Oncogene status predicts patterns of metastatic spread in treatment-naive nonsmall cell lung cancer.
Oncogene status predicts patterns of metastatic spread in treatment-naive nonsmall cell lung cancer.
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DOI：
10.1002/cncr.27409
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发表时间：
2012-09-15
期刊：
影响因子：
6.2
通讯作者：
Camidge DR
中科院分区：
文献类型：
--
作者：
Doebele RC;Lu X;Sumey C;Maxson DA;Weickhardt AJ;Oton AB;Bunn PA Jr;Barón AE;Franklin WA;Aisner DL;Varella-Garcia M;Camidge DR
以驱动癌基因激活为特征的非小细胞肺癌（NSCLC）不同亚群的发现极大地影响了个性化治疗。我们假设非小细胞肺癌的显性癌基因在诊断时与非小细胞肺癌的不同转移扩散模式有关。209例伴有EGFR突变（N=39）、KRAS突变（N=49）、ALK基因重排（N=41）或三种基因均为野生型（三阴性，N=80）的连续IV期非鳞状NSCLC患者纳入研究。在每个分子队列（EGFR、KRAS或ALK）和三阴性队列之间比较给定部位转移性疾病患者的百分比。ALK基因重排与心包疾病（OR=4.61, 95% CI 1.30, 16.37, p=0.02）和胸膜疾病（OR=4.80, 95% CI 2.10, 10.97, p<0.001）显著相关。与三阴性队列相比，ALK基因重排患者（OR=5.50, 95% CI 1.76, 17.18, p= 0.003）和EGFR突变患者（OR=5.17, 95% CI 1.63, 16.43, p= 0.006）更易发生肝转移。与三阴性队列相比，没有分子队列有肺结节、肾上腺、骨或脑转移的倾向。ALK重排队列中患者的平均转移性疾病位点数量显著大于三阴性队列（平均= 3.6个位点vs. 2.5个位点，p<0.0001）。这些结果支持了一种假设，即非小细胞肺癌的显性分子癌基因与不同的生物学行为相关，在诊断时表现为不同的转移扩散模式。
The discovery of distinct subsets of non-small cell lung cancer (NSCLC) characterized by activation of driver oncogenes has greatly impacted personalized therapy. We hypothesized that the dominant oncogene in NSCLC would be associated with distinct patterns of metastatic spread in NSCLC at the time of diagnosis. 209 consecutive patients with stage IV non-squamous NSCLC with an EGFR mutation (N=39), KRAS mutation (N=49), ALK gene rearrangement (N=41), or wild-type for all three (triple negative, N=80) were included. The percentage of patients with metastatic disease at a given site was compared between each molecular cohort (EGFR, KRAS, or ALK) and the triple negative cohort. ALK gene rearrangement was significantly associated with pericardial disease (OR=4.61, 95% CI 1.30, 16.37, p=0.02) and pleural disease (OR=4.80, 95% CI 2.10, 10.97, p<0.001). Patients with ALK gene rearrangements (OR=5.50, 95% CI 1.76, 17.18, p= 0.003) and patients with EGFR mutations (OR=5.17, 95% CI 1.63, 16.43, p= 0.006) were predisposed to liver metastasis compared to the triple negative cohort. No molecular cohort had a predisposition to pulmonary nodules, adrenal, bone, or brain metastasis compared to the triple negative cohort. The mean number of metastatic disease sites in patients within the ALK rearranged cohort was significantly greater than the triple negative cohort (mean = 3.6 sites vs. 2.5 sites, p<0.0001). The results support the hypothesis that the dominant molecular oncogenes in NSCLC are associated with different biological behaviors manifesting as distinct patterns of metastatic spread at the time of diagnosis.
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影响因子：
158.5
作者：
Lynch, TJ;Bell, DW;Haber, DA
通讯作者：
Haber, DA
影响因子：
50.3
作者：
Singh A;Greninger P;Rhodes D;Koopman L;Violette S;Bardeesy N;Settleman J
通讯作者：
Settleman J
影响因子：
--
作者：
Rossi, A;Manto, A;Gridelli, C
通讯作者：
Gridelli, C
影响因子：
45.3
作者：
Scagliotti, Giorgio Vittorio;Parikh, Purvish;Gandara, David
通讯作者：
Gandara, David
影响因子：
158.5
作者：
Sandler, Alan;Gray, Robert;Johnson, David H.
通讯作者：
Johnson, David H.