Promising Epigenetic Biomarkers for the Early Detection of Colorectal Cancer: A Systematic Review.
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ABSTRACT:
SUBMITTER: Anghel SA
PROVIDER: S-EPMC8508438 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Colorectal cancer (CRC) ranks as the third most prevalent cancer worldwide. Early detection of this neoplasia has proven to improve prognosis, resulting in a 90% increase in survival. However, available CRC screening methods have limitations, requiring the development of new tools. MicroRNA biomarkers have emerged as a powerful screening tool, as they are highly expressed in CRC patients and easily detectable in several biological samples. While microRNAs are extensively studied in blood samples, recent interest has now arisen in other samples, such as stool samples, where they can be combined with existing screening methods. Among the microRNAs described in the literature, microRNA-21-5p and microRNA-92a-3p and their cluster have demonstrated high potential for early CRC screening. Furthermore, the combination of multiple microRNAs has shown improved performance in CRC detection compared to individual microRNAs. This review aims to assess the available data in the literature on microRNAs as promising biomarkers for early CRC screening, explore their advantages and disadvantages, and discuss the optimal study characteristics for analyzing these biomarkers.
| S-EPMC10341417 | biostudies-literature
Project description:BACKGROUND:The sensitive detection of recurrent colorectal cancer (CRC) by the measurement of circulating tumor DNA (ctDNA) might improve the chance of a cure. This study compared a quantitative methylated ctDNA test with carcinoembryonic antigen (CEA) in the setting of surveillance for recurrence. METHODS:Blood samples collected either during surveillance or within 12 months of the confirmation of recurrence were assayed for ctDNA (methylated branched-chain amino acid transaminase 1 [BCAT1]/Ikaros family zinc-finger 1 protein [IKZF1]) and CEA. The optimal ctDNA threshold was determined by receiver operating characteristic analysis, and the test performance for the detection of recurrence was compared with CEA (5 ng/mL threshold). RESULTS:The study cohort comprised 144 eligible patients and included 50 recurrence events. The sensitivity of the methylated ctDNA test for recurrence was 66.0% (95% confidence interval [CI], 57.1%-69.3%), which was significantly higher than the sensitivity of CEA (31.9%; 95% CI, 22.8%-36.6%; P < .001). The sensitivity for resectable recurrence (n = 20) was also higher (ctDNA, 60.0%; CEA, 20.0%; P = .01). The specificity did not differ between the tests (ctDNA, 97.9%; 95% CI, 93.2%-99.6%; CEA, 96.4%; 95% CI, 91.4%-99.0%). When adjustments were made for other predictors of the presence of recurrence, a positive ctDNA test was an independent predictor (odds ratio, 155.7; 95% CI, 17.9-1360.6; P < .001), whereas CEA was not (odds ratio, 2.5; 95% CI, 0.3-20.6; P = .407). CONCLUSIONS:The quantitative ctDNA test showed superior sensitivity in comparison with CEA without a difference in the specificity for detecting recurrent CRC. Longitudinal studies are warranted to further assess the utility (specifically the survival benefit) of methylated BCAT1/IKZF1 ctDNA in the surveillance of patients with CRC.
| S-EPMC7155014 | biostudies-literature
Project description:BackgroundSeveral approaches have been suggested to be useful in the early detection of colorectal neoplasms. Since metabolites are closely related to the phenotype and are available from different human bio-fluids, metabolomics are candidates for non-invasive early detection of colorectal neoplasms.ObjectivesWe aimed to summarize current knowledge on performance characteristics of metabolomics biomarkers that are potentially applicable in a screening setting for the early detection of colorectal neoplasms.DesignWe conducted a systematic literature search in PubMed and Web of Science and searched for biomarkers for the early detection of colorectal neoplasms in easy-to-collect human bio-fluids. Information on study design and performance characteristics for diagnostic accuracy was extracted.ResultsFinally, we included 41 studies in our analysis investigating biomarkers in different bio-fluids (blood, urine, and feces). Although single metabolites mostly had limited ability to distinguish people with and without colorectal neoplasms, promising results were reported for metabolite panels, especially amino acid panels in blood samples, as well as nucleosides in urine samples in several studies. However, validation of the results is limited.ConclusionsPanels of metabolites consisting of amino acids in blood and nucleosides in urinary samples might be useful biomarkers for early detection of advanced colorectal neoplasms. However, to make metabolomic biomarkers clinically applicable, future research in larger studies and external validation of the results is required.
