Glycoproteomics using fluid-based specimens in the discovery of lung cancer protein biomarkers: Promise and challenge
ABSTRACT Lung cancer is the number one cancer in the US and worldwide. In spite of the rapid progression in personalized treatments, the overall survival rate of lung cancer patients is still suboptimal. Over the past decade, tremendous efforts have been focused on the discovery of protein biomarkers to facilitate the early detection and monitoring lung cancer progression during treatment. In addition to tumor tissues and cancer cell lines, a variety of biological material has been studied. Particularly in recent years, studies using fluid-based specimen or so-called "fluid-biopsy" specimen have progressed rapidly. Fluid specimens are relatively easier to collect than tumor tissue, and they can be repeatedly sampled during the disease progression. Glycoproteins have long been recognized to play fundamental roles in many physiological and pathological processes. In this review, we focus the discussion on recent advances of glycoproteomics, particularly in the identification of potential protein biomarkers using so-called fluid-based specimens in lung cancer. The purpose of this review is to summarize current strategies, achievements and perspectives in the field. This insight will highlight the discovery of tumor-associated glycoprotein biomarkers in lung cancer and their potential clinical applications.
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ABSTRACT: Lung cancer is the number one cause of cancer-related deaths in the United States and worldwide. The complex protein changes and/or signature of protein expression in lung cancer, particularly in non-small cell lung cancer (NSCLC) has not been well defined. Although several studies have investigated the protein profile in lung cancers, the knowledge is far from complete. Among early studies, mucin5B (MUC5B) has been suggested to play an important role in the tumor progression. MUC5B is the major gel-forming mucin in the airway. In this study, we investigated the overall protein profile and MUC5B expression in lung adenocarcinomas, the most common type of NSCLCs. Lung adenocarcinoma tissue in formalin-fixed paraffin-embedded (FFPE) blocks was collected and microdissected. Peptides from 8 tumors and 8 tumor-matched normal lung tissue were extracted and labeled with 8-channel iTRAQ reagents. The labeled peptides were identified and quantified by LC-MS/MS using an LTQ Orbitrap Velos mass spectrometer. MUC5B expression identified by iTRAQ labeling was further validated using immunohistochemistry (IHC) on tumor tissue microarray (TMA). A total of 1288 peptides from 210 proteins were identified and quantified in tumor tissues. Twenty-two proteins showed a greater than 1.5-fold differences between tumor and tumor-matched normal lung tissues. Fifteen proteins, including MUC5B, showed significant changes in tumor tissues. The aberrant expression of MUC5B was further identified in 71.1% of lung adenocarcinomas in the TMA.Discussions: A subset of tumor-associated proteins was differentially expressed in lung adenocarcinomas. The differential expression of MUC5B in lung adenocarcinomas suggests its role as a potential biomarker in the detection of adenocarcinomas.Clinical Proteomics 11/2013; 10(1):15. DOI:10.1186/1559-0275-10-15
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ABSTRACT: Respiratory diseases are highly prevalent and affect humankind worldwide causing extensive morbidity and mortality with the environment playing an important role. Given the complex structure of the airways sophisticated tools are required for early diagnosis; initial symptoms are non-specificand the clinical diagnosis is made frequently late.Over the last few years, proteomics has made a high technological progress in mass spectrometry-based protein identification, and has allowed gaining new insides into disease mechanisms and identifying potential novel therapeutic targets. This review will highlight the contributions of proteomics towards the understanding of the respiratory proteome listing potential biomarkers, and its potential application to the clinic. We also outline the contributions of proteomics to creating a personalized approach in respiratory medicine.Journal of Proteome Research 11/2014; 14(1). DOI:10.1021/pr500935s · 5.00 Impact Factor
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ABSTRACT: Background SALL4 and OCT4 are transcription factors and play essential roles in stem cell development and oncogenesis. However, the expression of these transcription factors has not been well studied in lung cancers. In this study, we evaluated the expression of SALL4 and OCT4 in non-small cell lung carcinomas (NSCLC) by immunochemistry. NSCLC tissue microarrays (TMAs) were constructed with a total of 77 primary lung adenocarcinomas (ADCs) and 90 primary lung squamous cell carcinomas (SqCCs). A mouse monoclonal anti-human SALL4 (1:400 dilution) and a polyclonal anti-human OCT4 (1:200 dilution) antibodies were used. Nuclear staining of SALL4 and OCT4 was scored semi-quantitatively using a three tiered scale. The expressions of SALL4 and OCT4 were correlated with the tumor differentiation, pathological stage, and patients’ clinical information. Results In primary ADCs, the stronger expression of SALL4 and OCT4 was 7.8% and 9.1%, respectively. The stronger expression of SALL4 was inversely correlated with tumor differentiations. In primary SqCCs, the stronger expressions of SALL4 and OCT4 were 16.7% and 0%, respectively. The expression of SALL4 is correlated with the expression of OCT4, but inversely correlated with the tumor stage in SqCCs. Conclusions We found that both SALL4 and OCT4 were differentially expressed in a subset of primary ADC and SqCC. Our finding suggest that different stem cell markers may be expressed and/or play differential role in different subtypes of NSCLC. The potential role of SALL4 and OCT4 needs to be further investigated in NSCLC.12/2014; 2(1):10. DOI:10.1186/s40247-014-0010-7