Abstract
The application of circulating tumor DNA(ctDNA) represents a non-invasive method for tumor detection. Its prognostic significance in patients with colorectal cancer is controversial. We performed a systematic review of data from published studies to assess the prognostic values of ctDNA in patients with colorectal cancer. We searched Medline, Embase, Web of Science, the Cochrane Library, and Scopus databases to identify eligible studies reporting disease-free survival (DFS) and overall survival (OS) stratified by ctDNA prior to December 6, 2016. We evaluated the quality and design of these studies. A total of 22 studies were eligible for systematic review. Among them, 11 studies investigated the prognostic value of ctDNA on disease-free survival (DFS). Seven of 11 studies showed that ctDNA was an independent variable to estimate the probability of DFS by multivariate analyses. Thirteen studies assessed the relationship between ctDNA and overall survival (OS). Eight of 13 studies showed that ctDNA was an independent predictor of worse OS through the use of multivariate analyses. This analysis provides evidence that ctDNA may be a prognostic biomarker, negatively correlated with the survival of patients with colorectal cancer.
Highlights
Circulating free DNA with tumor-specific alterations is found in serum or plasma and represents a small fraction of the total circulating free DNA
We used combinations of the following search terms: “Colonic Neoplasm,” “Neoplasm, Colonic,” “Neoplasms, Colonic,” “Colon Neoplasms,” “Colon Neoplasm,” “Neoplasm, Colon,” “Neoplasms, Colon,” “Cancer of Colon,” “Colon Cancers,” “Cancer of the Colon,” “Colonic Cancer,” “Cancer, Colonic,” “Cancers, Colonic,” “Colonic Cancers,” “Colon Cancer,” “Cancer, Colon,” “Cancers, Colon,” “colonic,” “colorectal disease,” “rectal neoplasms,” “colorectal polyps,” “sigmoid neoplasms,” “colorectal adenoma,” “circulating tumor DNA,” “Circulating free DNA with tumor-specific alterations (ctDNA),” “cell free DNA,” “serum DNA,” “plasma DNA,” “circulating DNA,” “free DNA,” “prognosis,” “survival,” “prognostic,” and “predictive.” No restrictions were placed on the search, and relevant MeSH (Medline) or Emtree (Embase) terms were used where possible
To the best of our knowledge, this is the first systematic review to explore the relationship between ctDNA status and prognosis in patients with colorectal cancer (CRC)
Summary
Circulating free DNA with tumor-specific alterations (ctDNA) is found in serum or plasma and represents a small fraction of the total circulating free DNA. Some specific genetic alterations detected in ctDNA are driver alterations that are responsible for the initiation and progression of human cancers. Those alterations play broad roles in vivo, such as affecting genomic surveillance mechanisms and reducing cells’ ability to detect and/or repair DNA damage, which increases susceptibility to DNA damage by exogenous and endogenous carcinogens [4]. Epigenetic alterations, such as methylation of CpG islands in promoter
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