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Oliver, J. Omics Technologies and Colorectal Cancer. Encyclopedia. Available online: https://encyclopedia.pub/entry/19521 (accessed on 21 July 2024).
Oliver J. Omics Technologies and Colorectal Cancer. Encyclopedia. Available at: https://encyclopedia.pub/entry/19521. Accessed July 21, 2024.
Oliver, Jordi. "Omics Technologies and Colorectal Cancer" Encyclopedia, https://encyclopedia.pub/entry/19521 (accessed July 21, 2024).
Oliver, J. (2022, February 16). Omics Technologies and Colorectal Cancer. In Encyclopedia. https://encyclopedia.pub/entry/19521
Oliver, Jordi. "Omics Technologies and Colorectal Cancer." Encyclopedia. Web. 16 February, 2022.
Omics Technologies and Colorectal Cancer
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This entry is adapted from the peer-reviewed paper 10.3390/cancers14030817

Colorectal cancer (CRC) is one of the most frequent cancers worldwide. Early detection of CRC is crucial, as it greatly improves the survival of patients. Currently, the CRC screening programs consist of a stool test to detect the presence of blood in stool and a subsequent colonoscopy to confirm the diagnosis. However, CRC screening can be further improved with the use of new biomarkers. Omics technologies, that is, techniques that generate a vast amount of data, can help to establish these markers. 

omics colorectal cancer

1. Introduction

Colorectal cancer (CRC) is one of the most frequently diagnosed cancers, with more than 1.9 million estimated new cases worldwide [1]. In Spain, CRC accounted for around 15,288 deaths in 2018, and has an annual age-standardized mortality rate of 30 per 100,000 inhabitants. This makes CRC the sixth-leading cause of death and the second leading cause of cancer-related mortality [2]. Early diagnosis raises the 5-year survival rate of these patients up to 94% [3]. Given the high burden of CRC on the National Health Service and the importance of early detection, significant efforts have been directed toward developing CRC screening programs. The main aim of these programs is to remove pre-malignant lesions which could ultimately develop into malignant tumours, as well as to start treatment in early-stage detected cancers. This way, it is expected to reduce CRC incidence and CRC-specific mortality, which has been proven effective [4].
One of the main problems for CRC is the late diagnosis, giving rise to a decrease in survival since there is a lack of early biomarkers [5]. Different tools have been developed for CRC screening, which include colonoscopy, flexible sigmoidoscopy, guaiac faecal occult blood testing (gFOBT), faecal immunochemical testing (FIT), and carcinoembryonic antigen (CEA) in plasma, which has low sensitivity and specificity [6]. Intention-to-treat estimates from meta-analyses of large randomized trials report reductions in CRC mortality of 20–30% for flexible sigmoidoscopy [7][8], 8–16% for gFOBT, and 41% for FIT and follow-up colonoscopy [9]. Currently, the screening program in Spain consists of biennial FIT with colonoscopy follow-up on positive subjects, according to the European guidelines [10]. However, every autonomous region implements this program at a different pace and there are important differences among regions [11][12]. Although this screening program has led to a decrease in mortality, the performance of this test is suboptimal, with a sensitivity and specificity for CRC of 54–89% and 89–97%, respectively [13]. Furthermore, it has been noted that this sensitivity may vary with the tumour stage, being lower with early-stage CRC [14]. This leads to a substantial number of false negative and false positive tests and, consequently, to missed diagnoses or unneeded colonoscopies. Thus, there is an urgent need for more accurate and, ideally, non-invasive tests to implement for CRC screening and monitoring tumour progression and treatment efficacy.

