Department of Pulmonary Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100071, P.R. China.
National Center of Biomedical Analysis, Beijing 100069, P.R. China.
Mol Med Rep. 2020 Jan;21(1):51-60. doi: 10.3892/mmr.2019.10794. Epub 2019 Nov 5.
Matrix‑assisted laser desorption/ionization time‑of‑flight mass spectrometry (MALDI‑TOF‑MS) was employed to analyze differential serum and urine peptides in patients with small cell lung cancer (SCLC) and healthy individuals, and SCLC diagnostic classification models were constructed. Serum and urine samples from 72 patients with SCLC, age‑ and gender‑matched with 72 healthy individuals, were divided into training and testing sets in a 3:1 ratio. Serum and urine peptides were extracted using copper ion‑chelating nanomagnetic beads, and mass spectra were obtained using MALDI‑TOF‑MS. Peptide spectra for the training set were analyzed, and the classification model was constructed using ClinProTools (CPT). The testing set was used for blinded model validation. For training‑set sera, 122 differential peptide signal peaks with a mass of 0.8‑10 kDa were observed, and 19 peptides showed significantly different expression [P<0.0005; area under curve (AUC) ≥0.80]. CPT screened 5 peptide peaks (0.8114, 0.83425, 1.86655, 4.11133 and 5.81192 kDa) to construct the classification model. The testing set was used for the blinded validation, which had 95.0% sensitivity and 90.0% specificity. For the training‑set urine, 132 differential peptide signal peaks with m/z ratios of 0.8‑10 kDa were observed, and 8 peptides had significantly different expression (P<0.0005; AUC ≥0.80). Then, 5 peaks (1.0724, 2.37692, 2.7554, 4.75475 and 4.7949 kDa) were used for classification model construction. The testing set was used for 36 blinded validation, which had 85.0% sensitivity and 80.0% specificity. Among the differential peptides, 3 had the same significant peaks at 2.3764, 0.8778 and 0.8616 kDa, identified as fibrinogen α, glucose‑6‑phosphate isomerase and cyclin‑dependent kinase‑1, respectively. The present study highlighted the differences that exist in serum and urine peptides between patients with SCLC and healthy individuals. Serum and urine peptide diagnostic classification models could be constructed using MALDI‑TOF‑MS, and showed high sensitivity and specificity.
基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)用于分析小细胞肺癌(SCLC)患者和健康个体的差异血清和尿液肽,并构建 SCLC 诊断分类模型。将 72 例 SCLC 患者和 72 名年龄和性别匹配的健康个体的血清和尿液样本按 3:1 的比例分为训练集和测试集。使用铜离子螯合纳米磁珠提取血清和尿液肽,并用 MALDI-TOF-MS 获得质谱。分析训练集的肽谱,并使用 ClinProTools(CPT)构建分类模型。测试集用于盲模型验证。对于训练集血清,观察到质量为 0.8-10 kDa 的 122 个差异肽信号峰,其中 19 个肽表现出明显不同的表达[P<0.0005;曲线下面积(AUC)≥0.80]。CPT 筛选出 5 个肽峰(0.8114、0.83425、1.86655、4.11133 和 5.81192 kDa)来构建分类模型。使用测试集进行盲验证,其灵敏度为 95.0%,特异性为 90.0%。对于训练集尿液,观察到质量比为 0.8-10 kDa 的 132 个差异肽信号峰,其中 8 个肽表现出明显不同的表达(P<0.0005;AUC≥0.80)。然后,使用 5 个峰(1.0724、2.37692、2.7554、4.75475 和 4.7949 kDa)构建分类模型。使用 36 个测试集进行盲验证,其灵敏度为 85.0%,特异性为 80.0%。在差异肽中,有 3 个在 2.3764、0.8778 和 0.8616 kDa 处具有相同的显著峰,分别鉴定为纤维蛋白原α、葡萄糖-6-磷酸异构酶和细胞周期蛋白依赖性激酶-1。本研究强调了 SCLC 患者和健康个体血清和尿液肽之间存在的差异。使用 MALDI-TOF-MS 可以构建血清和尿液肽诊断分类模型,具有较高的灵敏度和特异性。