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Clinical Epigenetics Jul 2022Current noninvasive assays have limitations in the early detection of colorectal cancer. We evaluated the clinical utility of promoter methylation of the long noncoding...
BACKGROUND
Current noninvasive assays have limitations in the early detection of colorectal cancer. We evaluated the clinical utility of promoter methylation of the long noncoding RNA LINC00473 as a noninvasive biomarker to detect colorectal cancer and associated precancerous lesions.
METHODS
We evaluated the epigenetic regulation of LINC00473 through promoter hypermethylation in colorectal cancer cell lines using bisulfite genomic sequencing and expression analyses. DNA methylation of LINC00473 was analyzed in primary colorectal tumors using 450K arrays and RNA-seq from The Cancer Genome Atlas (TCGA). Tissue-based findings were validated in several independent cohorts of colorectal cancer and advanced colorectal polyp patients by pyrosequencing. We explored the clinical utility of LINC00473 methylation for the early detection of colorectal cancer in plasma cell-free DNA by quantitative methylation-specific PCR and droplet digital PCR.
RESULTS
LINC00473 showed transcriptionally silencing due to promoter hypermethylation in colorectal cancer cell lines and primary tumors. Methylation of the LINC00473 promoter accurately detected primary colorectal tumors in two independent clinical cohorts, with areas under the receiver operating characteristic curves (AUCs) of 0.94 and 0.89. This biomarker also identified advanced colorectal polyps from two other tissue-based clinical cohorts with high diagnostic accuracy (AUCs of 0.99 and 0.78). Finally, methylation analysis of the LINC00473 promoter in plasma cell-free DNA accurately identified patients with colorectal cancer and advanced colorectal polyps (AUCs of 0.88 and 0.84, respectively), which was confirmed in an independent cohort of patients.
CONCLUSIONS
Hypermethylation of the LINC00473 promoter is a new promising biomarker for noninvasive early detection of colorectal cancer and related precancerous lesions.
Topics: Biomarkers, Tumor; Cell-Free Nucleic Acids; Colonic Polyps; Colorectal Neoplasms; DNA Methylation; Epigenesis, Genetic; Gene Expression Regulation, Neoplastic; Humans; Precancerous Conditions
PubMed: 35810318
DOI: 10.1186/s13148-022-01302-x -
Therapeutic Advances in... 2021Colonoscopy remains the gold standard exam for colorectal cancer screening due to its ability to detect and resect pre-cancerous lesions in the colon. However, its... (Review)
Review
Colonoscopy remains the gold standard exam for colorectal cancer screening due to its ability to detect and resect pre-cancerous lesions in the colon. However, its performance is greatly operator dependent. Studies have shown that up to one-quarter of colorectal polyps can be missed on a single colonoscopy, leading to high rates of interval colorectal cancer. In addition, the American Society for Gastrointestinal Endoscopy has proposed the "resect-and-discard" and "diagnose-and-leave" strategies for diminutive colorectal polyps to reduce the costs of unnecessary polyp resection and pathology evaluation. However, the performance of optical biopsy has been suboptimal in community practice. With recent improvements in machine-learning techniques, artificial intelligence-assisted computer-aided detection and diagnosis have been increasingly utilized by endoscopists. The application of computer-aided design on real-time colonoscopy has been shown to increase the adenoma detection rate while decreasing the withdrawal time and improve endoscopists' optical biopsy accuracy, while reducing the time to make the diagnosis. These are promising steps toward standardization and improvement of colonoscopy quality, and implementation of "resect-and-discard" and "diagnose-and-leave" strategies. Yet, issues such as real-world applications and regulatory approval need to be addressed before artificial intelligence models can be successfully implemented in clinical practice. In this review, we summarize the recent literature on the application of artificial intelligence for detection and characterization of colorectal polyps and review the limitation of existing artificial intelligence technologies and future directions for this field.