2. Genomics

The National Cancer Institute defines genomics as the study of the complete set of DNA (including all of its genes) in a person or other organism. The genome contains all the information needed for an individual to develop and grow. Analyzing the genome may help researchers understand how genes interact with each other and the environment and how certain diseases, such as cancer, diabetes, or heart disease develop. This may lead to new ways to diagnose, treat, and prevent disease [15]. Genetic alterations have been identified as major players in tumourigenesis. Therefore, genomics has gained attention as a tool to identify genetic markers that can lead to better diagnosis and prognosis and at the same time, allow researchers to improve the understanding of cancer. Apart from gene mutations and single nucleotide polymorphisms (SNP), the epigenetic signature has also proven useful to establish a more personalised diagnosis [16].
The development of high-throughput methods for genome and gene expression studies has increased the amount of information available. These data are deposited in international public repositories and can be studied by other research groups. NCBI Gene Expression Omnibus (GEO) is the most important database repository of high-throughput gene expression data and hybridization arrays, chips, and microarrays [17]. The Cancer Genome Atlas (TCGA) of the National Cancer Institute (NCI) is another relevant database in oncology. TCGA is a project to classify the genetic mutations that cause cancer, using genome sequencing and integrating bioinformatics tools to analyse this information [18].
Finally, the use of metagenomics, which evaluates the microbiome genes, holds special promise for CRC. Metagenomics has shown the potential to identify differences between control and CRC-associated microbiomes and eventually describe new CRC biomarkers [19].

3. Transcriptomics

Transcriptomics is the study of all RNA molecules in a cell and could give more information about how genes are turned on and off in different cell types and how this can contribute to cancer [20]. Differential gene expression comparison studies have emerged as a prospective approach to detecting promising biomarkers of enormous clinical value. This type of study is fuelled by and analyses the data deposited in the TGCA and GEO databases [21].

4. Proteomics

Proteomics is the study of the structure and function of proteins, including how they work and interact with each other [22]. In the search for new CRC biomarkers, proteomics studies are focused on differential protein expression between normal and cancer cells or the detection of different proteomic profiles in corporal fluids. Some of the most useful techniques for the identification of protein biomarkers in cancer are two-dimensional gel electrophoresis coupled with liquid chromatography/mass spectrometry (2-DE-MS), two-dimensional difference gel electrophoresis (2D-DIGE), or liquid chromatography–mass spectrometry (LC-MS) [23]. Multiplexed quantitative proteomic assays are capable of measuring changes in proteins and their interacting partners, isoforms, and post-translational modifications [23].

5. Metabolomics

Metabolomics is the study of metabolites in cells and tissues, which can be measured in different body fluids. The presence of a tumour can alter the whole individual’s metabolism, and the use of some fuels can be modified to meet the energy demands of the tumour. Furthermore, the tumour metabolism may change as the tumour progresses. Considering that the dysregulation of metabolism is one of the hallmarks of cancer, this omics could open a new way to study cancer [24].

6. Glycomics

Glycomics studies the structure and function of glycans, N- and O- linked glycoproteins, glycolipids, and proteoglycans [25][26]. The most common alterations in lipid and protein glycosylation are an increase in the branching of N-glycans, high density of O-glycans, incomplete glycans synthesis, neosynthesis, and sialylation and fucosylation increase [27]. Glycans characterization can be done by a large number of techniques, such as microarrays, flow cytometry, enzyme-linked immunosorbent assay, mass spectrometry, and chromatographic techniques [27].

7. Volatolomics

Volatolomics is the study of volatile organic compounds that have high vapor pressure. This is a non-invasive, fast, and potentially inexpensive way of analysing the human body chemistry for monitoring of diseases such as cancer [28]. The volatilome, volatile organic compounds (VOC) profile, is being used in the detection of CRC. Alterations in the metabolism of cancer cells can be reflected in a characteristic profile of VOCs, as these compounds are produced in metabolic processes such as inflammation, cancer metabolic alterations, and necrosis processes [29][30][31][32][33]. Cancer-associated VOCs are directly excreted from the affected organ or tissue to stool or blood. Thus, the VOCs are exhaled in breath, excreted in urine, or released from the skin [34][35][36]. However, the VOCs interactions with the microbiota may affect the volatilome of stool [29]. The most used techniques in volatolomics are gas chromatography with mass spectrometry (GC–MS), which enables the separation and quantification of individual VOCs; proton transfer reaction—mass spectrometry (PTR-MS), for simultaneous real-time monitoring of VOCs without sample preparation; and eNose, which allows the analysis of a specific VOC pattern in real-time. The latter is a low cost, easy-to-use equipment that can detect cancer at an early stage and can differentiate between cancer and healthy subjects [29][33][37].
Several studies have demonstrated the potential of the exhaled volatilome for CRC diagnosis and screening due to its sensitivity and specificity. However, further studies and standardization of collection and analysis methods for volatilome detection and its application to CRC diagnosis are needed [31][35][36][37][38][39].

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Jordi Oliver
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