Identification of microRNAs as blood-based markers for colorectal cancer

鉴定 microRNA 作为结直肠癌的血液标记物

• 批准号: 8122674
• 负责人: STANLEY R. HAMILTON
• 金额: $ 20.62万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8122674
• 关键词: Address; Adjuvant Chemotherapy; Area; Base Pairing; Biological Assay; Biological Markers; Blood; Blood Tests; Cancer Detection; Cancer Etiology; Cancer Patient; Carcinoembryonic Antigen; Cessation of life; Characteristics; Clinical; Colon Carcinoma; Colorectal Cancer; Complement; Coupled; Data; Data Analyses; Death Rate; Detection; Development; Disease; Disease Progression; Distant; Distant Metastasis; Early Diagnosis; Epithelial; Excision; Family; Functional RNA; Future; Gene Expression; Gene Targeting; Individual; Investigation; Localized Disease; Malignant Neoplasms; Mesenchymal; MicroRNAs; Monitor; Neoadjuvant Therapy; Neoplasm Metastasis; Patients; Performance; Pilot Projects; Plasma; Publishing; RNA; Recurrence; Reverse Transcriptase Polymerase Chain Reaction; Sampling; Screening for cancer; Staging; Stratification; Technology; Testing; Translational Repression; United States; Validation; base; chemotherapy; clinically relevant; cohort; colorectal cancer screening; density; improved; lymph nodes; member; metastatic colorectal; next generation; novel; outcome forecast; prevent; prognostic; response; therapy outcome

DESCRIPTION (provided by applicant): Colorectal cancer (CRC) is the second most common cause of cancer-related death in the United States, with estimated 51,370 deaths in 2010 according to NCI. Even though the 5-year death rate of CRC has declined over the past three decades, further progress has been hindered by suboptimal compliance with strategies that can prevent and detect CRC in its early stages, monitor disease progression and predict therapy outcome. Thus, development of non- invasive, simple but accurate tests is needed. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression through non-perfect base-pairing. Recently, accumulating evidence has indicated that aberrant expression of miRNAs is associated with cancer development and progression. The use of circulating miRNAs as biomarkers has begun to be investigated and published in a few studies. A successful blood test would be a major help in deciding on neoadjuvant or adjuvant chemotherapy, and would also be used to follow patients for recurrence after curative resection and after chemotherapy for response. In a pilot study, using TaqMan qRT-PCR based miRNA assays we compared expression of 5 selected miRNAs in a cohort of 85 plasma samples from healthy donors, CRC patients with localized disease, and CRC patients with distant metastatic disease. Our preliminary data showed that all of these miRNAs can be detected in the plasma. Further, the levels of miR-141, a member of the miR-200 family, were significantly elevated in plasma samples from patients with distant metastatic colorectal cancer. Our preliminary data support our hypothesis that specific miRNAs can be used as non-invasive, blood-based markers for early detection, stage stratification and prediction of prognosis in CRC. Our overall objective is to identify and put into routine usage a set of robust plasma miRNA markers for CRC early detection, monitoring early metastasis and evaluating prognosis. PUBLIC HEALTH RELEVANCE: Although the search for plasma markers for cancer is a well-established concept, the finding of markers that are clinically useful is very infrequent. Any marker with favorable performance characteristics would favorably impact cancer screening and monitoring and contribute to improved survival of patients. Therefore, the search for plasma markers for colon cancer in this proposal is critically important.

描述（由申请人提供）：结直肠癌（CRC）是美国与癌症相关死亡的第二大原因，根据NCI的数据，2010年估计有51,370例死亡。尽管在过去的三十年中，CRC的5年死亡率下降了，但由于对可以在早期阶段预防和检测CRC的策略的依从性而阻碍了进一步的进展，监测疾病进展并预测治疗结果。因此，需要开发非侵入性，简单但准确的测试。 microRNA（miRNA）是小的非编码RNA，可通过不完美的碱基对调节基因表达。最近，积累的证据表明，miRNA的异常表达与癌症的发展和进展有关。将循环miRNA用作生物标志物的使用已开始在一些研究中进行研究和发表。成功的血液检查将是决定新辅助或辅助化疗的主要帮助，并且还将用于跟随患者在治愈后切除和化学疗法后复发。在一项试点研究中，使用基于TAQMAN QRT-PCR的miRNA分析，我们比较了来自健康供体的85个血浆样品，患有局部疾病的CRC患者和CRC远处转移性疾病的55个血浆样本中的5个选定miRNA的表达。我们的初步数据表明，可以在血浆中检测到所有这些miRNA。此外，MiR-141的水平是miR-200家族的成员，在远处转移性结直肠癌患者的血浆样品中显着升高。我们的初步数据支持我们的假设，即特定的miRNA可以用作非侵入性的，基于血液的标记，用于早期检测，阶段分层和预测CRC中的预测。我们的总体目标是识别并将常规用法用于CRC早期检测，监测早期转移并评估预后的一组健壮的等离子体miRNA标记。 公共卫生相关性：尽管寻找癌症的等离子体标记是一个公认的概念，但在临床上有用的标记发现很少见。任何具有良好表现特征的标记物都会有利地影响癌症筛查和监测，并有助于改善患者的生存率。因此，在该提案中寻找针对结肠癌的血浆标志物至关重要。