New molecular diagnosis and screening methods for colorectal cancer using fecal protein, DNA and RNA

Abstract

Several screening methods for reducing the mortality rate of colorectal cancer (CRC) have been reported in recent decades. Fecal occult blood tests (FOBTs) are widely used for CRC screening and immunochemical FOBTs perform better than guaiac FOBTs; however, the sensitivity and specificity of immunochemical FOBTs remain unsatisfactory. To resolve this problem, novel fecal molecular methods based on fecal protein, DNA and RNA analyses have been developed. Regarding fecal proteins, several marker proteins indicating intestinal bleeding and cancer cell-specific proteins have been investigated. Regarding fecal DNA, numerous gene mutation and gene methylation analyses have been reported. Consequently, fecal DNA analysis was recommended as a CRC screening method in 2008. In addition, gene expression analyses of CRC-specific genes and miRNAs in fecal RNA have been investigated over the last decade. This review article summarizes molecular methods using fecal samples for CRC screening, focusing on reports within the last 5 years.

Keywords::

• colorectal cancer
• cancer screening
• fecal DNA
• fecal protein
• fecal RNA
• molecular diagnostics

Acknowledgements

The authors thank Kaoru Shiina for her secretarial assistance.

Financial & competing interests disclosure

Y Koga was supported by a Grant-in-Aid for the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO) of Japan and Young Scientists (B) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. Y Matsumura was supported by the Innovation Promotion Program from the New Energy and Industrial Technology Development Organization (NEDO) of Japan; Japan Society for the Promotion of Science (JSPS) through the ‘Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program)’, initiated by the Council for Science and Technology Policy (CSTP) and National Cancer Center Research and Development Fund. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Immunochemical fecal occult blood tests (iFOBTs) detect colorectal cancer (CRC) better than chemical or guaiac fecal occult blood tests.

• There are no known protein markers for sensitively detecting intestinal bleeding comparable to hemoglobin (iFOBT).

• Fecal tumor M2-PK is well studied; however, more evidence is needed regarding its efficacy.

• In the last decade, fecal DNA-based tests, especially fecal methylated DNA analyses, have been the most studied tests worldwide.

• The sensitivity and specificity of next-generation stool DNA tests for detecting CRC are 85% and 89%, respectively.

• Fecal RNA-based tests have many technical problems.

• miRNAs are relatively stable in fecal samples; further examination aiming to identify novel fecal miRNA markers for colorectal cancer screening is necessary.

• Some healthy subjects have false-positive results while some colorectal cancer patients have false-negative results according to iFOBTs; further investigation of novel fecal molecular diagnostics is required in the next decade.