Abstract
Lung adenocarcinoma (LAC) progression is accompanied by changes in protein levels that may be reflected in body fluids, such as urine. Urine collected from LAC patients (n=34) and healthy controls (n=36) was analyzed via matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) combined with weak cationic exchange magnetic beads. The results revealed 76 urinary polypeptides significantly different between LAC patients and normal controls (P<0.05). Twenty-two of these peptides were up-regulated and 54 were down-regulated. Thirteen peptides had average peak intensities >600. Twelve of these 13 peptides were successfully identified using nano-liquid chromatography-tandem MS. Receiver operating characteristic analyses identified seven peptides with superior LAC diagnostic performances. Immunohistochemical staining in 20 paired LAC and adjacent normal tissues showed that IGKC, AAT, SH3BGRL3, osteopontin and gelsolin levels were higher in LAC tissues than in adjacent tissuesand were closely associated with LAC. Urinary peptides assessments may thus provide a novel, noninvasive, repeatable method for detecting and monitoring LAC. New, low-cost detection methods and bioinformatics tools are therefore urgently needed for the analysis of low abundance proteins and peptides in body fluids.
Highlights
Lung cancer is one of most commonly diagnosed cancers and the leading cause of cancer death worldwide [1]
Lung adenocarcinoma (LAC) progression is accompanied by changes in protein levels that may be reflected in body fluids, such as urine
Immunohistochemical staining in 20 paired LAC and adjacent normal tissues showed that Ig kappa chain C region (IGKC), AAT, SH3BGRL3, osteopontin and gelsolin levels were higher in LAC tissues than in adjacent tissuesand were closely associated with LAC
Summary
Lung cancer is one of most commonly diagnosed cancers and the leading cause of cancer death worldwide [1]. Lung cancer prognosis remains poor, and the 5-year survival rate of approximately 18% has not improved over several decades [1]. This is primarily due to late stage detection and a paucity of therapies effective against metastatic disease. Detection of lung cancer is hampered by several factors. Aggressive therapeutic intervention is hampered by a relatively high median patient age [3]. Lowdose spiral computed tomography (LDCT) is unsuitable for widespread screening due to high costs and false positive rates. No accurate and reliable lung cancer biomarkers have been identified to date
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