PubMed: 34263163
DOI: 10.1177/26317745211014698 -
British Journal of Cancer Nov 2022Colorectal cancer (CRC) chemoprevention is an area of interest. Non-steroidal anti-inflammatory drugs (NSAIDs) are anti-inflammatory agents which have been identified as... (Review)
Review
Colorectal cancer (CRC) chemoprevention is an area of interest. Non-steroidal anti-inflammatory drugs (NSAIDs) are anti-inflammatory agents which have been identified as cancer chemoprevention agents given that inflammation is thought to contribute to tumorigenesis. Most studies have demonstrated that the NSAID, aspirin, plays a beneficial role in the prevention of CRC and colonic adenomas. Non-aspirin NSAIDs (NA-NSAIDs) have also been studied in CRC chemoprevention. There is increasing literature around their role in pre-cancerous polyp prevention and in decreasing CRC incidence and CRC-related outcomes in certain high-risk subgroups. However, the use of NA-NSAIDs may be accompanied by increased risks of toxicity. Further studies are required to establish the associations between concurrent aspirin and NA-NSAID use, and CRC-related outcomes.
Topics: Humans; Aspirin; Colorectal Neoplasms; Anti-Inflammatory Agents, Non-Steroidal; Adenoma; Anti-Inflammatory Agents
PubMed: 35764787
DOI: 10.1038/s41416-022-01882-8 -
Gastrointestinal Endoscopy Clinics of... Apr 2009Reflectance spectroscopy is an emerging technology which provides rapid and safe evaluation of tissue for dysplasia and ischemia. The probe-based devices can be passed...
Reflectance spectroscopy is an emerging technology which provides rapid and safe evaluation of tissue for dysplasia and ischemia. The probe-based devices can be passed through most endoscopes. Current applications include detection of dysplasia in Barrett's esophagus, colitis, and colon polyps.
Topics: Diagnosis, Differential; Endoscopy, Gastrointestinal; Gastrointestinal Neoplasms; Gastrointestinal Tract; Humans; Ischemia; Light; Precancerous Conditions; Scattering, Radiation; Sensitivity and Specificity; Spectrophotometry
PubMed: 19423021
DOI: 10.1016/j.giec.2009.02.008 -
Biomedical Optics Express Feb 2023Colonoscopy remains the gold standard investigation for colorectal cancer screening as it offers the opportunity to both detect and resect pre-cancerous polyps....
Colonoscopy remains the gold standard investigation for colorectal cancer screening as it offers the opportunity to both detect and resect pre-cancerous polyps. Computer-aided polyp characterisation can determine which polyps need polypectomy and recent deep learning-based approaches have shown promising results as clinical decision support tools. Yet polyp appearance during a procedure can vary, making automatic predictions unstable. In this paper, we investigate the use of spatio-temporal information to improve the performance of lesions classification as adenoma or non-adenoma. Two methods are implemented showing an increase in performance and robustness during extensive experiments both on internal and openly available benchmark datasets.
PubMed: 36874484
DOI: 10.1364/BOE.473446 -
PeerJ 2023Colorectal cancer (CRC), which develops from the gradual evolution of tubular adenomas and serrated polyps in the colon and rectum, has a poor prognosis and a high... (Review)
Review
Colorectal cancer (CRC), which develops from the gradual evolution of tubular adenomas and serrated polyps in the colon and rectum, has a poor prognosis and a high mortality rate. In addition to genetics, lifestyle, and chronic diseases, intestinal integrity and microbiota (which facilitate digestion, metabolism, and immune regulation) could promote CRC development. For example, enterotoxigenic , genotoxic , and , members of the intestinal microbiota, are highly correlated in CRC. This review describes the roles and mechanisms of these three bacteria in CRC development. Their interaction during CRC initiation and progression has also been proposed. Our view is that in the precancerous stage of colorectal cancer, ETBF causes inflammation, leading to potential changes in intestinal ecology that may provide the basic conditions for pks+ colonization and induction of oncogenic mutations, when cancerous intestinal epithelial cells can further recruit to colonise the lesion site and may contribute to CRC advancement by primarily the development of cancer cells, stemization, and proliferation, which could create new and tailored preventive, screening and therapeutic interventions. However, there is the most dominant microbiota in each stage of CRC development, not neglecting the possibility that two or even all three bacteria could be engaged at any stage of the disease. The relationship between the associated gut microbiota and CRC development may provide important information for therapeutic strategies to assess the potential use of the associated gut microbiota in CRC studies, antibiotic therapy, and prevention strategies.
