Identification of urine protein biomarkers with the potential for early detection of lung cancer.
Identification of urine protein biomarkers with the potential for early detection of lung cancer.
复制标题
鉴定具有早期检测肺癌潜力的尿蛋白生物标志物。
DOI：
10.1038/srep11805
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发表时间：
2015-07-02
影响因子：
4.6
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Zhang H;Cao J;Li L;Liu Y;Zhao H;Li N;Li B;Zhang A;Huang H;Chen S;Dong M;Yu L;Zhang J;Chen L
肺癌是癌症相关死亡的主要原因，总体5年生存率低于15%。大规模的临床试验表明，低剂量计算机断层扫描筛查可显著降低高危人群的死亡率。然而，临床上迫切需要能够识别最高危人群并在临床表现之前检测肺癌的生物标志物。在这里，我们报告了能够检测肺癌的尿液生物标志物的鉴定。使用特征良好的诱导型Kras（G12D）肺癌小鼠模型，我们确定了与同胞对照组相比，荷瘤小鼠尿液蛋白质组的改变。在患者的尿液和健康人群对照之间也检测到蛋白质组水平的显著差异。重要的是，我们鉴定了7种通常在荷瘤小鼠和患者中显著上调的蛋白质。在一个独立的队列中，我们发现7种蛋白质中有2种在肺癌患者的尿样中上调，而在对照组中则没有。这些蛋白质的动力学与小鼠模型中的疾病状态相关。这些肿瘤生物标志物可能有助于肺癌的早期检测。
Lung cancer is the leading cause of cancer-related deaths and has an overall 5-year survival rate lower than 15%. Large-scale clinical trials have demonstrated a significant relative reduction in mortality in high-risk individuals with low-dose computed tomography screening. However, biomarkers capable of identifying the most at-risk population and detecting lung cancer before it becomes clinically apparent are urgently needed in the clinic. Here, we report the identification of urine biomarkers capable of detecting lung cancer. Using the well-characterized inducible Kras (G12D) mouse model of lung cancer, we identified alterations in the urine proteome in tumor-bearing mice compared with sibling controls. Marked differences at the proteomic level were also detected between the urine of patients and that of healthy population controls. Importantly, we identified 7 proteins commonly found to be significantly up-regulated in both tumor-bearing mice and patients. In an independent cohort, we showed that 2 of the 7 proteins were up-regulated in urine samples from lung cancer patients but not in those from controls. The kinetics of these proteins correlated with the disease state in the mouse model. These tumor biomarkers could potentially aid in the early detection of lung cancer.
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有效使用 PI3K 和 MEK 抑制剂治疗突变型 Kras G12D 和 PIK3CA H1047R 小鼠肺癌。
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
8
作者：
Ji, H;Houghton, AM;Wong, KK
通讯作者：
Wong, KK
影响因子：
8.8
作者：
Knekt, P;Aromaa, A;Maatela, J;Rissanen, A;Hakama, M;Aaran, R K;Nikkari, T;Hakulinen, T;Peto, R;Teppo, L
通讯作者：
Teppo, L
影响因子：
28.2
作者：
Ellis MJ;Gillette M;Carr SA;Paulovich AG;Smith RD;Rodland KK;Townsend RR;Kinsinger C;Mesri M;Rodriguez H;Liebler DC;Clinical Proteomic Tumor Analysis Consortium (CPTAC)
通讯作者：
Clinical Proteomic Tumor Analysis Consortium (CPTAC)
影响因子：
254.7
作者：
Siegel, Rebecca;Naishadham, Deepa;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin