Abstract
Non-small cell lung cancer (NSCLC) is detected in all lung cancer patients and the serum samples as potential source are often used as a potential source for early diagnosis. In this study, we used the proteomic approaches combining 2-DE, 2-D DIGE and mass spectrometry to identify the potential serum biomarkers in NSCLC serum samples, and compare the result to normal serum samples. The haptoglobin alpha 2 subunit (HAP2) is one of the proteins we are interested in and showed the overexpression level in NSCLC serum amongst the NSCLC subtypes. The identity of HAP2 was confirmed by LC-MS/MS and NH2-terminal amino acid sequencing analyses, while the high expression level of HAP2 in NSCLC serum samples was validated using co-immunoprecipitation and western blotting. Interestingly, the high expression of HAP2 has specificity in human serum samples, but nonspecific expression in lung cancer tissues and is not observed in lung cancer cell lines except HepG2 hepatocellular carcinoma cell line. This indicates that HAP2 is not produced from lung tissues and/or cells, but may be secreted from the liver. In addition, HAP2 isoforms and its post-translational modifications (PTMs) could be detected by various staining methods such as phosphoprotein, glycoprotein stains and FITC-labeled lectins stain. The different carbohydrate specificities of HAP2 isoforms in NSCLC serum samples, especially sialyl Lewis x, was observed and may correlate to the development or metastasis of lung cancer. We suggest that HAP2 may become a potentially useful serum biomarker for early diagnostic and therapeutic applications.
Highlights
Lung cancer is the cause of more cancer-related mortality in the world today for both men and women than any other cancer
Our result suggested that the expression of sialyl Lewis x carbohydrate antigen in non-small cell lung cancer (NSCLC) serum sample might cause a change in the glycosylation of haptoglobin alpha 2 subunit (HAP2) protein in NSCLC serum
We reported the proteomic analysis of potential protein markers in NSCLC lung cancer serum using gel-based proteomic tools, including 2-DE, 2-D DIGE and MS
Summary
Lung cancer is the cause of more cancer-related mortality in the world today for both men and women than any other cancer. Over the past two decades, significant progress has been made toward understanding the molecular pathogenesis of human lung cancer by the identification and characterization of various cancer-related genes and/or proteins that are genetically or epigenetically altered in human lung cancer. Numerous protein markers have been elucidated in human serum, urine, seminal fluid and histological specimens that exhibit varying capacities to detect lung cancer and predict disease cause. The Haptoglobin alpha-2 subunit (HAP2), which is the up-regulated protein in NSCLC serum, is our target protein and is used to validate the expression level in various human materials for answering the question of HAP2 production from lung cancer tissues and/or cells. We initiated the present work to elucidate the potential biomarkers in NSCLC serum, especially HAP2, the characterization of PTMs by HAP2, and the source of HAP2
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