Topics: Humans; Colorectal Neoplasms; Escherichia coli; Bacteria; Rectum
PubMed: 37554340
DOI: 10.7717/peerj.15777 -
Cancers Jun 2021Gut microbiota plays an important role in human health. It may promote carcinogenesis and is related to several diseases of the gastrointestinal tract. This study of... (Review)
Review
Gut microbiota plays an important role in human health. It may promote carcinogenesis and is related to several diseases of the gastrointestinal tract. This study of microbial dysbiosis in the etiology of colorectal adenoma aimed to investigate the possible causative role of microbiota in the adenoma-carcinoma sequence and its possible preventive role. A systematic, PRISMA-guided review was performed. The PubMed database was searched using "adenoma microbiota" and selecting original articles between January 2010 and May 2020 independently screened. A higher prevalence of Proteobacteria, Fusobacteria, and Bacteroidetes phyla was observed in the fecal luminal and mucosa-associated microbiota of patients with adenoma. However, other studies provided evidence of depletion of , , and . Results on the relationship between adenoma endoscopic resection and microbiota were inconsistent. In conclusion, none of the analyzed studies developed a predictive model that could differentiate adenoma from non-adenoma patients, and therefore, to prevent cancer progression. The impact of adenoma's endoscopic resection on microbiota was investigated, but the results were inconclusive. Further research in the field is required.
PubMed: 34205378
DOI: 10.3390/cancers13123061 -
World Journal of Gastroenterology Feb 2019During the past decades, endoscopic resection techniques have gradually improved and gained more importance for the management of premalignant lesions and early cancers.... (Review)
Review
During the past decades, endoscopic resection techniques have gradually improved and gained more importance for the management of premalignant lesions and early cancers. These endoscopic resection techniques can be divided in 3 major groups: snare polipectomy, endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). The use of submucosal injection is essential for the majority of EMR techniques and is an integral part of ESD, whereas during polipectomy it is not crucial in most cases except to prevent bleeding in large polyps and/or those with large stalks as an alternative to mechanical methods. Injection provides a lifting up effect of the lesion separating it from the muscular layer, thereby reducing thermal injury and the risk of perforation and bleeding while also facilitating resection by improving technical feasibility. With this work, we aim to review the most common endoscopic resection techniques and the importance of submucosal injection in each one of them. For that, we present some of the most commonly used submucosal injection solutions, taking into account their advantages and disadvantages. We also discuss, based on current recommendations and our own experience, how and when to preform submucosal injection, depending on lesions features and endoscopic resection technique that´s being used, to assure complete resection and to prevent associated adverse events. Finally, we also present and discuss some new proposed submucosal injection solutions, endoscopic resection techniques and devices that may have a major impact on the future of therapeutic endoscopy.
Topics: Endoscopic Mucosal Resection; Gastric Mucosa; Gastrointestinal Diseases; Humans; Injections; Intestinal Mucosa; Neoplasms; Precancerous Conditions
PubMed: 30809079
DOI: 10.3748/wjg.v25.i7.777 -
Journal of Clinical Pathology Apr 2001Advances in molecular biology have increased our knowledge of the biology of preneoplastic lesions in the human lung. The recently published WHO lung tumour... (Review)
Review
Advances in molecular biology have increased our knowledge of the biology of preneoplastic lesions in the human lung. The recently published WHO lung tumour classification defines three separate lesions that are regarded as preinvasive neoplasia. These are (1) squamous dysplasia and carcinoma in situ (SD/CIS), (2) atypical adenomatous hyperplasia (AAH), and (3) diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIP-NECH). SD/CIS is graded in four stages (mild, moderate, severe, and CIS), based upon the distribution of atypical cells and mitotic figures. Most airways showing SD/CIS demonstrate a range of grades; many epithelia are hard to assess and the reproducibility of this complex system remains to be established. Detailed criteria are, however, welcome and provide an objective framework on which to compare various molecular changes. Alterations in gene expression and chromosome structure known to be associated with malignant transformation can be demonstrated in CIS, less so in dysplasias, but also in morphologically normal epithelium. The changes might be sequential, and their frequency and number increase with atypia. Less is known of the "risk of progression" of SD/CIS to invasive "central" bronchial carcinoma. It may take between one and 10 years for invasion to occur, yet the lesion(s) may be reversible if carcinogen exposure ceases. AAH may be an important precursor lesion for peripheral "parenchymal" adenocarcinoma of the lung: the "adenoma" in an adenoma-carcinoma sequence. There is good morphological evidence that AAH may progress from low to high grade to bronchioloalveolar carcinoma (BAC; a non-invasive lesion by definition). Invasion then develops within BAC and peripheral lung adenocarcinoma evolves. The molecular events associated with this progression are not well understood and studies are hampered by a lack of clear criteria to distinguish high grade AAH from BAC. Nonetheless, as with SD/CIS, the patterns of expression of tumour associated genes are consistent with neoplastic progression. We have little idea of the incidence of AAH in the normal or "smoking" populations. It is found more frequently in cancer bearing lungs, especially in those with adenocarcinoma, and is more common in women. No data are available on the risk of progression of AAH. DIPNECH is an exceptionally rare lesion associated with the development of multiple carcinoid tumours. Almost nothing is known of its biology. Knowledge of these lesions will be crucial in the design and understanding of lung cancer screening programmes, where it is likely that the morphological and, more importantly perhaps, the molecular characteristics of these lesions will provide useful targets for detection and possibly even treatment.
