BACKGROUND Non-small cell lung cancer (NSCLC) is difficult to treat when metastasis has occurred. This study explores the use of cell-free DNA in the clinical management of NSCLC patients who have Kirsten rat sarcoma viral oncogene homolog (KRAS)-positive mutations and as a marker for prognosis. METHODS Peripheral blood collected from advanced NSCLC patients was examined with digital droplet polymerase chain reaction and ultraviolet spectrometry. KRAS mutations were analyzed and quantitated. The specificity and sensitivity of the proposed assay was computed by associating the results with tumor tissue specimens. Comparison against different sub-groups of patients with different metastatic sites and healthy volunteers were made. Patients were subsequently followed up and survival analysis was conducted. RESULTS Among the 186 patients recruited, 150 had concordant KRAS mutational profiles using cell-free DNA with tumor tissues. The assay sensitivity and specificity were 80.6% and 100%, respectively. For the 150 patients with concordant results, the range of cell-free DNA quantities in peripheral blood was 5.3 to 115 ng. Among the patient groups with different metastatic sites, we observed that patients with bone metastasis had higher concentrations of cell-free DNA. Survival analysis showed that these patients had worse survival outcome. Patients with higher KRAS counts in peripheral blood also had worse outcome. CONCLUSION The use of cell-free DNA presents opportunities for risk stratification of patients and possibly aids in the clinical management of the disease. In the current study for NSCLC, patients with bone metastases showed higher cell-free DNA concentrations. Quantitating the concentrations of cell-free DNA presents a noninvasive biomarker capable of prognostic utility.

中文翻译：

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使用游离 DNA 作为非小细胞肺癌骨转移患者的预后生物标志物。

背景技术当发生转移时，非小细胞肺癌(NSCLC)难以治疗。本研究探讨了无细胞 DNA 在具有 Kirsten 大鼠肉瘤病毒癌基因同源物 (KRAS) 阳性突变的 NSCLC 患者的临床管理中的用途，并作为预后标志物。方法 采用数字液滴聚合酶链反应和紫外分光光度计对晚期 NSCLC 患者采集的外周血进行检测。分析和定量 KRAS 突变。通过将结果与肿瘤组织样本相关联来计算所提出的测定的特异性和敏感性。对具有不同转移部位的患者和健康志愿者的不同亚组进行了比较。随后对患者进行随访并进行生存分析。结果 在招募的 186 名患者中，使用无细胞 DNA 和肿瘤组织，150 人具有一致的 KRAS 突变谱。检测灵敏度和特异性分别为 80.6% 和 100%。对于结果一致的 150 名患者，外周血中游离 DNA 量的范围为 5.3 至 115 ng。在具有不同转移部位的患者组中，我们观察到骨转移患者的游离 DNA 浓度较高。生存分析表明，这些患者的生存结果较差。外周血中 KRAS 计数较高的患者预后也较差。结论 无细胞 DNA 的使用为患者的风险分层提供了机会，并可能有助于疾病的临床管理。在目前针对 NSCLC 的研究中，骨转移患者的游离 DNA 浓度较高。