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首页> 外文期刊>International Journal of Molecular Sciences >Preliminary Evidence on the Diagnostic and Molecular Role of Circulating Soluble EGFR in Non-Small Cell Lung Cancer
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Preliminary Evidence on the Diagnostic and Molecular Role of Circulating Soluble EGFR in Non-Small Cell Lung Cancer

机译：循环可溶性EGFR在非小细胞肺癌中的诊断和分子作用的初步证据

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Assessment of biological diagnostic factors providing clinically-relevant information to guide physician decision-making are still needed for diseases with poor outcomes, such as non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) is a promising molecule in the clinical management of NSCLC. While the EGFR transmembrane form has been extensively investigated in large clinical trials, the soluble, circulating EGFR isoform (sEGFR), which may have a potential clinical use, has rarely been considered. This study investigates the use of sEGFR as a potential diagnostic biomarker for NSCLC and also characterizes the biological function of sEGFR to clarify the molecular mechanisms involved in the course of action of this protein. Plasma sEGFR levels from a heterogeneous cohort of 37 non-advanced NSCLC patients and 54 healthy subjects were analyzed by using an enzyme-linked immunosorbent assay. The biological function of sEGFR was analyzed in vitro using NSCLC cell lines, investigating effects on cell proliferation and migration. We found that plasma sEGFR was significantly decreased in the NSCLC patient group as compared to the control group (median value: 48.6 vs. 55.6 ng/mL respectively; p = 0.0002). Moreover, we demonstrated that sEGFR inhibits growth and migration of NSCLC cells in vitro through molecular mechanisms that included perturbation of EGF/EGFR cell signaling and holoreceptor internalization. These data show that sEGFR is a potential circulating biomarker with a physiological protective role, providing a first approach to the functional role of the soluble isoform of EGFR. However, the impact of these data on daily clinical practice needs to be further investigated in larger prospective studies.
机译：对于预后较差的疾病（例如非小细胞肺癌（NSCLC）），仍需要对生物学诊断因素进行评估，以提供临床相关信息以指导医师决策。表皮生长因子受体（EGFR）是非小细胞肺癌临床治疗中的一种有前途的分子。尽管在大型临床试验中广泛研究了EGFR跨膜形式，但很少考虑可能具有潜在临床用途的可溶性循环EGFR亚型（sEGFR）。这项研究调查了sEGFR作为NSCLC潜在的诊断生物标志物的用途，并表征了sEGFR的生物学功能，以阐明参与该蛋白作用过程的分子机制。使用酶联免疫吸附测定法分析了来自37名非晚期NSCLC患者和54名健康受试者的异质队列的血浆sEGFR水平。使用NSCLC细胞系在体外分析了sEGFR的生物学功能，研究了其对细胞增殖和迁移的影响。我们发现与对照组相比，NSCLC患者组的血浆sEGFR显着降低（中位数分别为48.6和55.6 ng / mL; p = 0.0002）。此外，我们证明了sEGFR通过分子机制（包括扰动EGF / EGFR细胞信号转导和整体受体内在化）抑制了NSCLC细胞的体外生长和迁移。这些数据表明，sEGFR是具有生理保护作用的潜在循环生物标志物，为EGFR可溶性同工型的功能作用提供了第一种方法。但是，这些数据对日常临床实践的影响需要在较大的前瞻性研究中进一步研究。

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