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

Abstract

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.

A Cell Differentiation Trajectory-Related Signature for Predicting the Prognosis of Lung Adenocarcinoma

“…Schulze et al have revealed that the MYC target V2 scores are associated with tumor aggressiveness and survival outcomes in ER-positive primary tumors, as well as in metastatic breast cancer [ 22 ]. Zhou et al found that the levels of spermatogenesis-associated protein increased significantly in the serum of patients with lung cancer compared with those in healthy controls [ 23 ]. The unfolded protein response is a prosurvival mechanism triggered by accumulation of unfolded or misfolded proteins in the endoplasmic reticulum, and unfolded protein response signalling plays important roles in cancer progression [ 24 ].…”

Anti-Metastatic Effect of Pyruvate Dehydrogenase Kinase 4 Inhibition in Bladder Cancer via the ERK, SRC, and JNK Pathways

“…Proteomic analysis is a great experimental tool for studying protein changes in cells, tissues, or organisms [ 17 ]. Recently, proteomic analysis has been widely used to enable the discovery of potential biomarkers and identification of tumor-related protein expression [ 18 , 19 , 20 ]. Because comparative phosphoproteome analysis can comprehensively quantify altered protein phosphorylation, it is effective to evaluate the intracellular effect of PDK4 as a kinase.…”

Proteomic and Phosphoproteomic Analyses Reveal the Oncogenic Role of PTK7-NDRG1 Axis in Non-small-cell Lung Cancer Cell Resistance to AZD9291

“…16 Proteomic approaches could be very helpful to identify resistance biomarkers representing the differences between sensitive and resistant cancer cells. 17 Comparative proteomics has successfully performed to identify many key target proteins involved in drug resistance, and several of these proteins have been verified as biomarkers in clinical cancer therapy. 18 Resistance biomarkers still have unmet clinical needs in both diagnosis and prognosis.…”

“…Proteome is dynamically changing in response to different environments, especially drug treatment . Proteomic approaches could be very helpful to identify resistance biomarkers representing the differences between sensitive and resistant cancer cells . Comparative proteomics has successfully performed to identify many key target proteins involved in drug resistance, and several of these proteins have been verified as biomarkers in clinical cancer therapy .…”