Diagnostic Potential of Hypermethylated DNA in Colorectal Cancer
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 658
- 试验地点
- 1
- 主要终点
- Diagnostic potential of hypermethylated DNA as a biomarker for colorectal cancer
研究概览
简要总结
Colorectal cancer (CRC) is one of the most common forms of cancer and the second leading cause of cancer-related deaths in the western world.
CRC mortality is related to stage of disease with a five year survival for early-stage disease of 77.0% and 50.8% for late stage disease. Methods for early detection of primary as well as recurrent CRC are therefore important to increase patient survival. Tumour biomarkers from blood, stool, or urine could aid the early diagnostics of CRC, but despite extensive research such markers have only provided limited clinical value.
Sporadic CRC develops as a result of the accumulation of genetic and epigenetic alterations. Epigenetic alterations include DNA hypermethylation, which through transcriptional silencing of tumour suppressor genes is associated with cancer development and cancer progression. The search for gene promoter regions hypermethylated in cancer has been ongoing for nearly two decades, and a number of genes have been shown to be preferentially hypermethylated in CRC. Therefore, hypermethylated DNA in plasma has been suggested as a marker for tumour-stage and survival in CRC patients. The only approved biomarker for the detection of CRC recurrence is the protein carcinoembryonic antigen (CEA). CEA is limited by its low sensitivity and therefore not recommended as a diagnostic biomarker. Hypermethylation of CRC specific genes as part of a molecular biomarker panel measured in blood could prove to be a recurrence marker in CRC patients, with elevated sensitivity and specificity.
The aims of this project are to examine if hypermethylation of specific genes measured from cell-free DNA in plasma of CRC patients can be used to detect primary CRC, to detect CRC recurrence and to be a biomarker for CRC prognosis.
Development of a reliable sensitive and specific biomarker for CRC will immensely improve the diagnostics and handling of CRC patients.
详细描述
Colorectal cancer (CRC) is one of the most common forms of cancer and the second leading cause of cancer-related deaths in the western world, accounting for the annual death of 215.000 europeans in 2012 and an estimated 50.310 Americans in 2014.
Sporadic CRC develops through the accumulation of genetic and epigenetic alterations in the epithelial cell-lining. These alterations are thought to push the normal epithelial cells into the adenoma-carcinoma sequence. Detection of hypermethylated DNA can be made in blood or stool of cancer patients and it is believed, that hypermethylated cell-free DNA in blood and stool can be used as a cancer biomarker, exhibiting high sensitivity and specificity in CRC and other major cancer-types (e.g. lung, prostate, and breast cancer).
Hypermethylated cell-free DNA - measured in plasma - could prove to be a more specific and sensitive biomarker for CRC than both the detection of blood in stool and CEA in blood of CRC patients.
The aims of this project are to examine if hypermethylation of specific genes measured from cell-free DNA in plasma of CRC patients is a diagnostic biomarker for CRC. The results of this study will show, if a single blood sample can differentiate patients with CRC from patients without cancer.
Development of a reliable sensitive and specific biomarker for CRC will immensely improve the diagnostics and handling of CRC patients.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patients followed in the outpatient clinic with ulcerative colitis at Aalborg University Hospital.
- •Patients with a positive fecal occult blood test, referred for colonoscopy
排除标准
- •Prior cancer history
- •Previous total colectomy
结局指标
主要结局
Diagnostic potential of hypermethylated DNA as a biomarker for colorectal cancer
时间窗: At the time of inclusion
Through the analysis of cell-free DNA, we will develop a diagnostic prediction model for colorectal cancer using hypermethylated DNA as a biomarker. Hypermethylation status will be analysed using real time PCR. The model will be developed using plasma samples from 193 colorectal cancer patients and 102 healthy controls. The subsequent validation of the model, will be conducted, using plasma samples from 143 colorectal cancer patients, and roughly 100 colonoscopy verified healthy controls. In the validation study, we will also analyse plasma samples from roughly 100 patients with ulcerative colitis, in order to make sure, that the model can distinguish these patients from the other groups.
次要结局
- Prognostic potential of hypermethylated DNA for colorectal cancer stage(From the time of inclusion up to five years)
- Hypermethylated DNA as a follow-up biomarker for disease recurrence(From the time of inclusion and to the time of recurrence, or five years)
研究者
Ole Thorlacius-Ussing, MD, DMSc, Professor of Surgery
MD, DMSc
Aalborg University Hospital