| S-EPMC6116151 | biostudies-literature
Project description:ObjectivesBlood-based proteins might be an attractive option for early detection of colorectal cancer (CRC), but individually they are unlikely to achieve the diagnostic performance required for population based screening. We aimed at summarizing current evidence of diagnostic performance of signatures based on multiple proteins for early detection of CRC.MethodsA systematic literature review adhering to the PRISMA (preferred reporting items for systematic reviews and meta-analysis) guidelines was performed. PubMed and Web of Science databases were searched for potentially relevant studies published until 28th August, 2017. Relevant studies were identified by predefined eligibility criteria. Estimates of indicators of diagnostic performance such as sensitivity, specificity, and the area under the curve (AUC), along with information on validation and other key methodological procedures were extracted. Study quality was assessed by a QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) instrument tool.ResultsThirty six eligible studies with numbers of CRC cases ranging from 23 to 512 and the number of proteins included in signatures ranged from 3 to 13 were identified. Reported Youden's Index and AUC ranged from 0.19 to 0.95 and from 0.62 to 0.996, respectively. However most studies, especially those reporting better diagnostic performance, were conducted in clinical rather than screening setting and many studies lacked any internal or external validation of identified algorithm.ConclusionsBlood-based tests using signatures of multiple proteins may be a promising approach for non-invasive CRC screening. However, promising signatures identified in clinical settings still require rigorous evaluation in large studies conducted in true screening setting.
| S-EPMC5717517 | biostudies-literature
Project description:Colorectal cancer (CRC) represents the third-most common cancer worldwide and one of the main challenges for public health. Despite great strides in the application of neoadjuvant and adjuvant therapies for rectal and colon cancer patients, each of these treatments is still associated with certain adverse effects and different response rates. Thus, there is an urgent need for identifying novel potential biomarkers that might guide personalized treatments for specific subgroups of patients. However, until now, there are no biomarkers to predict the manifestation of adverse effects and the response to treatment in CRC patients. Herein, we provide a systematic review of epidemiological studies investigating epigenetic biomarkers in CRC patients receiving neoadjuvant or adjuvant therapy, and their potential role for the prediction of outcomes and response to treatment. With this aim in mind, we identified several epigenetic markers in CRC patients who received surgery with adjuvant or neoadjuvant therapy. However, none of them currently has the robustness to be translated into the clinical setting. Thus, more efforts and further large-size prospective studies and/or trials should be encouraged to develop epigenetic biomarker panels for personalized prevention and medicine in CRC cancer.
| S-EPMC6696286 | biostudies-literature
Project description:The development and use of predictive biomarkers to guide treatment decisions are paramount not only for improving survival in patients with metastatic colorectal cancer (mCRC), but also for sparing them from unnecessary toxicity and reducing the economic burden of expensive treatments. We conducted a systematic review of published studies and evaluated the predictive biomarker landscape in the mCRC setting from a molecular and clinical viewpoint. Studies analyzing predictive biomarkers for approved therapies in patients with mCRC were identified systematically using electronic databases. Preclinical studies and those providing no relevant information were excluded. A total of 173 studies comprising 148 biomarkers were selected for final analysis. Of all the biomarkers analyzed, 1.4% (two of 148) were explored in a prospective manner, whereas 98.6% (146 of 148) were evaluated in retrospective studies. Of the latter group, 78.8% (115 of 146) were not tested in subsequent phases, 9.6% (14 of 146) were tested in other retrospective cohorts, 8.9% (13 of 146) were retrospectively tested in at least one or more randomized cohorts, and only 2.7% (four of 146) were prospectively tested in a clinical trial. Finally, only 1.4% (two of 148) were validated sufficiently and are recognized as biomarkers for guiding treatment decision making in patients with mCRC. These markers were RAS mutational status for anti-EGFR antibodies and microsatellite instability status for anti-programmed cell death-1 drugs. Despite notable efforts to identify predictive biomarkers for various therapies used in the mCRC setting, because of a lack of data beyond retrospective studies and successful biomarker-driven approaches, only two molecular biomarkers have thus far found their translation into the clinic, highlighting the imperative need for implementing novel strategies and additional research in this clinically important field.
| S-EPMC7446314 | biostudies-literature
Project description:Colorectal cancer (CRC) is one of the most common cancers and a leading cause of cancer-related deaths worldwide. Despite numerous advances in therapeutic approaches, this cancer has a poor prognosis when it is diagnosed at late stages. Therefore, the scientific effort is nowadays directed towards the development of new non-invasive and dynamic biomarkers to improve the survival expectancy of CRC patients. In this sense, deregulated expression of many miRNAs has been shown to play an important role for CRC carcinogenesis and dissemination. Noticeably, an increasing number of studies highlight that circulating miRNAs, including those traveling inside exosomes or those released by tumor cells into circulation, constitute a promising tool for early detection, prognosis and therapy selection of CRC. Therefore, in this review we focus on the clinical potential of blood circulating miRNAs as emerging biomarkers with high value to improve the clinical management of CRC patients, providing a deep and complete perspective of the realities and challenges to translate these biomarkers to the clinical context.
