Biomarkers for Early Detection of Colorectal Cancer in Ulcerative Colitis

溃疡性结肠炎中结直肠癌早期检测的生物标志物

• 批准号: 9700068
• 负责人: Ru Chen
• 金额: $ 44.78万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-19 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9700068
• 关键词: Bioinformatics; Biological Markers; Biopsy; CYP21A2 gene; Cancer Detection; Case-Control Studies; Clinical; Colectomy; Colitis; Colitis associated colorectal cancer; Colon; Colonoscopy; Communities; Consumption; Cost Savings; DNA; Defect; Detection; Diagnosis; Dysplasia; Early Diagnosis; Ensure; Future; Genomics; High grade dysplasia; Immunohistochemistry; Intervention; Knowledge; Lesion; Life; Malignant Neoplasms; Methods; Mucous Membrane; Neoplasms; Patient risk; Patients; Physicians; Prospective Studies; Prospective cohort; Proteins; Proteomics; Protocols documentation; Recommendation; Rectum; Sampling; Savings; Severities; Societies; Specificity; Testing; Time; Ulcerative Colitis; base; biomarker development; biomarker evaluation; biomarker panel; biomarker validation; cancer risk; cancer therapy; candidate marker; case control; chromoscopy; chronic inflammatory disease; clinically relevant; cohort; colon cancer risk; colorectal cancer risk; colorectal cancer screening; cost; cost effective; early detection biomarkers; follow-up; high risk; improved; molecular marker; neoplastic; predictive panel; preference; protein expression; proteomic signature; rectal; surveillance strategy; tissue biomarkers; tumor progression

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon. Patients with extensive UC of more than 8 years duration have an increased risk of colorectal cancer (CRC) which approximates 0.5-1% per year of colitis; this leads to a recommendation for life-long surveillance colonoscopy. However, cancer surveillance for these patients is expensive, time-consuming and invasive. Moreover, the sensitivity of detecting dysplasia in colonoscopy is only moderate, largely due to the difficulty in detecting flat dysplastic lesions in the setting of UC. An objective molecular biomarker for dysplasia would have great clinical value in the management of cancer risk in UC patients. In our efforts for biomarker development for UC dysplasia, we previously discovered that the non-dysplastic mucosa is genetically abnormal in UC patients who have neoplasia elsewhere in their colon (progressors), i.e. there is a field defect phenomenon in UC progressors which is not present in UC non- progressors (patients without dysplasia). Recently, we further discovered that the same field defect extends to abnormal expression of proteins in the non-dysplastic mucosa from the rectum of UC progressors. These findings are exciting because these protein changes occur in randomly sampled colon and/or rectal mucosa regardless of whether dysplasia is present or not. These abnormally expressed proteins could be valuable for developing biomarkers that are effective and relatively non-invasive for detecting UC dysplasia. One can envision that a random biopsy from an unprepped rectum would suffice to provide the sample needed for biomarker testing. This proposal seeks to develop molecular biomarkers for two purposes: 1) to detect current dysplasia/cancer; 2) to predict (track) future dysplasia/cancer progression. Molecular biomarkers will be developed by using cutting edge quantitative and then evaluated and validated using immunohistochemistry (IHC) and targeted proteomics methods. Finally, the molecular biomarkers will be evaluated for their clinical value in detecting and predicting UC neoplasia progression in different cohorts. We believe that this project will greatly improve the current surveillance strategy for early detection of UC-associated colorectal cancer.

溃疡性结肠炎（UC）是结肠的慢性炎症性疾病。大量UC的患者超过 8年的持续时间增加了结直肠癌（CRC）的风险，每年约0.5-1％ 结肠炎;这导致了对终身监测结肠镜检查的建议。但是，癌症监测 这些患者昂贵，耗时且侵入性。此外，检测发育不良的敏感性 结肠镜检查仅是中等的，这主要是由于难以检测平坦的发育不良病变。 UC。异常发育不良的客观分子生物标志物在管理方面具有巨大的临床价值 UC患者的癌症风险。在我们为UC发育不良开发生物标志物开发的努力中，我们以前发现了 在其其他地方有肿瘤的UC患者中，非塑性粘膜在遗传上是异常的 结肠（进度者），即加州大学进步者中存在一种现场缺陷现象 进度者（没有发育不良的患者）。最近，我们进一步发现相同的场缺陷延伸到 从UC进展者直肠直肠粘膜中蛋白质异常表达。这些 发现令人兴奋，因为这些蛋白质变化发生在随机采样的结肠和/或直肠粘膜中 无论发育不良是否存在。这些异常表达的蛋白质可能对 开发有效且相对无创的生物标志物检测UC发育不良。一个人可以 设想从未经修复直肠进行的随机活检就足以提供所需的样本 生物标志物测试。该建议旨在开发两个目的的分子生物标志物：1）检测电流 发育不良/癌症； 2）预测（轨道）未来的发育不良/癌症进展。分子生物标志物将是 通过使用尖端定量进行开发，然后使用免疫组织化进行评估和验证 （IHC）和靶向蛋白质组学方法。最后，将评估分子生物标志物的临床 检测和预测不同队列中UC肿瘤进展的价值。我们相信这个项目将 大大改善了当前的监视策略，用于早期检测到与UC相关的结直肠癌。