Biomarkers in Colorectal Cancer Screening

Colorectal cancer is the second most frequent cause of death by cancer. Current gold standard screening tools are invasive, expensive, and require a lot of preparation, which result in decreased patient compliance. Screening modalities that are less invasive, have high sensitivity and specificity, inexpensive, and more accepted by the general population than the current gold standard screening tools may potentially prevent the deaths caused by colorectal cancer. Noninvasive stool tests like fecal occult blood test and fecal immunohistochemical test have become widely used in detecting hemoglobin in stool. Some of these biomarkers have shown favorable results to detecting adenomas and early stage colorectal cancer diagnosis. Furthermore, the evolution of biomarkers is becoming more promising for the early diagnosis of colorectal cancer. This article will discuss the advances of biomarkers in stool, serum, and urine assays that enable early detection of colorectal cancer. The recent advances in stool DNA testing have allowed for high detection rates of colorectal cancer and advanced adenomas. Stool nucleic acids include the genes that are involved in chromosomal instability, which make up 50-80% of those involved in non invasive testing and microsatellite instability, which make up 10-15%. The different categories of stool DNA testing that will be discussed in this article include nucleic acid testing including multitarget stool DNA testing, epigenetic biomarkers like DNA methylation, hypermethylation, and hypomethylation markers, genetic biomarkers, long DNA, microRNA, fecal protein assay biomarkers. Serum markers that will be discussed include nonenzymatic tumor markers: CEA, CA 19-9, TPS, TAG72 and enzymatic tumor marker, which include neutrophil elastase, cathepsin D and lysosomal exoglycosidases, N methyltranserase, TIMP1, among others. Several of the urinary markers are also introduced. We also review other noninvasive technologies that are being investigated that may allow for highly accurate metholdology for cancer screening. Currently, the following noninvasive biomarkers are commercially available: plasma septin 9, CEA, CA19-9, TPS, TAG72, and stool Cologuard test which consists of KRAS mutations, aberrant NDRG4 and BMP3 methylation, and β-actin, plus a hemoglobin immunoassay. Noninvasive screening of colorectal cancer allows for increased patient acceptance and compliance, and is making a lot of progress since its inception. Although there have been promising advances in the use of biomarkers for colorectal cancer detection, large, long term prospective-multicenter clinical studies are necessary to determine if these tests have high enough sensitivity and specificity to be first line tests to diagnose colorectal cancer.