免费获得国外相关药品，最快 1 个工作日回馈药物信息
The Predictive Value of Guangzhou Panel for Recurrence in Early-stage Colorectal Cancer
| Condition or disease | Intervention/treatment |
|---|---|
| Colorectal Neoplasms | Other: DNA methylation detection |
The current risk stratification system defined by clinicopathological features does not identify the risk of disease recurrence in patients with early-stage colorectal cancer (CRC) with optimal accuracy. The investigators aimed to investigate whether the epigenetic alterations could serve as novel prognostic biomarkers that would improve the accuracy of the current primary tumor, regional nodes, metastasis (TNM) staging system.
In the current study, the Investigators have analyzed the genome-wide methylation status of cytosine-phosphate-guanosine (CpG) sites using Infinium MethylationEPIC array in primary tumor and adjacent normal samples from 23 recurrent and 22 recurrence-free stage I and II CRC patients to identify potential methylation markers for disease-free survival (DFS). The prognostic value of the candidate biomarkers has been evaluated in a training cohort (n=174) and an independent validation cohort (n=267), and is to be validated in a prospective cohort (estimated n=287).
Comprehensive data analysis identified a subset of methylated CpG loci that associated with a high risk of recurrence. Methylated CpGs in four genes were significantly associated with DFS in multivariate analysis in both training and validation cohort. Moreover, Hypermethylated Genes Counts panel using these four markers showed a higher prognostic value than any clinicopathological factor, current molecular biomarkers or single methylated CpG marker alone in the training and validation cohorts. This four-gene methylation assay is defined as Guangzhou Panel.
The investigators aim to conduct a prospective observational study to evaluate the predictive value of Guangzhou Panel in early-stage colorectal cancer. A total of 287 patients with pathologically verified stage I-II CRC and underwent surgical resection are expected to be recruited in our study. These patients will be divided into high-risk group and low-risk group and will be followed up at least 5 years. The primary endpoint is 5-year disease free survival (DFS). The prognostic strength of candidate biomarkers was adjusted in multivariate Cox regression models including multiple biomarkers and clinicopathologic variables.
| Study Type : | Observational |
| Estimated Enrollment : | 287 participants |
| Observational Model: | Cohort |
| Time Perspective: | Prospective |
| Official Title: | The Predictive Value of Guangzhou Panel for Recurrence in Early-stage Colorectal Cancer |
| Estimated Study Start Date : | April 30, 2019 |
| Estimated Primary Completion Date : | April 30, 2021 |
| Estimated Study Completion Date : | December 31, 2026 |
| Group/Cohort | Intervention/treatment |
|---|---|
|
high-risk group
patients with any of the four genes hypermethylated
|
Other: DNA methylation detection
detecting the methylation status of colorectal cancer specimen
|
|
low-risk group
patients with none of the four genes hypermethylated
|
Other: DNA methylation detection
detecting the methylation status of colorectal cancer specimen
|
- disease free survival [ Time Frame: From date of operation until the date of first recurrence or date of death from any cause, whichever came first, assessed up to 5 years ]the length of time after primary treatment for a cancer ends that the patient survives without any signs or symptoms of that cancer
Biospecimen Retention: Samples With DNA
| Ages Eligible for Study: | 40 Years to 70 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
| Sampling Method: | Non-Probability Sample |
Inclusion Criteria:
- TNM stage I-II (T1-4N0M0) colorectal cancer cases
- receive radical surgical resection
- have completed data of tumor location, histological type, behavioral characteristics or TNM staging
- have tumor specimens and either a valid microsatellite instability (MSI) or immuno-histochemistry (IHC) data
- have valid V-raf murine sarcoma viral oncogene homolog B1 (BRAF), kirsten rat sarcoma viral oncogene (KRAS), CpG island methylator phenotype (CIMP) results
- have at least 4 years of follow-up
- have valid time to local recurrence/metastasis in follow-up
- have clinical/treatment record data and valid preoperative status of intestinal obstruction or perforation (IOP), counts of lymph node removed in surgical resection.
Exclusion Criteria:
- have had a previous diagnosis of any cancer or presence of any tumor other than the CRC
- have had inflammatory bowel disease
- have had hereditary colorectal cancer syndromes, including Familial adenomatous polyposis, mutyh (MYH)-associated polyposis, Peutz-Jeghers syndrome, Juvenile polyposis coli, phosphate and tension homology deleted on chromosome ten (PTEN) tumor-hamartoma syndromes, Lynch Syndrome, and Familial Colorectal Cancer Type X.
