Application of glycoproteomics for the discovery of biomarkers in lung cancer

Abstract

Lung cancer is the leading cause of cancer-related deaths in the United States. Approximately 40-60% of lung cancer patients present with locally advanced or metastatic disease at the time of diagnosis. Lung cancer development and progression are a multistep process that is characterized by abnormal gene and protein expressions ultimately leading to phenotypic change. Glycoproteins have long been recognized to play fundamental roles in many physiological and pathological processes, particularly in cancer genesis and progression. In order to improve the survival rate of lung cancer patients, the discovery of early diagnostic and prognostic biomarkers is urgently needed. Herein, we reviewed the recent technological developments of glycoproteomics and published data in the field of glycoprotein biomarkers in lung cancer, and discussed their utility and limitations for the discovery of potential biomarkers in lung cancer. Although numerous papers have already acknowledged the importance of the discovery of cancer biomarkers, the systemic study of glycoproteins in lung cancer using glycoproteomic approaches is still suboptimal. Recent development in the glycoproteomics will provide new platforms for identification of potential protein biomarkers in lung cancers.

Figure 1

The workflow of glycoprotein-based and glycopeptides-based analyses. Briefly, in the glycoprotein-based approach, glycoproteins are enriched first, then digested into peptides and analyzed by mass spectrometry (MS). In the glycopeptide-based approach, proteins are digested enzymatically and/or chemically; then, the peptide mixture is enriched for glycopeptides and identified by MS analysis. SPEG: solid-phase extraction of N-linked glycopeptides).

Figure 2

Histomorphology of normal lung parenchyma, squamous cell carcinoma and adenocarcinoma.