Biomarkers for Early Detection of Colorectal Cancer in Ulcerative Colitis

溃疡性结肠炎(UC)是一种慢性炎症性结肠疾病。广泛性UC超过 病程8年的人患结直肠癌(CRC)的风险增加，每年约为0.5%-1% 结肠炎；这导致建议终身监测结肠镜检查。然而，对癌症的监测 这些患者昂贵、耗时且具有侵入性。此外，检出异型增生的敏感度 结肠镜检查只是中等程度的，主要是因为在结肠镜检查的背景下很难发现扁平的不典型增生病变 加州大学。异型增生的客观分子生物学标记物在临床治疗中具有重要的价值。 UC患者的癌症风险。在我们为UC异型增生开发生物标记物的努力中，我们先前发现 在UC患者的其他部位有肿瘤的UC患者的非发育不良粘膜是遗传异常的 冒号(进行词)，即UC进行词中存在非UC中不存在的场缺陷现象 进展者(无异型增生的患者)。最近，我们进一步发现，相同的场缺陷扩展到 溃疡性结肠炎患者直肠非发育不良黏膜中蛋白质的异常表达这些 这些发现是令人兴奋的，因为这些蛋白质变化发生在随机抽样的结肠和/或直肠粘膜中 无论是否存在不典型增生。这些异常表达的蛋白质可能对 开发有效且相对非侵入性的生物标记物来检测UC异型增生。一个人可以 想象一下，从未准备好的直肠进行随机活检将足以提供所需的样本 生物标记物检测。这项提议寻求开发分子生物标记物用于两个目的：1)检测电流 异型增生/癌症；2)预测(跟踪)未来的异型增生/癌症进展。分子生物标记物将是 通过使用尖端定量技术开发，然后使用免疫组织化学进行评估和验证 (IHC)和靶向蛋白质组学方法。最后，对分子生物标记物的临床应用进行评估。 在不同队列中检测和预测UC肿瘤进展的价值。我们相信，这个项目将 大大改进目前早期发现UC相关结直肠癌的监测策略。

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.