Biomarkers for Early Detection of Colitis-associated Colorectal Cancer - Current Concepts, Future Trends

: Colitis-associated colorectal cancer (CAC) remains a critical complication of ulcerative colitis (UC) with mortality of approximately 15%, which makes early CAC diagnosis crucial. The current standard of surveillance, with repetitive colonoscopies and histological testing of biopsied mucosa samples is burdensome and expensive, and therefore less invasive methods and reliable biomarkers are needed. Significant progress has been made thanks to continuous extensive research in this field, however no clinically relevant biomarker has been established so far. This review of the current literature presents the genetic and molecular differences between CAC and sporadic colorectal cancer and covers progress made in the early detection of CAC carcinogenesis. It focuses on biomarkers under development, which can be easily tested in samples of body fluids or breath and, once made clinically available, will help to differentiate between progressors (UC patients who will develop dysplasia) from non-progressors and enable early intervention to decrease the risk of cancer development.

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The Pivotal Player: Components of NF-κB Pathway as Promising Biomarkers in Colorectal Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms22147429 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7429

Author(s):

Matthew Martin ◽

Mengyao Sun ◽

Aishat Motolani ◽

Tao Lu

Keyword(s):

Colorectal Cancer ◽

Biological Response ◽

Significant Progress ◽

Therapeutic Approaches ◽

Successful Development ◽

Diagnostic Screening ◽

Proteomic Data ◽

Large Groups ◽

Made In

Over the last several decades, colorectal cancer (CRC) has been one of the most prevalent cancers. While significant progress has been made in both diagnostic screening and therapeutic approaches, a large knowledge gap still remains regarding the early identification and treatment of CRC. Specifically, identification of CRC biomarkers that can help with the creation of targeted therapies as well as increasing the ability for clinicians to predict the biological response of a patient to therapeutics, is of particular importance. This review provides an overview of CRC and its progression stages, as well as the basic types of CRC biomarkers. We then lay out the synopsis of signaling pathways related to CRC, and further highlight the pivotal and multifaceted role of nuclear factor (NF) κB signaling in CRC. Particularly, we bring forth knowledge regarding the tumor microenvironment (TME) in CRC, and its complex interaction with cancer cells. We also provide examples of NF-κB signaling-related CRC biomarkers, and ongoing efforts made at targeting NF-κB signaling in CRC treatment. We conclude and anticipate that with more emerging novel regulators of the NF-κB pathway being discovered, together with their in-depth characterization and the integration of large groups of genomic, transcriptomic and proteomic data, the day of successful development of more ideal NF-κB inhibitors is fast approaching.

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LEPR polymorphisms and haplotypes in Mexican patients with colorectal cancer

Biomédica ◽

10.7705/biomedica.v39i1.4091 ◽

2019 ◽

Vol 39 (1) ◽

pp. 205-211

Author(s):

Miriam Partida ◽

Melva Gutiérrez ◽

María De la Luz Ayala ◽

Nelly Margarita Macías ◽

Carlos Rogelio Alvizo ◽

...

Keyword(s):

Colorectal Cancer ◽

Linkage Disequilibrium ◽

Odds Ratio ◽

Gene Polymorphisms ◽

Cancer Development ◽

Sporadic Colorectal Cancer ◽

Heterozygous Genotype ◽

Increased Risk ◽

Haplotype Frequencies ◽

Hardy Weinberg Equilibrium

Introduction: Obesity and colorectal cancer could be linked by adipocytokines, which are proteins associated with cell proliferation. High levels of the adipocytokine leptin promote the development of colorectal cancer through its receptor.Objective: To determine the association between c.326A>G and c.668A>G LEPR gene polymorphisms and colorectal cancer.Materials and methods: DNA was extracted from the peripheral blood of 147 patients with sporadic colorectal cancer and 134 healthy people. Genotypes were obtained by PCRRFLP and the association was determined by the odds ratio (OR) test using the SPSS™, version 10.0, program. Haplotype frequencies and linkage disequilibrium were estimated by the Arlequin, version 3.5, software.Results: Both polymorphisms were in Hardy-Weinberg equilibrium. Only the c.326A>G heterozygous genotype revealed an increased risk for colorectal cancer development (OR=1.81, 95% CI=1.04-3.16, p=0.04). The AG haplotype showed a significant association with colorectal cancer (OR=0.58, 95% CI=0.35-0.96, p<0.03). Linkage disequilibrium between the variants was only evident for the patients group (r2=0.36). Conclusion: Our results suggest that AG individuals heterozygous for the c.326A>G LEPR variant have a higher risk of colorectal cancer development whereas the AG haplotype (c.326A/c.668G) has a protective effect in the Mexican population.

