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Biomarkers in Colorectal Cancer
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Biomarkers in Colorectal Cancer

A special issue of Journal of Personalized Medicine (ISSN 2075-4426).

Deadline for manuscript submissions: closed (31 October 2018) | Viewed by 38051

Special Issue Editors

Prof. Dr. Enrico Mini

E-Mail Website
Guest Editor
Department of Health Sciences, Universita degli Studi di Firenze, Florence, Italy
Interests: gastrointestinal cancers; tumor drug resistance; biomarkers; pharmacogenetics; pharmacogenomics; translational studies
Special Issues, Collections and Topics in MDPI journals
Dr. Stefania Nobili

E-Mail Website
Guest Editor
Department of Neurosciences, Imaging and Clinical Sciences, "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy
Interests: tumor drug resistance; pharmacological strategies to overcome drug resistance; biomarkers; pharmacogenetics; pharmacogenomics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues

Colorectal cancer is the third cancer, both in terms of incidence and mortality in Western countries. Currently, molecular biomarkers play an important role in the detection and treatment of colorectal cancer patients. Molecular biomarkers are useful in recognizing colorectal cancer susceptibility or in the screening and diagnosis of early stages of the disease. The presence or absence of specific prognostic and predictive tumour biomarkers lead to a more rational selection of pharmacological treatments for colorectal cancer with consequent improvements in outcome. Molecular biomarkers predictive of drug toxicity are also available and help clinicians in the choice of the safest drug treatment for each patient. In this Special Issue, the current knowledge, as well as the future perspectives on the role of tumour biomarkers in colorectal cancer screening, diagnosis, treatment and follow-up, will be discussed.

Prof. Dr. Enrico Mini
Dr. Stefania Nobili
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Personalized Medicine is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • colorectal cancer
  • biomarkers
  • pharmacogenetics
  • pharmacogenomics
  • translational studies

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Published Papers (4 papers)

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Research

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11 pages, 590 KiB  
Article
DPYD, TYMS and MTHFR Genes Polymorphism Frequencies in a Series of Turkish Colorectal Cancer Patients
by Arsalan Amirfallah, Gizem Calibasi Kocal, Olcun Umit Unal, Hulya Ellidokuz, Ilhan Oztop and Yasemin Basbinar
J. Pers. Med. 2018, 8(4), 45; https://doi.org/10.3390/jpm8040045 - 13 Dec 2018
Cited by 21 | Viewed by 8299
Abstract
Fluoropyrimidine-based chemotherapy is extensively used for the treatment of solid cancers, including colorectal cancer. However, fluoropyrimidine-driven toxicities are a major problem in the management of the disease. The grade and type of the toxicities depend on demographic factors, but substantial inter-individual variation in [...] Read more.
Fluoropyrimidine-based chemotherapy is extensively used for the treatment of solid cancers, including colorectal cancer. However, fluoropyrimidine-driven toxicities are a major problem in the management of the disease. The grade and type of the toxicities depend on demographic factors, but substantial inter-individual variation in fluoropyrimidine-related toxicity is partly explained by genetic factors. The aim of this study was to investigate the effect of dihydropyrimidine dehydrogenase (DPYD), thymidylate synthase (TYMS), and methylenetetrahydrofolate reductase (MTHFR) polymorphisms in colorectal cancer patients. Eighty-five patients who were administered fluoropyrimidine-based treatment were included in the study. The DPYD, TYMS and MTHFR polymorphisms were scanned by a next generation Sequenom MassARRAY. Fluoropyrimidine toxicities were observed in 92% of all patients. The following polymorphisms were detected: DPYD 85T>C (29.4% heterozygote mutants, 7.1% homozygote mutants), DPYD IVS 14+1G>A (1.2% heterozygote mutants), TYMS 1494del TTAAAG (38.4% heterozygote mutants, 24.7% homozygote mutants), MTHFR 677C>T (43.5% heterozygote mutants, 9.4% homozygote mutants) and MTHFR 1298A>C (8.2% heterozygote mutants, 2.4% homozygote mutants). A statistically significant association was demonstrated between MTHFR 677C>T and fluoropyrimidine-related toxicity (p value = 0.007). Furthermore, MTHFR 1298A>C was associated with hematopoietic toxicity (p value = 0.008). MTHFR polymorphisms may be considered as related factors of fluoropyrimidine toxicity and may be useful as predictive biomarkers for the determination of the colorectal cancer patients who can receive the greatest benefit from fluoropyrimidine-based treatments. Full article
(This article belongs to the Special Issue Biomarkers in Colorectal Cancer)
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18 pages, 1885 KiB  
Article
Gene-Metabolite Interaction in the One Carbon Metabolism Pathway: Predictors of Colorectal Cancer in Multi-Ethnic Families
by S. Pamela K. Shiao, James Grayson and Chong Ho Yu
J. Pers. Med. 2018, 8(3), 26; https://doi.org/10.3390/jpm8030026 - 6 Aug 2018
Cited by 6 | Viewed by 6889
Abstract
For personalized healthcare, the purpose of this study was to examine the key genes and metabolites in the one-carbon metabolism (OCM) pathway and their interactions as predictors of colorectal cancer (CRC) in multi-ethnic families. In this proof-of-concept study, we included a total of [...] Read more.
For personalized healthcare, the purpose of this study was to examine the key genes and metabolites in the one-carbon metabolism (OCM) pathway and their interactions as predictors of colorectal cancer (CRC) in multi-ethnic families. In this proof-of-concept study, we included a total of 30 participants, 15 CRC cases and 15 matched family/friends representing major ethnic groups in southern California. Analytics based on supervised machine learning were applied, with the target variable being specified as cancer, including the ensemble method and generalized regression (GR) prediction. Elastic Net with Akaike’s Information Criterion with correction (AICc) and Leave-One-Out cross validation GR methods were used to validate the results for enhanced optimality, prediction, and reproducibility. The results revealed that despite some family members sharing genetic heritage, the CRC group had greater combined gene polymorphism-mutations than the family controls (p < 0.1) for five genes including MTHFR C677T, MTHFR A1298C, MTR A2756G, MTRR A66G, and DHFR 19bp. Blood metabolites including homocysteine (7 µmol/L), methyl-folate (40 nmol/L) with total gene mutations (≥4); age (51 years) and vegetable intake (2 cups), and interactions of gene mutations and methylmalonic acid (MMA) (400 nmol/L) were significant predictors (all p < 0.0001) using the AICc. The results were validated by a 3% misclassification rate, AICc of 26, and >99% area under the receiver operating characteristic curve. These results point to the important roles of blood metabolites as potential markers in the prevention of CRC. Future intervention studies can be designed to target the ways to mitigate the enzyme-metabolite deficiencies in the OCM pathway to prevent cancer. Full article
(This article belongs to the Special Issue Biomarkers in Colorectal Cancer)
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Review

