Early detection of colorectal cancer: from conventional methods to novel biomarkers

Abstract

Purpose: Colorectal cancer (CRC) is one of the major health problems worldwide and is often diagnosed at late stage. There is growing body of evidence in early detection of this disease with novel screening modalities to reduce compliance and increase specificity of available methods. The aim of current review is to give an overview on currently available screening methods (e.g., fecal occult blood testing (FOBT), flexible sigmoidoscopy, and colonoscopy), with their own merits and disadvantages, and new genetic/epigenetic/protein markers, as novel screening modalities.

Result: There are several serum and fecal biomarkers that can predict CRC and polyps. Overall sensitivities for detection by fecal DNA markers ranged from 53 to 87%, while a panel of serum protein markers provides a sensitivity/specificity up to 85% for CRC. In particular, DNA methylation markers (e.g., SEPT9, SFRP2, and ALX4), circulating microRNAs (e.g., microRNA21), SNPs in microRNAs binding site (e.g., rs4596 located within a target region of the predicted miR-518a-5p and miR-527), protein markers (e.g., carcinoembryonic antigen, N-methyltransferase), or microsatellites instability in tumors with deficient mismatch repair of some genes are among the most interesting and promising biomarkers.

Conclusion: Increasing evidence supports the use of combined fecal and serum biomarkers with sigmoidoscopy and colonoscopy screening in order to maximize the benefits and reduce the number of false-positive tests and patients undergoing invasive methods, which in turn could overcome the limitations of the current screening methods for early detection of CRC and adenomas.

Keywords: Colorectal cancer; Fecal/serum biomarkers; Genomic/epigenetic biomarkers; microRNA.

Fig. 1

Stages of colorectal cancer, stage-specific gene mutation, and release of DNA from the malignant cells