Differentially expressed glycosylated patterns of α-1-antitrypsin as serum biomarkers for the diagnosis of lung cancer

Abstract

Lung cancer is the most common malignancy worldwide. Thus, there is a critical need for diagnostic biomarkers with adequate sensitivity and specificity for lung cancer detection. Glycans in glycoproteins are significantly altered in cancer, and may serve as a tool for identifying potential diagnostic biomarkers. Recent studies have reported changes in α-1-antitrypsin (A1AT) glycosylation in lung cancer serum, tissue and cell lines. In this study, a lectin microarray was used to detect glycosylation changes in serum A1AT from patients with lung adenocarcinoma (ADC), squamous cell lung cancer, small-cell lung cancer (SCLC) and benign pulmonary diseases. Differentially expressed glycosylated patterns of A1AT were identified by lectin arrays and were confirmed by lectin-based enzyme-linked immunosorbent assay (ELISA). We found that galactosylated A1AT could distinguish non-small-cell lung cancer (NSCLC) from benign pulmonary diseases (AUC = 0.834); fucosylated A1AT showed exceptional capability in distinguishing ADC from benign diseases (AUC = 0.919) or other lung cancer subtypes (AUC = 0.844), and A1AT containing poly-LacNAc could detect SCLC from benign diseases (AUC = 0.905) or NSCLC (AUC = 0.707). The present study indicates that glycosylated patterns of A1AT may serve as potential biomarkers for detection of lung cancer. Further studies in larger sample sizes are necessary to validate the clinical utility of these markers.

Comparison of the glycopattern alterations of mitochondrial proteins in cerebral cortex between rat Alzheimer’s disease and the cerebral ischemia model

“…In neurodegenerative diseases, mitochondrial dysfunction has been reported to occur early and to act causally in disease pathogenesis57. Furthermore, in multiple diseases, the glycopattern of proteins is different to that in normal samples394058, and the differentially expressed glycans may play an important role in the pathological process. Many studies have focused on the mitochondrial proteome to explore the pathogenesis of AD46 and ischemic stroke47; however, there has been little focus on the glycopattern of the mitochondrial glycoproteins in these two diseases.…”

“…Glycosylation is one of the most common and frequent post-translational protein modifications, which occurs in approximately half of proteins3839. There are two major types of protein glycosylation, including N -glycosylation of the asparagine side-chains and O -glycosylation of the serine or threonine side-chains40.…”

“…Abnormal glycan structures, such as incomplete synthesis or neo-synthesis, are frequently associated with disease onset and progression394245. In the past few years, scientific interest in the abnormal expression of the mitochondrial proteome has increased not only for AD46 but also for ischemic brain injury47.…”

Glycopatterns of Urinary Protein as New Potential Diagnosis Indicators for Diabetic Nephropathy

“…Alterations of sialylated MUC1 glycosylation detected by lectin microarray could be indispensable for the development of cholangiocarcinoma [15]. Glycosylated patterns of A1AT (alpha-1-antitrypsin) may serve as potential biomarkers for early detection [16]. For DN, nonenzymatic glycosylation product such as glycated albumin was strongly associated with incident diabetes and its microvascular complications.…”

Sweets for a Bitter End: Lung Cancer Cell–Surface Protein Glycosylation Mediates Metastatic Colonization

“…Tumors cells of various origins show overall increases in sialic sugars on membrane glycoproteins and glycolipids (1). Interestingly, progression of the most frequent subtype of lung cancer, lung adenocarcinoma (LUAD), has been associated with increased levels of glycosylated protein in patient sera (2). Despite its clinical relevance, the biological and mechanistic implication of this observation is poorly understood.…”