| S-EPMC6679000 | biostudies-literature
Project description:Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide. One of the fundamental processes driving the initiation and progression of CRC is the accumulation of a variety of genetic and epigenetic changes in colonic epithelial cells. Over the past decade, major advances have been made in our understanding of cancer epigenetics, particularly regarding aberrant DNA methylation, microRNA (miRNA) and noncoding RNA deregulation, and alterations in histone modification states. Assessment of the colon cancer "epigenome" has revealed that virtually all CRCs have aberrantly methylated genes and altered miRNA expression. The average CRC methylome has hundreds to thousands of abnormally methylated genes and dozens of altered miRNAs. As with gene mutations in the cancer genome, a subset of these epigenetic alterations, called driver events, are presumed to have a functional role in CRC. In addition, the advances in our understanding of epigenetic alterations in CRC have led to these alterations being developed as clinical biomarkers for diagnostic, prognostic, and therapeutic applications. Progress in this field suggests that these epigenetic alterations will be commonly used in the near future to direct the prevention and treatment of CRC.
| S-EPMC4589488 | biostudies-literature
Project description:Circulating microRNAs (miRNA) are emerging as promising diagnostic biomarkers for colorectal cancer, but their usefulness for detecting early colorectal neoplasms remains unclear. This study aimed to identify serum miRNA biomarkers for the identification of patients with early colorectal neoplasms.A cohort of 237 serum samples from 160 patients with early colorectal neoplasms (148 precancerous lesions and 12 cancers) and 77 healthy subjects was analyzed in a three-step approach that included a comprehensive literature review for published biomarkers, a screening phase, and a validation phase. RNA was extracted from sera, and levels of miRNAs were examined by real-time RT-PCR.Nine miRNAs (miR-18a, miR-19a, miR-19b, miR-20a, miR-21, miR-24, miR-29a, miR-92, and miR-125b) were selected as candidate biomarkers for initial analysis. In the screening phase, serum levels of miR-21, miR-29a, and miR-125b were significantly higher in patients with early colorectal neoplasm than in healthy controls. Elevated levels of miR-21, miR-29a, and miR-125b were confirmed in the validation phase using an independent set of subjects. Area under the curve (AUC) values for serum miR-21, miR-29a, miR-125b, and their combined score in discriminating patients with early colorectal neoplasm from healthy controls were 0.706, 0.741, 0.806, and 0.827, respectively. Serum levels of miR-29a and miR-125b were significantly higher in patients who had only small colorectal neoplasms (?5 mm) than in healthy subjects.Because serum levels of miR-21, miR-29a, and miR-125b discriminated patients with early colorectal neoplasm from healthy controls, our data highlight the potential clinical use of these molecular signatures for noninvasive screening of patients with colorectal neoplasia.
| S-EPMC4573815 | biostudies-literature
Project description:Background: The biological role of microRNAs (miRNAs) in field cancerization is unknown. To investigate the involvement of miRNAs in gastric field cancerization, we evaluated the expression profile of ten miRNAs and their diagnostic value. Methods: We used three groups of FFPE gastric samples: non-cancer (NC), cancer adjacent (ADJ) and gastric cancer (GC). The expression profiles of hsa-miR-10a, -miR-21, -miR-29c, -miR-135b, -miR-148a, -miR-150, -miR-204, -miR-215, -miR-483 and -miR-664a were investigated using qRT-PCR. The results obtained by qRT-PCR were validated in Small RNA-Seq data from the TCGA database. The search for target genes of the studied miRNAs was performed in the miRTarBase public database and miRTargetLink tool, using experimentally validated interactions. In addition, we also performed the functional analysis of these genes using enrichment in KEGG pathways. The potential as biomarker was evaluated using a receiver operating characteristic (ROC) curve and the derived area under the curve (AUC>0.85) analysis. Results: The miRNAs hsa-miR-10a, -miR-21, -miR-135b, hsa-miR-148a, -miR-150, -miR-215, -miR-204, -miR-483 and -miR-664a were up-regulated in ADJ and GC compared to NC (P<0.03); and hsa-miR-21 and -miR-135b were up-regulated in GC compared to ADJ (P<0.01). Hsa-miR-148a, -miR-150, -miR-215, -miR-483 and -miR-664a were not differentially expressed between GC and ADJ, suggesting that both share similar changes (P>0.1). The TS-miR hsa-miR-29c was up-regulated in ADJ compared to NC and GC (P<0.01); we did not observe a significant difference in the expression of this miRNA between NC and GC. This feature may be an antitumor mechanism used by cancer-adjacent tissue because this miRNA regulates the BCL-2, CDC42 and DMNT3A oncogenes. The expression level of hsa-miR-204 was associated with Helicobacter pylori infection status (P<0.05). Functional analysis using the genes regulated by the studied miRNAs showed that they are involved in biological pathways and cellular processes that are critical for the establishment of H. pylori infection and for the onset, development and progression of GC. hsa-miR-10a, -miR-21, -miR-135b, -miR-148a, -miR-150, -miR-215, -miR-483 and -miR-664a were able to discriminate NC from other tissues with great accuracy (AUC>0.85). Conclusion: The studied miRNAs are closely related to field cancerization, regulate genes important for gastric carcinogenesis and can be potentially useful as biomarkers in GC.
| S-EPMC6485221 | biostudies-literature