Identification of Serological Biomarkers for Early Diagnosis of Lung Cancer Using a Protein Array-Based Approach.
Identification of Serological Biomarkers for Early Diagnosis of Lung Cancer Using a Protein Array-Based Approach.
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DOI：
10.1074/mcp.ra117.000212
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发表时间：
2017-12
期刊：
影响因子：
--
通讯作者：
Huang Y
中科院分区：
文献类型：
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作者：
Pan J;Song G;Chen D;Li Y;Liu S;Hu S;Rosa C;Eichinger D;Pino I;Zhu H;Qian J;Huang Y
肺癌（LC）仍然是世界范围内恶性肿瘤死亡的主要原因。目前，缺乏用于LC早期诊断的血清学生物标志物是LC早期干预和预防的主要障碍。为了应对这一挑战，我们采用了两阶段策略，使用基于蛋白质阵列的方法来发现和验证生物标志物面板。在I期研究中，我们通过HuProt阵列获得了80例LC患者和20例健康受试者的血清学自身免疫图谱，并鉴定出170种与LC显著相关的候选蛋白。在II期研究中，我们构建了包含170个蛋白的LC聚焦阵列，并分析了一个大型队列，包括352名LC患者、93名健康个体和101名肺良性病变（LBL）患者。通过比较早期LC与健康和LBL联合组之间的自身免疫特征，我们确定并验证了p53、HRas和ETHE1的生物标志物组，其诊断早期LC的灵敏度为50%，特异性为>90%。最后，在ELISA试验中证实了该生物标志物面板的性能。总之，这项研究代表了最全面的蛋白质组调查之一，拥有最大的（即1101个独特样本）和最多样化的（即9个疾病组）队列，从而产生了具有良好性能的生物标志物面板。
Lung cancer (LC) remains the leading cause of mortality from malignant tumors worldwide. Currently, a lack of serological biomarkers for early LC diagnosis is a major roadblock for early intervention and prevention of LC. To undertake this challenge, we employed a two-phase strategy to discover and validate a biomarker panel using a protein array-based approach. In Phase I, we obtained serological autoimmune profiles of 80 LC patients and 20 healthy subjects on HuProt arrays, and identified 170 candidate proteins significantly associated with LC. In Phase II, we constructed a LC focused array with the 170 proteins, and profiled a large cohort, comprised of 352 LC patients, 93 healthy individuals, and 101 patients with lung benign lesions (LBL). The comparison of autoimmune profiles between the early stage LC and the combined group of healthy and LBL allowed us to identify and validate a biomarker panel of p53, HRas, and ETHE1 for diagnosis of early stage LC with 50% sensitivity at >90% specificity. Finally, the performance of this biomarker panel was confirmed in ELISA tests. In summary, this study represents one of the most comprehensive proteome-wide surveys with one of the largest (i.e. 1,101 unique samples) and most diverse (i.e. nine disease groups) cohorts, resulting in a biomarker panel with good performance.