LC-MS/MS-Based Quantitative Proteomics Analysis of Different Stages of Non-Small-Cell Lung Cancer.

LC-MS/MS-Based Quantitative Proteomics Analysis of Different Stages of Non-Small-Cell Lung Cancer.
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基于 LC-MS/MS 的非小细胞肺癌不同阶段的定量蛋白质组学分析

DOI:
10.1155/2021/5561569
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发表时间:
2021
影响因子:
--
通讯作者:
Zhang Q
Zhang Q
中科院分区:
生物学3区
文献类型:
--
作者:
Zhou M;Kong Y;Wang X;Li W;Chen S;Wang L;Wang C;Zhang Q

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肺癌的发病率和死亡率高于所有其他癌症。肺癌的早期诊断和治疗仍然是一个重大挑战,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,对于提高肺癌患者的诊断和治疗至关重要。为了鉴定肺癌的新生物标志物,我们使用iTRAQ 8-plex标记技术结合液相色谱-串联质谱(LC-MS/MS)分析了不同阶段肺腺癌患者和健康个体的血清和尿液。在血清中共鉴定了441种蛋白质,在尿液中鉴定了1,161种蛋白质。肺癌患者血清中延伸因子1-α 2、蛋白酶体亚单位α型和精子发生相关蛋白水平显著高于健康对照组。与非转移性肺癌患者相比,转移性肺癌患者血清中跨膜蛋白143、钙粘蛋白5、纤维连接蛋白1和胶原聚集蛋白11的水平显著降低。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显著升高。通过酶联免疫吸附试验(ELISA)对血清中的跨膜蛋白143、钙粘蛋白5、纤连蛋白1和聚集蛋白-11进行LC-MS/MS的结果进行确认。这些蛋白可能是肺腺癌早期诊断和转移的潜在生物标志物。血清和尿液中这些标志物的相对含量可用于判断肺腺癌的进展情况,从而实现准确的分期和诊断。
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.
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