Non-Invasive Colorectal Cancer Screening: An Overview

Abstract

Background: Colorectal cancer (CRC) follows a protracted stepwise progression, from benign adenomas to malignant adenocarcinomas. If detected early, 90% of deaths are preventable. However, CRC is asymptomatic in its early-stage and arises sporadically within the population. Therefore, CRC screening is a public health priority. Summary: Faecal immunochemical test (FIT) is gradually replacing guaiac faecal occult blood test and is now the most commonly used screening tool for CRC screening program globally. However, FIT is still limited by the haemoglobin degradation and the intermittent bleeding patterns, so that one in four CRC cases are still diagnosed in a late stage, leading to poor prognosis. A multi-target stool DNA test (Cologuard, a combination of NDRG4 and BMP3 DNA methylation, KRAS mutations, and haemoglobin) and a plasma SEPT9 DNA methylation test (Epi proColon) are non-invasive tools also approved by the US FDA, but those screening approaches are not cost-effective, and the detection accuracies remain unsatisfactory. In addition to the approved tests, faecal-/bloodbased microRNA and CRC-related gut microbiome screening markers are under development, with work ongoing to find the best combination of molecular biomarkers which maximise the screening sensitivity and specificity. Key Message: Maximising the detection accuracy with a cost-effective approach for non-invasive CRC screening is urgently needed to further reduce the incidence of CRC and associated mortality rates.

The Role of microRNAs in Development of Colitis-Associated Colorectal Cancer

“…Morilla et al [ 127 ] reported that the neural-network-developed algorithms utilized a total of nine miRNAs with five clinical features in IBD patients associated with anti-TNF monoclonal antibody therapy treatment response. Moreover, fecal-based miRNA screening has been investigated to find the pattern to detect colon diseases, including CRC [ 55 , 56 , 128 , 129 , 130 ] and IBD [ 131 , 132 ], in the early phases with non-invasive procedures. For example, stool miR-16, miR-21, miR-223 and miR-1246 expression resulted in being upregulated in active CD and UC patients compared to healthy controls and circulating miRNAs detection may further prevent the chance of Clostridioides difficile infection [ 133 ] in IBD patients.…”

The methylation level of TFAP2A is a potential diagnostic biomarker for retinoblastoma: an analytical validation study

“…Of them, testing for the screening of early colorectal cancer is among the most frequent uses of ctDNA methylation based assay. Highly methylated patterns are observed in BMP3, NDRG4 and SEPT9 in stool or blood samples from colorectal cancer patients ( Chen et al, 2019 ; Ahlquist et al, 2012 ; Tepus & Yau, 2020 ). The development of DNA methylation biomarkers is also emerging in other cancers, such as GSTP1 for prostate cancer ( Zhao et al, 2018 ), SHOX2 and RASSF1A for lung cancer methylation ( Zhang et al., 2017 ) and OTX1 for bladder cancer ( Van Kessel et al, 2016 ).…”

Fecal Multidimensional Assay for Non-Invasive Detection of Colorectal Cancer: Fecal Immunochemical Test, Stool DNA Mutation, Methylation, and Intestinal Bacteria Analysis

“…Moreover, there have been commercial stool DNA detection methods that have been used in clinical practice. However, head-to-head comparison with such commercial multitarget DNA test in feces (Cologuard™) was lack for screening for CRC ( 27 ). FIT test alone needs a small amount of stool, but patients had to collect more stools for our multidimensional assay and may feel inconvenient.…”