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患者 8年的持续时间会增加结直肠癌（CRC）的风险，每年约为0.5-1%。 结肠炎;这导致终身监测结肠镜检查的建议。然而，癌症监测 这些患者是昂贵的、耗时的和侵入性的。此外，检测发育异常的敏感性， 结肠镜检查只是中度的，主要是由于在结肠镜检查的背景下难以检测扁平的发育不良病变。 加州大学一种客观的异型增生分子生物学标记物将在管理异型增生中具有重要的临床价值。 UC患者的癌症风险。在我们为UC异型增生的生物标志物开发的努力中，我们以前发现， 在UC患者中，非异型增生粘膜在遗传上是异常的， 结肠（进展者），即在UC进展者中存在场缺陷现象，这在UC非进展者中不存在。 进展者（无发育不良的患者）。最近，我们进一步发现，同样的场缺陷延伸到 UC进展者直肠的非异型增生粘膜中蛋白质的异常表达。这些 这些发现令人兴奋，因为这些蛋白质变化发生在随机取样的结肠和/或直肠粘膜中 无论是否存在发育异常。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用于检测UC异型增生的生物标志物。人能 设想从未经准备的直肠随机活检足以提供所需的样本， 生物标志物检测该提议寻求开发用于两个目的的分子生物标志物：1）检测电流 2）预测（跟踪）未来的发育异常/癌症进展。分子生物标志物将是 通过使用尖端定量开发，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，将评价分子生物标志物的临床应用。 在不同队列中检测和预测UC肿瘤进展的价值。我们相信，该项目将 大大改善了目前早期发现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.