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23 pages, 416 KiB  
Review
The Developing Story of Predictive Biomarkers in Colorectal Cancer
by Stergios Boussios, Mehmet Akif Ozturk, Michele Moschetta, Afroditi Karathanasi, Nikolaos Zakynthinakis-Kyriakou, Konstantinos H. Katsanos, Dimitrios K. Christodoulou and Nicholas Pavlidis
J. Pers. Med. 2019, 9(1), 12; https://doi.org/10.3390/jpm9010012 - 7 Feb 2019
Cited by 126 | Viewed by 13560
Abstract
Colorectal cancer (CRC) is the third most common malignancy worldwide. Surgery remains the most important treatment for non-metastatic CRC, and the administration of adjuvant chemotherapy depends mainly on the disease stage, which is still the strongest prognostic factor. A refined understanding of the [...] Read more.
Colorectal cancer (CRC) is the third most common malignancy worldwide. Surgery remains the most important treatment for non-metastatic CRC, and the administration of adjuvant chemotherapy depends mainly on the disease stage, which is still the strongest prognostic factor. A refined understanding of the genomics of CRC has recently been achieved thanks to the widespread use of next generation sequencing with potential future therapeutic implications. Microsatellite instability (MSI) has been suggested as a predictive marker for response to anti-programmed-cell-death protein 1 (PD-1) therapy in solid tumors, including CRC. It should be noted that not all cancers with MSI phenotype respond to anti-PD-1 immunotherapy, highlighting the urgent need for even better predictive biomarkers. Mitogen-Activated Protein Kinase (MAPK) pathway genes KRAS, NRAS, and BRAF represent important molecular targets and could serve as independent prognostic biomarkers in CRC, and identify those who potentially benefit from anti-epidermal growth factor receptor (EGFR) treatment. Emerging evidence has attributed a significant role to inflammatory markers including blood cell ratios in the prognosis and survival of CRC patients; these biomarkers can be easily assessed in routine blood exams and be used to identify high-risk patients or those more likely to benefit from chemotherapy, targeted therapies and potentially immunotherapy. Analysis of cell-free DNA (cfDNA), circulating tumor cells (CTC) and/or micro RNAs (miRNAs) could provide useful information for the early diagnosis of CRC, the identification of minimal residual disease and, the evaluation of the risk of recurrence in early CRC patients. Even the selection of patients suitable for the new targeted therapy is becoming possible with the use of predictive miRNA biomarkers. Finally, the development of treatment resistance with the emergence of chemo-resistance clones after treatment remains the most important challenge in the clinical practice. In this context it is crucial to identify potential biomarkers and therapeutic targets which could lead to development of new and more effective treatments. Full article
(This article belongs to the Special Issue Biomarkers in Colorectal Cancer)
13 pages, 810 KiB  
Review
The Emerging Role of Checkpoint Inhibition in Microsatellite Stable Colorectal Cancer
by David J. Hermel and Darren Sigal
J. Pers. Med. 2019, 9(1), 5; https://doi.org/10.3390/jpm9010005 - 16 Jan 2019
Cited by 28 | Viewed by 8167
Abstract
Checkpoint inhibitor therapy has introduced a revolution in contemporary anticancer therapy. It has led to dramatic improvements in patient outcomes and has spawned tremendous research into novel immunomodulatory agents and combination therapy that has changed the trajectory of cancer care. However, clinical benefit [...] Read more.
Checkpoint inhibitor therapy has introduced a revolution in contemporary anticancer therapy. It has led to dramatic improvements in patient outcomes and has spawned tremendous research into novel immunomodulatory agents and combination therapy that has changed the trajectory of cancer care. However, clinical benefit in patients with colorectal cancer has been generally limited to tumors with loss of mismatch repair function and those with specific germline mutations in the DNA polymerase gene. Unfortunately, tumors with these specific mutator phenotypes are in the minority. Recent pre-clinical and clinical studies have begun to reveal encouraging results suggesting that checkpoint inhibitor therapy can be expanded to an increasing number of colorectal tumors with microsatellite stability and the absence of traditional predictive biomarkers of checkpoint inhibitor response. These studies generally rely on combinations of checkpoint inhibitors with chemotherapy, molecular targeted therapy, radiation therapy, or other novel immunomodulatory agents. This article will review the most current data in microsatellite stable colorectal cancer. Full article
(This article belongs to the Special Issue Biomarkers in Colorectal Cancer)
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