College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen, China.
Medical School of Chinese PLA & Medical Laboratory Center, First Medical Center of Chinese PLA General Hospital, Beijing, China.
Biomed Res Int. 2021 Feb 26;2021:5561569. doi: 10.1155/2021/5561569. eCollection 2021.
Lung cancer has a higher incidence rate and mortality rate than all other cancers. Early diagnosis and treatment of lung cancer remain a major challenge, and the 5-year survival rate of its patients is only 15%. Basic and clinical research, especially the discovery of biomarkers, is crucial for improving the diagnosis and treatment of lung cancer patients. To identify novel biomarkers for lung cancer, we used the iTRAQ8-plex labeling technology combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyze the serum and urine of patients with different stages of lung adenocarcinoma and healthy individuals. A total of 441 proteins were identified in the serum, and 1,161 proteins were identified in the urine. The levels of elongation factor 1-alpha 2, proteasome subunit alpha type, and spermatogenesis-associated protein increased significantly in the serum of patients with lung cancer compared with those in healthy controls. The levels of transmembrane protein 143, cadherin 5, fibronectin 1, and collectin-11 decreased significantly in the serum of patients with metastases compared with those of nonmetastatic lung cancer patients. In the urine of stage III and IV lung cancer patients, the prostate-specific antigen and prostatic acid phosphatase decreased significantly, whereas neutrophil defensin 1 increased significantly. The results of LC-MS/MS were confirmed by enzyme-linked immunosorbent assay (ELISA) for transmembrane protein 143, cadherin 5, fibronectin 1, and collectin-11 in the serum. These proteins may be a potential early diagnosis and metastasis biomarkers for lung adenocarcinoma. Furthermore, the relative content of these markers in the serum and urine could be used to determine the progression of lung adenocarcinoma and achieve accurate staging and diagnosis.
肺癌的发病率和死亡率均高于其他所有癌症。早期诊断和治疗肺癌仍然是一个主要挑战，其患者的 5 年生存率仅为 15%。基础和临床研究，特别是生物标志物的发现，对于改善肺癌患者的诊断和治疗至关重要。为了鉴定肺癌的新型生物标志物，我们使用 iTRAQ8-plex 标记技术联合液相色谱-串联质谱（LC-MS/MS）分析了不同分期肺腺癌患者和健康个体的血清和尿液。在血清中鉴定到 441 种蛋白质，在尿液中鉴定到 1161 种蛋白质。与健康对照组相比，肺癌患者血清中的延伸因子 1-α 2、蛋白酶体亚基 α 型和生精相关蛋白水平显著升高。跨膜蛋白 143、钙黏蛋白 5、纤连蛋白 1 和集蛋白 11 的水平在转移性肺癌患者的血清中显著降低，而非转移性肺癌患者的水平则显著降低。在 III 期和 IV 期肺癌患者的尿液中，前列腺特异性抗原和前列腺酸性磷酸酶显著降低，而中性粒细胞防御素 1 显著增加。LC-MS/MS 的结果通过酶联免疫吸附测定（ELISA）法在血清中对跨膜蛋白 143、钙黏蛋白 5、纤连蛋白 1 和集蛋白 11 进行了验证。这些蛋白质可能是肺腺癌早期诊断和转移的潜在生物标志物。此外，这些标志物在血清和尿液中的相对含量可用于确定肺腺癌的进展，实现准确分期和诊断。
