Proteomics, genomics and transcriptomics: their emerging roles in the discovery and validation of colorectal cancer biomarkers

Abstract

Colorectal cancer (CRC) is the second most common cancer in females and the third in males. Since CRC is often diagnosed at an advanced stage when prognosis is poor, identification of biomarkers for early diagnosis is urgently required. Recent advances in proteomics, genomics and transcriptomics have facilitated high-throughput profiling of data generated from CRC-related genes and proteins, providing a window of information for biomarker discovery and validation. However, transfer of candidate biomarkers from bench to bedside remains a dilemma. In this review, we will discuss emerging proteomic technologies and highlight various sample types utilized for proteomics-based identification of CRC biomarkers. Moreover, recent breakthroughs in genomics and transcriptomics for the identification of CRC biomarkers, with particular emphasis on the merits of emerging methylomic and miRNAomic strategies, will be discussed. Integration of proteomics, genomics and transcriptomics will facilitate the discovery and validation of CRC biomarkers leading to the emergence of personalized medicine.

Keywords::

• colorectal cancer
• genomics
• methylomics
• miRNAomics
• proteomics
• transcriptomics

Financial & competing interests disclosure

EC Nice was supported, in part, by NHMRC Project Grant 603130, 1017078 and Development Grant 1017078. C Huang was supported by grants from the National 973 Basic Research Program of China (2013CB911300, 2012CB518900 and 2011CB910703), the National Science and Technology Major Project (2011ZX09302-001-01, 2012ZX09501001-003) and Chinese NSFC (81172173, 81225015). The authors have no other 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 apart from those disclosed. 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

• While the genome is static, the proteome is dynamic and constantly altering due to changes in the environment. Thus, while the human genome is now known to encode for only 20,300 proteins, the proteome consists of hundreds of thousands of protein isoforms due to splice variants and post-translational modifications (PTMs) including phosphorylation, glycosylation, ubiquitination, nitrosylation, methylation, acetylation, lipidation and proteolysis.

• PTMs help define biological function, which is frequently dysregulated in the disease process. Unraveling the specific roles of the PTMome in colorectal cancer (CRC) is essential for the understanding of CRC initiation and progression, and will ultimately reveal new biomarkers for the detection and surveillance of CRC.

• The development of improved sensitive and specific top-down protocols for the high-throughput analysis of protein isoforms will be essential for identifying novel, disease-specific biomarkers.

• Global deposition of raw data files in a common format to facilitate data mining is essential, and should be mandatory at publication. Key principals were developed around the Human Proteome Organization 2010 in Sydney, Australia, and policies to enforce this are currently being implemented by a number of the leading proteomic journals.

• The generation of validated ‘gold standards’ for quantitative studies is essential.

• Fully validated polyclonal and monoclonal antibodies are essential to complement mass spectrometry-based studies. This is being achieved through initiatives such as The Protein Atlas [162] and Antibodypedia [163].

Notes