1 Laboratory of Biochemistry (Oncobiology Unit), Biomedical Diagnostic Center (CDB).
2 Respiratory Institute.
Am J Respir Crit Care Med. 2016 Feb 15;193(4):427-37. doi: 10.1164/rccm.201404-0603OC.
We have previously identified six serum tumor markers (TMs) (carcinoembryonic antigen, carbohydrate antigen 15.3, squamous cell carcinoma-associated antigen, cytokeratin-19 fragment, neuron-specific enolase, and pro-gastrin-releasing peptide) related to the presence of lung cancer (LC).
To validate their individual performance in an independent cohort, and to explore if their combined assessment (≥1 abnormal TM value) is a more accurate marker for LC presence.
We determined these six TMs in 3,144 consecutive individuals referred to our institution by their primary care physician because of the clinical suspicion of LC.
LC was excluded in 1,316 individuals and confirmed in 1,828 patients (1,563 with non-small cell LC and 265 with small cell LC). This study validated the previously reported performance of each individual TM. We also showed that their combined assessment (≥1 abnormal TM) had a better sensitivity, specificity, negative predictive value, and positive predictive value (88.5, 82, 83.7, and 87.3%, respectively) than each TM considered individually and that it increased the diagnostic performance (area under the curve) of a clinical model that included tumor size, age, and smoking status. In patients with radiographic nodules less than 3 cm, the negative predictive value of the TM panel was 71.8%, hence providing some support for a more conservative diagnostic approach. Finally we identified two TMs (neuron-specific enolase and pro-gastrin-releasing peptide) that differentiate the risk of non-small cell LC from that of small cell LC.
The combined assessment of a panel of six serum TMs is a more accurate marker for LC presence than these same TMs considered individually. The potential of these TMs in the diagnostic and screening settings deserves further research.
我们之前已经确定了六个与肺癌（LC）存在相关的血清肿瘤标志物（TMs）（癌胚抗原、糖链抗原 15.3、鳞状细胞癌相关抗原、细胞角蛋白 19 片段、神经元特异性烯醇化酶和胃泌素释放肽前体）。
验证这些标志物在独立队列中的个体表现，并探讨其联合评估（≥1 个异常 TM 值）是否是 LC 存在的更准确标志物。
我们在因临床怀疑 LC 而由其初级保健医生转介到我们机构的 3144 例连续个体中确定了这六个 TMs。
在 1316 例个体中排除了 LC，并在 1828 例患者中证实了 LC（1563 例非小细胞 LC 和 265 例小细胞 LC）。本研究验证了每个单独 TM 先前报道的性能。我们还表明，它们的联合评估（≥1 个异常 TM）的敏感性、特异性、阴性预测值和阳性预测值（分别为 88.5%、82%、83.7%和 87.3%）优于每个单独考虑的 TM，并且它提高了包括肿瘤大小、年龄和吸烟状况在内的临床模型的诊断性能（曲线下面积）。在直径小于 3cm 的放射状结节患者中，TM 谱的阴性预测值为 71.8%，因此为更保守的诊断方法提供了一些支持。最后，我们确定了两个 TM（神经元特异性烯醇化酶和胃泌素释放肽前体）可区分非小细胞 LC 和小细胞 LC 的风险。
与单独考虑的这些 TM 相比，一组六种血清 TMs 的联合评估是 LC 存在的更准确标志物。这些 TM 在诊断和筛查中的潜力值得进一步研究。