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The 116G > A MSH6 and IVS1-1121C > T PMS2 Genes Polymorphisms Modulate the Risk of the Sporadic Colorectal Cancer Development in Polish Population

Pathology & Oncology Research ◽

10.1007/s12253-017-0231-5 ◽

2017 ◽

Vol 24 (2) ◽

pp. 231-235 ◽

Cited By ~ 3

Author(s):

Piotr Zelga ◽

Karolina Przybyłowska-Sygut ◽

Marta Zelga ◽

Adam Dziki ◽

Ireneusz Majsterek

Keyword(s):

Colorectal Cancer ◽

Cancer Development ◽

Sporadic Colorectal Cancer ◽

Polish Population

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Sporadic Colorectal Cancer Development Shows Rejuvenescence Regarding Epithelial Proliferation and Apoptosis

PLoS ONE ◽

10.1371/journal.pone.0074140 ◽

2013 ◽

Vol 8 (10) ◽

pp. e74140 ◽

Cited By ~ 7

Author(s):

Katalin Leiszter ◽

Orsolya Galamb ◽

Ferenc Sipos ◽

Tibor Krenács ◽

Gábor Veres ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Development ◽

Sporadic Colorectal Cancer ◽

Epithelial Proliferation ◽

Proliferation And Apoptosis

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Molecular Biomarkers according to Primary Tumor Location in Colorectal Cancer: Current Standard and New Insights

Oncology ◽

10.1159/000510944 ◽

2020 ◽

pp. 1-9

Author(s):

Gianluigi De Renzi ◽

Giulio Gaballo ◽

Paola Gazzaniga ◽

Chiara Nicolazzo

Keyword(s):

Colorectal Cancer ◽

Distal Colon ◽

Biological Indicators ◽

Tumor Location ◽

Molecular Biomarkers ◽

Neoplastic Disease ◽

Current Standard ◽

Treatment Responses ◽

Colorectal Cancer Patients ◽

Made In

According to the 2018 GLOBOCAN database, colorectal cancer is one of the most common malignancies and leading causes of cancer-related death worldwide. During the last decades, considerable progress has been made in understanding the complex pathogenetic mechanisms involved in this neoplastic disease. Due to the need to improve treatment responses and clinical outcomes of colorectal cancer patients, the identification of new molecular biomarkers became a crucial spot in clinical oncology. As biological indicators of a specific pathological or physiological process, molecular markers play a central role in cancer detection, diagnosis, outcome prediction, and treatment choice. Considering the existing evidence that malignancies originating from distinct colonic regions behave differently, it is clear that specific biomarkers can be associated to right- or left-sided colon carcinomas, reflecting the distinct molecular signatures of these different tumor entities. The aim of this review is to summarize the main differences among tumors arising from proximal and distal colon in terms of current and emerging biomarkers.

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The risk of sporadic colorectal cancer development is not influenced by fat mass and obesity related gene polymorphism in Slavs

European Journal of Internal Medicine ◽

10.1016/j.ejim.2012.07.002 ◽

2012 ◽

Vol 23 (7) ◽

pp. e175-e176 ◽

Cited By ~ 3

Author(s):

Jaroslav A. Hubacek ◽

Dana Dlouha ◽

Martin Bobak ◽

Alena Jiraskova ◽

Libor Vitek

Keyword(s):

Colorectal Cancer ◽

Gene Polymorphism ◽

Fat Mass ◽

Cancer Development ◽

Sporadic Colorectal Cancer ◽

Related Gene

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Polymorphism of Gly39Glu (c.116G>A) hMSH6 is associated with sporadic colorectal cancer development in the Polish population: Preliminary results

Advances in Clinical and Experimental Medicine ◽

10.17219/acem/64877 ◽

2017 ◽

Vol 26 (9) ◽

pp. 1425-1429 ◽

Cited By ~ 1

Author(s):

