Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
PLoS One. 2012;7(12):e51713. doi: 10.1371/journal.pone.0051713. Epub 2012 Dec 17.
Brain metastasis (BM) from non-small cell lung cancer (NSCLC) is relatively common, but identifying which patients will develop brain metastasis has been problematic. We hypothesized that genotype variants in the TGF-β signaling pathway could be a predictive biomarker of brain metastasis.
We genotyped 33 SNPs from 13 genes in the TGF-β signaling pathway and evaluated their associations with brain metastasis risk by using DNA from blood samples from 161 patients with NSCLC. Kaplan-Meier analysis was used to assess brain metastasis risk; Cox hazard analyses were used to evaluate the effects of various patient and disease characteristics on the risk of brain metastasis.
The median age of the 116 men and 45 women in the study was 58 years; 62 (39%) had stage IIIB or IV disease. Within 24 months after initial diagnosis of lung cancer, brain metastasis was found in 60 patients (37%). Of these 60 patients, 16 had presented with BM at diagnosis. Multivariate analysis showed the GG genotype of SMAD6: rs12913975 and TT genotype of INHBC: rs4760259 to be associated with a significantly higher risk of brain metastasis at 24 months follow-up (hazard ratio [HR] 2.540, 95% confidence interval [CI] 1.204-5.359, P = 0.014; and HR 1.885, 95% CI 1.086-3.273, P = 0.024), compared with the GA or CT/CC genotypes, respectively. When we analyzed combined subgroups, these rates showed higher for those having both the GG genotype of SMAD6: rs12913975 and the TT genotype of INHBC: rs4760259 (HR 2.353, 95% CI 1.390-3.985, P = 0.001).
We found the GG genotype of SMAD6: rs12913975 and TT genotype of INHBC: rs4760259 to be associated with risk of brain metastasis in patients with NSCLC. This finding, if confirmed, can help to identify patients at high risk of brain metastasis.
非小细胞肺癌（NSCLC）脑转移较为常见，但确定哪些患者会发生脑转移一直是个问题。我们假设 TGF-β 信号通路中的基因型变异可能是脑转移的预测生物标志物。
我们对 13 个 TGF-β 信号通路基因中的 33 个 SNP 进行了基因分型，并使用来自 161 例 NSCLC 患者的血液样本中的 DNA 评估了它们与脑转移风险的相关性。采用 Kaplan-Meier 分析评估脑转移风险；采用 Cox 风险分析评估各种患者和疾病特征对脑转移风险的影响。
研究中 116 名男性和 45 名女性的中位年龄为 58 岁；62 例（39%）患有 IIIB 或 IV 期疾病。在肺癌初始诊断后 24 个月内，60 例患者（37%）发现脑转移。在这 60 例患者中，16 例在诊断时即出现 BM。多变量分析显示，SMAD6：rs12913975 的 GG 基因型和 INHBC：rs4760259 的 TT 基因型与 24 个月随访时脑转移的风险显著增加相关（风险比 [HR] 2.540，95%置信区间 [CI] 1.204-5.359，P=0.014；和 HR 1.885，95% CI 1.086-3.273，P=0.024），与 GA 或 CT/CC 基因型相比。当我们分析联合亚组时，这些比率在同时具有 SMAD6：rs12913975 的 GG 基因型和 INHBC：rs4760259 的 TT 基因型的患者中更高（HR 2.353，95% CI 1.390-3.985，P=0.001）。
我们发现 SMAD6：rs12913975 的 GG 基因型和 INHBC：rs4760259 的 TT 基因型与 NSCLC 患者的脑转移风险相关。如果这一发现得到证实，可以帮助识别高风险脑转移的患者。
