Divide and conquer: subproteomic approaches toward gastric cancer biomarker and drug target discovery

Abstract

The discovery of biomarkers for early detection and treatment for gastric cancer are two important gaps that proteomics have the potential to fill. Advancements in mass spectrometry, sample preparation and separation strategies are crucial to proteomics-based discoveries and subsequent translations from bench to bedside. A great number of studies exploiting various subproteomic approaches have emerged for higher-resolution analysis (compared with shotgun proteomics) that permit interrogation of different post-translational and subcellular compartmentalized forms of the same proteins as determinants of disease phenotypes. This is a unique and key strength of proteomics over genomics. In this review, the salient features, competitive edges and pitfalls of various subproteomic approaches are discussed. We also highlight valuable insights from several subproteomic studies that have increased our understanding of the molecular etiology of gastric cancer and the findings that led to the discovery of potential biomarkers/drug targets that were otherwise not revealed by conventional shotgun expression proteomics.

Keywords::

• biomarker
• drug target
• gastric cancer
• proteomics
• subproteomics

Acknowledgement

The authors thank M Hum and RA Jackson for proof reading the manuscript. This work is supported by the CBRG grant funded by the National Medical Research Council, Ministry of Health, Singapore.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Recent subproteomic approaches such as ‘alkylomics’ (e.g., the study of methylated and acetylated proteins) are promising, but are still in an infantile stage, where overcoming technical hurdles is required before they can become a popular tool like phosphoproteomics, which has already made a huge impact in molecular and translational cancer research.

• Sample preparation of clinical samples for subproteomics is a challenge. The development of methods to resolve cell-type heterogeneity and the purification of pure cell populations from tissues in sufficient quantities for proteomic analysis will be crucial.

• The use of systemic fluids (e.g., blood) for discovery and for the implementation of biomarkers for cancer detection with high specificity is not trivial, and it appears to be caused by the convergence of molecular events from various biological processes in the body. Cancer-specific biomarkers are highly valued.

• Translation from bench to bedside will remain impeded unless biomarker candidates have the chance to move out of the laboratory and into the clinic through proper infrastructure and funding that promotes clinical trials.

Notes