Piotr Zelga ◽

Karolina Przybyłowska-Sygut ◽

Marta Zelga ◽

Adam Dziki ◽

Ireneusz Majsterek

Keyword(s):

Colorectal Cancer ◽

Cancer Development ◽

Sporadic Colorectal Cancer ◽

Polish Population ◽

Preliminary Results

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Performance comparison of the methylated BCAT1/IKZF1 ctDNA test (COLVERA) with the CEA assay for detection of recurrent colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.3589 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 3589-3589 ◽

Cited By ~ 1

Author(s):

Erin L. Symonds ◽

Susanne Kartin Pedersen ◽

David Murray ◽

Susan E Byrne ◽

Paul Hollington ◽

...

Keyword(s):

Colorectal Cancer ◽

Early Detection ◽

Blood Test ◽

Treatment Options ◽

Roc Curves ◽

Circulating Tumor Dna ◽

Performance Comparison ◽

Ct Scans ◽

Recurrent Colorectal Cancer ◽

Current Standard

3589 Background: Early detection of recurrent colorectal cancer (CRC) will improve treatment options, but the current standard blood test of carcinoembryonic-antigen (CEA) has suboptimal sensitivity for recurrence. This study compared performance of a quantitative circulating tumor DNA (ctDNA) assay for methylated BCAT1 and IKZF1 (COLVERA) with that of CEA. Methods: 301 patients were monitored for recurrence after clearance of primary CRC. Blood was collected at scheduled intervals and concentrations of CEA and ctDNA were measured using the LIAISON CEA test (Diasorin) and the COLVERA ctDNA test (Clinical Genomics). Surveillance for recurrent disease was examined using regular CT scans. Sensitivity of each blood test for recurrence was assessed in the sample collected closest to the time of imaging confirming recurrence status. Absence of recurrence was defined as at least two consecutive clear CT scans. Receiver operator characteristic (ROC) analyses were used to determine optimal positivity threshold for Colvera. Results: 131 patients underwent satisfactory assessment for recurrence and had blood testing performed within 12 months of determining recurrence status (61.8% male, mean age 62.6 ±.12.2(SD)y). Of the 47 recurrence cases, 37 (74%) were distant. The areas under the ROC curves were 0.7761 and 0.8188 for CEA and COLVERA, respectively (each p < 0.001). An optimal cut-off of 12.8pg/sample was determined for COLVERA and the standard 5ng/mL cut-off was selected for CEA. COLVERA had a significantly higher sensitivity for detecting recurrence as compared to CEA (68.1% vs 31.9%, p < 0.001) with a similar specificity (97.6% Vs 96.4%, p = 0.6547). A multivariate analysis determined COLVERA to be a predictor of recurrence independent of CEA with positive COLVERA samples being 66.4 times (95%CI 14.0-315.8) more likely to have recurrence confirmed within the study timeframe, whereas CEA was not a significant predictor of recurrence (p = 0.228). Conclusions: These findings indicate that COLVERA, reporting in quantitative mode, is a more sensitive test than CEA. It provides a viable alternative for sensitive and early detection of recurrent CRC. Clinical trial information: 12611000318987.

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Toward quantitative defect analysis using HREM

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100171304 ◽

1994 ◽

Vol 52 ◽

pp. 714-715

Author(s):

David J. Smith

Keyword(s):

Electron Microscope ◽

Unit Cell ◽

Defect Analysis ◽

Significant Progress ◽

Detailed Characterization ◽

Small Unit ◽

Resolution Electron ◽

High Resolution Electron Microscope ◽

Large Unit Cell ◽

Made In

The electron microscope has evolved to the level where it is now straightforward to record highresolution images from thin samples (t∼10 to 20nm) that are directly interpretable in terms of atomic arrangements. Whilst recorded images necessarily represent two-dimensional projections of the structure, many defects such as dislocations and interfaces may be linear or planar in nature and thus might be expected to be amenable to detailed characterization. In this review, we briefly consider the recent significant progress that has been made in quantitative defect analysis using the high-resolution electron microscope and then discuss some drawbacks to the technique as well as potential scope for further improvements. Surveys of defect modelling for some small-unit-cell materials and interfaces have recently been published, and reference should be made to other papers in this symposium for further examples.The technique of structure imaging originated in the early '70s with observations of large-unit-cell block oxides.

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