The importance of stool DNA methylation in colorectal cancer diagnosis: A meta-analysis

Abstract

A large number of tumor-related methylated genes have been suggested to be of diagnostic and prognostic values for CRC when analyzed in patients' stool samples; however, reported sensitivities and specificities have been inconsistent and widely varied. This meta-analysis was conducted to assess the detection accuracy of stool DNA methylation assay in CRC, early stages of CRC (advanced adenoma, non-advanced adenomas) and hyperplastic polyps, separately. We searched MEDLINE, Web of Science, Scopus and Google Scholar databases until May 1, 2016. From 469 publications obtained in the initial literature search, 38 studies were included in the final analysis involving 4867 individuals. The true positive, false positive, true negative and false negative of a stool-based DNA methylation biomarker using all single-gene tests considering a certain gene; regardless of a specific gene were pooled and studied in different categories. The sensitivity of different genes in detecting different stages of CRC ranged from 0% to 100% and the specificities ranged from 73% to 100%. Our results elucidated that SFRP1 and SFRP2 methylation possessed promising accuracy for detection of not only CRC (DOR: 31.67; 95%CI, 12.31–81.49 and DOR: 35.36; 95%CI, 18.71–66.84, respectively) but also the early stages of cancer, adenoma (DOR: 19.72; 95%CI, 6.68–58.25 and DOR: 13.20; 95%CI, 6.01–28.00, respectively). Besides, NDRG4 could be also considered as a significant diagnostic marker gene in CRC (DOR: 24.37; 95%CI, 10.11–58.73) and VIM in adenoma (DOR: 15.21; 95%CI, 2.72–85.10). In conclusion, stool DNA hypermethylation assay based on the candidate genes SFRP1, SFRP2, NDRG4 and VIM could offer potential diagnostic value for CRC based on the findings of this meta-analysis.

DNA methylation biomarkers in stool for early screening of colorectal cancer

“…In the past few years, significant progress has been made on the sensitivity and specificity of biomarker in stool from CRC patients, demonstrating it as a viable option for CRC screening 18-22. Ahlqist and colleagues reported that during the progression of CRC tumorigenesis, biomarkers release into the stool earlier than into blood 23. Thus, aberrant methylated biomarker screening in stool may help with CRC prevention and early detection.…”

Hypermethylation of Corticotropin Releasing Hormone Receptor-2 Gene in Ulcerative Colitis Associated Colorectal Cancer

“…Assaying molecular markers in stool samples is a promising noninvasive method for screening CRC (42)(43)(44)(45)(46). A recent systematic review demonstrated the eligibility and feasibility of DNA methylation as a noninvasive biomarker in stool samples for the diagnosis of CRC and adenoma (44).…”

Towards precision medicine: advances in 5‐hydroxymethylcytosine cancer biomarker discovery in liquid biopsy

“…However, the invasive nature of colonoscopy leads to poor patient compliance. Stool and blood DNA methylation assays based on candidate genes show great diagnostic and prognostic values, but the sensitivities and specificities of the assays vary and are usually inconsistent [78]. In a Chinese cohort study evaluating cfDNA-derived 5hmC analysis in 80 colorectal cancer patients and 90 healthy individuals [45], a total of 989 differentially methylated 5hmC loci in gene bodies were selected as biomarkers to train the machine learning algorithm for cancer classification.…”