome of patients with gastric cancer, intensified combination strategies are currently in clinical development, including combinations of more extensive surgery, (neo)adjuvant chemotherapy, and radiotherapy. The present study used DNA copy number profiling to identify subgroups of patients with different clinical outcomes. We hypothesize that, by identification of subgroups, individual treatment strategies can be selected to improve clinical outcome and to reduce unnecessary treatment toxicity for patients with gastric cancer.
DNA from 206 gastric cancer patients was isolated and analyzed by genomewide array comparative genomic hybridization. DNA copy number profiles were correlated with lymph node status and patient survival. In addition, heat shock protein 90 (HSP90) expression was analyzed and correlated with survival in 230 gastric cancer patients.
Frequent (>20%) DNA copy number gains and losses were observed on several chromosomal regions. Losses on 5q11.2-q31.3 and 14q32.11-q32.33 (14% of patients) were correlated with good clinical outcome in univariate and multivariate analyses, with a median disease-free survival interval of 9.2 years. In addition, loss of expression of HSP90, located on chromosome 14q32.2, was correlated with better patient survival.
Genomewide DNA copy number profiling allowed the identification of a subgroup of gastric cancer patients, marked by losses on chromosomes 5q11.2-q31.3 and 14q32.11-q32.33 or low HSP90 protein expression, with an excellent clinical outcome after surgery alone. We hypothesize that this subgroup of patients most likely will not benefit from (neo)adjuvant systemic treatment and/or radiotherapy, whereas anti-HSP90 therapy may have clinical potential in patients with HSP90-expressing gastric cancer, pending validation in an independent dataset.
为了改善胃癌患者的临床结局，目前正在临床开发强化联合策略，包括更广泛的手术、（新）辅助化疗和放疗的联合。本研究使用 DNA 拷贝数谱分析来鉴定具有不同临床结局的患者亚组。我们假设，通过鉴定亚组，可以选择个体化治疗策略，以改善临床结局并减少胃癌患者不必要的治疗毒性。
从 206 例胃癌患者中分离出 DNA，并通过全基因组阵列比较基因组杂交进行分析。将 DNA 拷贝数谱与淋巴结状态和患者生存相关联。此外，还分析了 230 例胃癌患者的热休克蛋白 90（HSP90）表达，并与生存相关联。
在多个染色体区域观察到频繁（>20%）的 DNA 拷贝数增益和丢失。染色体 5q11.2-q31.3 和 14q32.11-q32.33 上的缺失（14%的患者）与单变量和多变量分析中的良好临床结局相关，无病生存间隔中位数为 9.2 年。此外，位于染色体 14q32.2 上的 HSP90 表达缺失与患者生存更好相关。
全基因组 DNA 拷贝数谱分析可鉴定出一组胃癌患者，其特征是染色体 5q11.2-q31.3 和 14q32.11-q32.33 缺失或 HSP90 蛋白表达低，单独手术后临床结局极佳。我们假设，这组患者很可能不会从（新）辅助全身治疗和/或放疗中获益，而 HSP90 表达阳性的胃癌患者的 HSP90 治疗可能具有临床潜力，但需要在独立数据集进行验证。