Topics: Adenocarcinoma; Adenomatous Polyps; Carcinoma in Situ; Carcinoma, Bronchogenic; Carcinoma, Neuroendocrine; Disease Progression; Epithelium; Female; Humans; Hyperplasia; Lung Neoplasms; Male; Precancerous Conditions
PubMed: 11304841
DOI: 10.1136/jcp.54.4.257 -
Frontiers in Artificial Intelligence 2022Colorectal Cancer (CRC) has seen a dramatic increase in incidence globally. In 2019, colorectal cancer accounted for 1.15 million deaths and 24.28 million... (Review)
Review
Colorectal Cancer (CRC) has seen a dramatic increase in incidence globally. In 2019, colorectal cancer accounted for 1.15 million deaths and 24.28 million disability-adjusted life-years (DALYs) worldwide. In India, the annual incidence rates (AARs) for colon cancer was 4.4 per 100,000. There has been a steady rise in the prevalence of CRC in India which may be attributed to urbanization, mass migration of population, westernization of diet and lifestyle practices and a rise of obesity and metabolic risk factors that place the population at a higher risk of CRC. Moreoever, CRC in India differs from that described in the Western countries, with a higher proportion of young patients and more patients presenting with an advanced stage. This may be due to poor access to specialized healthcare and socio-economic factors. Early identification of adenomatous colonic polyps, which are well-recognized pre-cancerous lesions, at the time of screening colonoscopy has been shown to be the most effective measure used for CRC prevention. However, colonic polyps are frequently missed during colonoscopy and moreover, these screening programs necessitate man-power, time and resources for processing resected polyps, that may hamper penetration and efficacy in mid- to low-income countries. In the last decade, there has been significant progress made in the automatic detection of colonic polyps by multiple AI-based systems. With the advent of better AI methodology, the focus has shifted from mere detection to accurate discrimination and diagnosis of colonic polyps. These systems, once validated, could usher in a new era in Colorectal Cancer (CRC) prevention programs which would center around "Leave " and "Resect and discard" strategies. These new strategies hinge around the specificity and accuracy of AI based systems in correctly identifying the pathological diagnosis of the polyps, thereby providing the endoscopist with real-time information in order to make a clinical decision of either leaving the lesion (mucosal polyps) or resecting and discarding the polyp (hyperplastic polyps). The major advantage of employing these strategies would be in cost optimization of CRC prevention programs while ensuring good clinical outcomes. The adoption of these AI-based systems in the national cancer prevention program of India in accordance with the mandate to increase technology integration could prove to be cost-effective and enable implementation of CRC prevention programs at the population level. This level of penetration could potentially reduce the incidence of CRC and improve patient survival by enabling early diagnosis and treatment. In this review, we will highlight key advancements made in the field of AI in the identification of polyps during colonoscopy and explore the role of AI based systems in cost optimization during the universal implementation of CRC prevention programs in the context of mid-income countries like India.
PubMed: 36248620
DOI: 10.3389/frai.2022.955399