| Contact: Yanxin Luo, MD,PhD | +86-13826190263 | luoyx25@mail.sysu.edu.cn | |
| Contact: Du Cai, MD | +86-18819481550 | caid6@mail2.sysu.edu.cn |
| China, Guangdong | |
| The Sixth Affiliate Hospital of Sun Yat-Sen University | |
| Guangzhou, Guangdong, China, 510655 | |
| Contact: Yanxin Luo, PhD,MD +86-13826190263 luoyx25@mail.sysu.edu.cn | |
| Contact: Du Cai, MD +86-18819481550 caid6@mail2.sysu.edu.cn | |
| Principal Investigator: | Yanxin Luo, MD,PhD | The Sixth Affiliated Hospital, Sun Yat-sen University |
| Tracking Information | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| First Submitted Date | April 14, 2019 | ||||||||
| First Posted Date | April 22, 2019 | ||||||||
| Last Update Posted Date | April 22, 2019 | ||||||||
| Estimated Study Start Date | April 30, 2019 | ||||||||
| Estimated Primary Completion Date | April 30, 2021 (Final data collection date for primary outcome measure) | ||||||||
| Current Primary Outcome Measures |
disease free survival [ Time Frame: From date of operation until the date of first recurrence or date of death from any cause, whichever came first, assessed up to 5 years ] the length of time after primary treatment for a cancer ends that the patient survives without any signs or symptoms of that cancer
|
||||||||
| Original Primary Outcome Measures | Same as current | ||||||||
| Change History | No Changes Posted | ||||||||
| Current Secondary Outcome Measures | Not Provided | ||||||||
| Original Secondary Outcome Measures | Not Provided | ||||||||
| Current Other Pre-specified Outcome Measures | Not Provided | ||||||||
| Original Other Pre-specified Outcome Measures | Not Provided | ||||||||
| Descriptive Information | |||||||||
| Brief Title | The Predictive Value of Guangzhou Panel for Recurrence in Early-stage Colorectal Cancer | ||||||||
| Official Title | The Predictive Value of Guangzhou Panel for Recurrence in Early-stage Colorectal Cancer | ||||||||
| Brief Summary | This study aims to evaluate the predictive value of a four-gene methylation assay called Guangzhou Panel in early-stage colorectal cancer. Patients will be divided into two groups: high risk group and low risk group. The primary endpoint is 5 year disease free survival (DFS). | ||||||||
| Detailed Description |
The current risk stratification system defined by clinicopathological features does not identify the risk of disease recurrence in patients with early-stage colorectal cancer (CRC) with optimal accuracy. The investigators aimed to investigate whether the epigenetic alterations could serve as novel prognostic biomarkers that would improve the accuracy of the current primary tumor, regional nodes, metastasis (TNM) staging system. In the current study, the Investigators have analyzed the genome-wide methylation status of cytosine-phosphate-guanosine (CpG) sites using Infinium MethylationEPIC array in primary tumor and adjacent normal samples from 23 recurrent and 22 recurrence-free stage I and II CRC patients to identify potential methylation markers for disease-free survival (DFS). The prognostic value of the candidate biomarkers has been evaluated in a training cohort (n=174) and an independent validation cohort (n=267), and is to be validated in a prospective cohort (estimated n=287). Comprehensive data analysis identified a subset of methylated CpG loci that associated with a high risk of recurrence. Methylated CpGs in four genes were significantly associated with DFS in multivariate analysis in both training and validation cohort. Moreover, Hypermethylated Genes Counts panel using these four markers showed a higher prognostic value than any clinicopathological factor, current molecular biomarkers or single methylated CpG marker alone in the training and validation cohorts. This four-gene methylation assay is defined as Guangzhou Panel. The investigators aim to conduct a prospective observational study to evaluate the predictive value of Guangzhou Panel in early-stage colorectal cancer. A total of 287 patients with pathologically verified stage I-II CRC and underwent surgical resection are expected to be recruited in our study. These patients will be divided into high-risk group and low-risk group and will be followed up at least 5 years. The primary endpoint is 5-year disease free survival (DFS). The prognostic strength of candidate biomarkers was adjusted in multivariate Cox regression models including multiple biomarkers and clinicopathologic variables. |
||||||||
| Study Type | Observational | ||||||||
| Study Design | Observational Model: Cohort Time Perspective: Prospective |
||||||||
| Target Follow-Up Duration | Not Provided | ||||||||
| Biospecimen | Retention: Samples With DNA Description:
tissue specimen from colorectal cancer patients who underwent radical resection
|
||||||||
| Sampling Method | Non-Probability Sample | ||||||||
| Study Population | patients that had pathologically verified stage I-II CRC and underwent surgical resection in Sixth Affiliate Hospital of Sun Yat-sen University | ||||||||
| Condition | Colorectal Neoplasms | ||||||||
| Intervention | Other: DNA methylation detection
detecting the methylation status of colorectal cancer specimen
|
||||||||
| Study Groups/Cohorts |
|
||||||||
| Publications * |
|
||||||||
|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
|||||||||
| Recruitment Information | |||||||||
| Recruitment Status | Not yet recruiting | ||||||||
| Estimated Enrollment |
287 | ||||||||
| Original Estimated Enrollment | Same as current | ||||||||
| Estimated Study Completion Date | December 31, 2026 | ||||||||
| Estimated Primary Completion Date | April 30, 2021 (Final data collection date for primary outcome measure) | ||||||||
| Eligibility Criteria |
Inclusion Criteria:
Exclusion Criteria:
|
||||||||
| Sex/Gender |
|
||||||||
| Ages | 40 Years to 70 Years (Adult, Older Adult) | ||||||||
| Accepts Healthy Volunteers | No | ||||||||
| Contacts |
|
||||||||
| Listed Location Countries | China | ||||||||
| Removed Location Countries | |||||||||
| Administrative Information | |||||||||
| NCT Number | NCT03923335 | ||||||||
| Other Study ID Numbers | Luo-20190326 | ||||||||
| Has Data Monitoring Committee | No | ||||||||
| U.S. FDA-regulated Product |
|
||||||||
| IPD Sharing Statement |
|
||||||||
| Responsible Party | Sixth Affiliated Hospital, Sun Yat-sen University | ||||||||
| Study Sponsor | Sixth Affiliated Hospital, Sun Yat-sen University | ||||||||
| Collaborators | Not Provided | ||||||||
| Investigators |
|
||||||||
| PRS Account | Sixth Affiliated Hospital, Sun Yat-sen University | ||||||||
| Verification Date | March 2019 | ||||||||
