Identification of serum proteome components associated with progression of non-small cell lung cancer.

Abstract

The aim of the present study was to perform comparative analysis of serum from patients with different stages of non-small cell lung cancer (NSCLC) using the three complementary proteomic approaches to identify proteome components associated with the progression of cancer. Serum samples were collected before any treatment from 200 patients with NSCLC, including 103 early stage, 64 locally advanced and 33 metastatic cancer samples, and from 200 donors without malignancy. The low-molecular-weight fraction of serum proteome was MALDI-profiled in all samples. Serum proteins were characterized using 2D-PAGE and LC-MS/MS approaches in a representative group of 30 donors. Several significant differences were detected between serum samples collected from patients with early stage cancer and patients with locally advanced cancer, as well as between patients with metastatic cancer and patients with local disease. Of note, serum components discriminating samples from early stage cancer and healthy persons were also detected. In general, about 70 differentiating serum proteins were identified, including inflammatory and acute phase proteins already reported to be associated with the progression of lung cancer (serum amyloid A or haptoglobin). Several differentiating proteins, including apolipoprotein H or apolipoprotein A1, were not previously associated with NSCLC. No significant differences in patterns of serum proteome components were detected between patients with adenocarcinoma and squamous cell carcinoma. In conclusion, we identified the biomarker candidates with potential importance for molecular proteomic staging of NSCLC. Additionally, several serum proteome components revealed their potential applicability in early detection of the lung cancer.

Clinical Application of Mass Spectrometry‐Based Proteomics in Lung Cancer Early Diagnosis

“…In addition, a few proteins at very high concentrations are present (primarily albumin, which alone represents more than half of the total protein content of plasma), which mask low abundance proteins that may be differentially regulated and potentially disease-relevant. Different strategies can be employed to overcome these challenges, including biochemically reducing the complexity of the plasma proteome, by depletion of the most abundant proteins (e.g., albumin and immunoglobulins [39,44,26,45,46,[52][53][54] ) and/or extensively fractionating proteins and peptides (see next paragraph). If interested in a specific class of proteins, for instance glycoproteins, specific enrichment methods can be used, [54] alone or in combination with depletion protocols.…”

“…Reflects progression of malignancy, including lung cancer. [ 76,78,39,45,47,20] Cytokeratin Component of intermediate filaments.…”

Construction of 2DE-Patterns of Plasma Proteins: Aspect of Potential Tumor Markers

“…and leukemia [105]. An elevated level of apo-H in serum samples from patients with early-stage NSCLC was reported [106]. Apo-H, α-1-acid glycoprotein 2 (ORM2), and complement C3 (C3) could be used for the discrimination between HCC patients and healthy people.…”

Bioinformatics Analysis of Apolipoprotein H Demonstrates Its Potential as a Prognostic Biomarker in Kidney Renal Clear Cell Carcinoma

“…APOH has been determined to correlate with hepatitis B virus (HBV) infection [11], systemic lupus erythematosus [12], and venous thrombosis [13]. Previous studies also suggested that APOH was related to the tumor development of non-small lung cancer [14], breast cancer [15], and acute myeloid leukaemia [16]. In terms of kidney-related disease, Norden et al have identi ed the over-excretion of APOH in urinary patients with several renal tubular diseases [17].…”