肺癌的基因组学和蛋白组学研究PPT.ppt

我们能否应用分子标记物指导NSCLC的治疗? 除非预后因子是治疗相关的，否则很难应用于临床。 目前为止，大多数被认识的标记物尚无确定的治疗相关性。 有效性确认的金标准包括对预期自然增加的患者样本的实时分析。 NSCLC中分子标记物总结 很少有研究比较基因表达与传统预测因子（如年龄、性别、肿瘤分期及组织学特点等）预测作用的差异。 要警惕对基因组学或蛋白组学检测的全盘接受。 相关研究表明已切除的早期NSCLC是提供生物样本的最好时机。 三基因预后分类S.K. Lau et al. J Clin Oncol 25:5562, 2007 Stage I Stage II All patients ERCC1 预后因子G. Simon et al. Chest 127:978, 2005 ERCC1 50 = 94.6 mo ERCC1 ≤ 50 = 35.5 mo p = 0.01 ERCC1 与 特异性临床预测因子的关系 Factor: Early Stage NSCLC Survival ERCC1 SqCC: ? ? Adeno: ? ? Stage I: ? ? Stages II/III: ? ? Never Smoker: ? ? LVI: ? ? VPI: ? ? Data taken from: NEJM 355:983, 2006; Chest 127:978, 2005 从基因到蛋白 “DNA makes RNA, RNA makes protein, and protein makes us.” - Francis Crick, ca. 1957 基因组学还是蛋白组学? “Good” “Bad” NSCLC中的血清蛋白组学来自EGFR TKI的结果 已切除的 I 期NSCLC蛋白组学预测分类 已切除的 I期NSCLC 患者的疾病特异性生存 0 0.2 0.4 0.6 0.8 1 0 20 40 60 80 100 120 140 Predicted Resistant (N = 22) Predicted Sensitive (N = 22) No Adjuvant Chemotherapy Has helped improve our understanding of the histological heterogeneity of NSCLC. Has identified potential biomarkers gene signatures for classifying patients with significantly different survival outcomes. However, the performance general applicability of published classifiers has not been easy to establish because of small numbers of subjects examined inclusion of heterogeneous tumor types. Furthermore, there have not been uniform criteria for sample inclusion, annotation, sample processing data analyses. Global gene-expression profiling using microarray technologies Gene Expression-based Survival Prediction in Lung AdenocarcinomaK. Shedden et al. Nat Med 14:822, 2008 A significant degree of outcome prediction accuracy was observed using gene expression data alone; however, the hazard ratios for most prediction models increased with the inclusion of clinical data. Conversely, gene expression data improved the predictive performance of clinical parameters alone (AJCC stage (coded as 1, 2, 3/4), gender, age). 什么样的标记物是合适的? R. Simon. Nat Clin Prac Onc