Cell-free nucleic acids as noninvasive biomarkers for colorectal cancer detection

Abstract

Cell-free nucleic acids (CFNA) have been reported by several authors in blood, stool, and urine of patients with colorectal cancer (CRC). These genetic biomarkers can be an indication of neoplastic colorectal epithelial cells, and can thus potentially be used as noninvasive tests for the detection of the disease in CRC patients and monitor their staging, without the need to use heavier and invasive tools. In a number of test-trials, these genetic tests have shown the advantage of non-invasiveness, making them well accepted by most of the patients, without major side effects. They have also shown a promising sensitivity and specificity in the detection of malignant and premalignant neoplasms. Moreover, costs for performing such tests are very low. Several studies reported and confirmed the proof of the principle for these genetic tests for screening, diagnosis, and prognosis; the main challenge of translating this approach from research to clinical laboratory is the validation from large and long-term randomized trials to prove sustainable high sensitivity and specificity. In this paper, we present a review on the noninvasive genetics biomarkers for CRC detection described in the literature and the challenges that can be encountered for validation processes.

Methylation of SFRP2 gene as a promising noninvasive biomarker using feces in colorectal cancer diagnosis: a systematic meta-analysis

“…Epigenetic silencing of tumor suppressor genes is an important mechanism in colorectal oncogenesis. Based on the advantages of DNA methylation, such as the convenience of detection, low cost, stability and non-invasive nature of methylation as a diagnostic biomarker, it could become a powerful biomarker for the early detection and diagnosis of colorectal cancer 4 . DNA methylation has previously been used as a biomarker in the detection of human diseases 5 6 .…”

Telomeric repeat-containing RNA (TERRA) constitutes a nucleoprotein component of extracellular inflammatory exosomes

“…Extracellular forms of repetitive DNA fragments, including telomeric DNA, have been shown to modulate inflammatory cytokine production (21). Furthermore, cell-free nucleic acids can be used as a biomarkers for various diseases, including autoimmunity and cancer (22). Cell-free nucleic acid has been identified in stable protein complexes, as well as encapsulated in microvesicles and exosomes (23)(24)(25).…”

Use of NCCN Guidelines, Other Guidelines, and Biomarkers for Colorectal Cancer Screening

“…32 Unfortunately, there are no Phase III biomarker studies of mutant or methylated DNA based biomarker assays for CRC detection in a screening setting at this time. 51 Furthermore and importantly, when considered in the context of other CRC and colon polyp screening methods, while a robust biomarker panel of methylated genes may be developed into a clinically accurate CRC screening method in the near future, the currently available blood based biomarker assays are not appropriate as colon polyp detection methods.…”