Prognostic PET 18F-FDG uptake imaging features are associated with major oncogenomic alterations in patients with resected non-small cell lung cancer.
Prognostic PET 18F-FDG uptake imaging features are associated with major oncogenomic alterations in patients with resected non-small cell lung cancer.
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DOI：
10.1158/0008-5472.can-11-3943
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发表时间：
2012-08-01
期刊：
影响因子：
11.2
通讯作者：
Plevritis SK
中科院分区：
文献类型：
--
作者：
Nair VS;Gevaert O;Davidzon G;Napel S;Graves EE;Hoang CD;Shrager JB;Quon A;Rubin DL;Plevritis SK
虽然正电子发射断层扫描（PET）期间的18f -2-氟-2-脱氧葡萄糖（FDG）摄取可以预测非小细胞肺癌（NSCLC）患者的术后预后，但这一观察的生物学基础尚不完全清楚。在这里，我们分析了来自非小细胞肺癌患者的25个肿瘤，以确定肿瘤18F-FDG PET摄取特征与基因表达特征和生存相关。描述FDG摄取的14个定量PET成像特征与单个基因和共表达基因簇（元基因）的基因表达相关。对于每个FDG摄取特征，导出了相关的元基因特征，并在非小细胞肺癌患者的外部验证队列中确定了预后模型并进行了测试。与FDG摄取相关的8个单基因中的4个（LY6E、RNF149、MCM6、FAP）也与生存相关。最具预后的元基因特征与多变量FDG摄取特征（SUVmax， SUVvariance和SUVPCA2）相关，它们分别与外部队列（HR 5.87，可信区间[CI] 2.49-13.8）和验证队列（HR 6.12, CI 1.08-34.8）的生存率高度相关。细胞周期、增殖、死亡和自我识别途径在放射基因组谱中发生改变。总之，我们的研究结果表明，利用肿瘤基因组学和扩展的PET-FDG成像特征集合可以增强我们对FDG摄取作为一种成像生物标志物的理解，而不仅仅是它与糖酵解的关联。
Although 18F-2-fluoro-2-deoxyglucose (FDG) uptake during positron emission tomography (PET) predicts post-surgical outcome in patients with non-small-cell lung cancer (NSCLC), the biologic basis for this observation is not fully understood. Here we analyzed 25 tumors from NSCLC patients to identify tumor 18F-FDG PET uptake features associated with gene expression signatures and survival. Fourteen quantitative PET imaging features describing FDG uptake were correlated with gene expression for single genes and co-expressed gene clusters (metagenes). For each FDG uptake feature, an associated metagene signature was derived and a prognostic model was identified in an external and tested in a validation cohort of NSCLC patients. Four of 8 single genes associated with FDG uptake (LY6E, RNF149, MCM6, FAP) were also associated with survival. The most prognostic metagene signature was associated with a multivariate FDG uptake feature (SUVmax, SUVvariance and SUVPCA2), each highly associated with survival in the external (HR 5.87, confidence interval [CI] 2.49-13.8) and validation (HR 6.12, CI 1.08-34.8) cohorts, respectively. Cell cycle, proliferation, death, and self-recognition pathways were altered in this radiogenomic profile. Together, our findings suggest that leveraging tumor genomics with an expanded collection of PET-FDG imaging features may enhance our understanding of FDG uptake as an imaging biomarker beyond its association with glycolysis.