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      The Prognostic Value of Circulating Cell-Free DNA in Colorectal Cancer: A Meta-Analysis

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          Abstract

          Background: Circulating cell-free DNA (cfDNA) is a promising candidate biomarker for detection, monitoring and survival prediction of colorectal cancer (CRC). However, its prognostic significance for patients with CRC remains controversial. To derive a precise estimation of the prognostic significance of cfDNA, a meta-analysis was performed.

          Methods: We made a systematic search in data base of the Science Citation Index Embase and Pubmed for studies reporting prognostic data of cfDNA in CRC patients. The data of cfDNA on recurrences-free survival (RFS) and overall survival (OS) were extracted and measured in hazard rates (HRs) and 95% confident intervals (CIs). Subgroup analyses were carried out as well. Finally, the meta-analysis is accompanied with nine studies including 19 subunits.

          Results: The pooled HRs with 95% CIs revealed strong associations between cfDNA and RFS (HR [95%CI]=2.78[2.08-3.72], I 2=32.23%, n=7) along with OS (HR [95%CI]=3.03[2.51-3.66], I 2=29.24%, n=12) in patients with CRC. Entire subgroup analyses indicated strong prognostic value of cfDNA irrespective tumor stage, study size, tumor markers, detection methods and marker origin.

          Conclusions: All the results exhibits that appearance of cfDNA in blood is an indicator for adverse RFS and OS in CRC patients.

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          Most cited references45

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          Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints.

          Meta-analyses aim to provide a full and comprehensive summary of related studies which have addressed a similar question. When the studies involve time to event (survival-type) data the most appropriate statistics to use are the log hazard ratio and its variance. However, these are not always explicitly presented for each study. In this paper a number of methods of extracting estimates of these statistics in a variety of situations are presented. Use of these methods should improve the efficiency and reliability of meta-analyses of the published literature with survival-type endpoints.
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            Approaches to heterogeneity in meta-analysis.

            D Petitti (2001)
            This paper reviews publications from January 1999 to March 2001 on reproductive health topics that were self-identified as meta-analysis or were indexed as meta-analysis in MEDLINE. It sought to assess whether tests of statistical heterogeneity were done, whether the results were reported, and how a finding of significance for a test of statistical heterogeneity was handled and the results interpreted. The review identified some concerns. Tests of statistical heterogeneity were not done universally even though virtually all writers on the topic emphasize their importance. Even when done, results of these tests were not universally reported. Although the consensus appears to be that heterogeneity tests are conservative for meta-analysis of studies and a probability value of 0.10 is preferred, many meta-analyses used the conventional value of 0.05 without providing a reason. The rationale for the choice of a random or fixed effects model was not generally evident. The review also provided some positive models and some recommendations for assessing, reporting and exploring heterogeneity are made considering these models and the published recommendations of experts. Copyright 2001 John Wiley & Sons, Ltd.
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              Increased plasma DNA integrity in cancer patients.

              Tumor-released DNA in blood represents a promising biomarker for cancer detection. It has been postulated that tumor necrosis causes release of DNA of varying sizes, which contrasts apoptosis in normal tissue that releases smaller and more uniform DNA fragments. To test the hypothesis that increased DNA integrity, i.e., a longer DNA strand, is a tumor-associated marker in plasma, we determined the genomic DNA integrity index in plasma DNA using real-time PCR assays. A DNA integrity index and DNA concentration in plasma were determined in 61 patients with gynecological and breast cancers and 65 female patients without neoplastic diseases. We found that the area under the receiver-operating characteristic curve for DNA integrity index was 0.911 for cancer versus nonneoplastic patients. Given 100% specificity, the highest sensitivity achieved in detecting the cancer group was 62% (95% confidence interval = 0.50-0.74) at the index cutoff of 0.59. Fifty percent of stage I cancers had a DNA integrity index above this cutoff. All 11 patients with benign adnexal masses that clinically can be confused with malignant gynecological neoplasms demonstrated DNA integrity index < 0.59. Our findings suggest that increased DNA integrity in plasma DNA is associated with cancer, and measurement of DNA integrity may provide a simple and inexpensive measure for cancer detection.
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                Author and article information

                Journal
                J Cancer
                J Cancer
                jca
                Journal of Cancer
                Ivyspring International Publisher (Sydney )
                1837-9664
                2016
                4 June 2016
                : 7
                : 9
                : 1105-1113
                Affiliations
                1. Department of Gastrointestinal Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China;
                2. Department of Research Administration, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
                Author notes
                ✉ Corresponding authors: Hai-yan Ge, Email: ghy1333@ 123456easthospital.cn Zhen-Yu Zhang Email : zhangsurgery@ 123456qq.com . Department of Gastrointestinal Surgery, Shanghai East Hospital, Tongji University School of Medicine, Pudong New District, No. 150, Jimo Road, Shanghai, 200120, China. Tel: +86 21 38804518 Fax: +86 21 58798999.

                Competing Interests: The authors declare that they have no potential competing interests.

                Article
                jcav07p1105
                10.7150/jca.14801
                4911878
                27326254
                53c9007f-bc54-4e56-ab67-851e07b87d7e
                © Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions.
                History
                : 25 December 2015
                : 22 March 2016
                Categories
                Research Paper

                Oncology & Radiotherapy
                plasma dna,cell-free dna,colorectal cancer,prognosis,meta-analysis.
                Oncology & Radiotherapy
                plasma dna, cell-free dna, colorectal cancer, prognosis, meta-analysis.

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