Molecular Minutes

Colon Cancer Biomarkers Guide

Posted by Applied Biological Materials (abm) on March 17, 2020

Colon Cancer Biomarkers Guide

 

Did you know that colon cancer is more common in developed countries? Around 65% of cases are found in these regions.13 In fact, colorectal cancer is the third most common cancer in the world and is diagnosed in 1 out of every 10 diagnoses.1 As such, it is a major focus in cancer research.

Tumour markers are generally proteins expressed in normal/healthy and cancer cells, but are expressed at an abnormal level in cancer cells.2 Thus, tumour markers serve as a way to diagnose and detect some types of cancers, with immunohistochemistry (IHC) being an important tool for identifying different colon cancers.

In this article, we’ll discuss the gene expression landscape of colon cancer and identify key markers for this disease.

  1. Overexpressed genes
  2. Underexpressed genes
  3. Cell cycle markers
  4. Cell surface markers
  5. Summary of colon cancer markers
                     

1. Overexpressed proteins in colon cancer

A common characteristic in cancer cells is uncontrolled expression of key proteins involved in cell signaling and proliferation. There is a subset of overexpressed genes that distinctly characterize cancer as colon cancer.3 For example, the following genes are overexpressed:

  • EPCAM: The EPCAM gene encodes for the epithelial cell adhesion molecule, a protein that is overexpressed in colon cancer. This transmembrane glycoprotein has oncogenic potential as it promotes the upregulation of tumor growth associated genes such as c-myc and e-fabp.4,5


Recommended:Recommended IHC Antibody:
SensiStain™Anti-EpCAM Antibody

 

  • p504s: The AMACR gene (also known as p504s) encodes for the Alpha-methylacyl-CoA racemase enzyme that is involved in the metabolism of fatty acids. p504s is another key gene that is overexpressed in colon cancer cells, however its precise role is still unclear.6


Recommended:Recommended IHC Antibody:
SensiStain™Anti-p504s Antibody

 

HY000206 p504s SensiStain IHC Antibody on Colon Tissue

 

2. Underexpressed proteins in colon cancer

Underexpression of genes involved in transcriptional regulation are common indicators of a cancerous cell. For example, for colon cancers, the following genes are underexpressed:

  • p27: p27 is a protein that negatively regulates the cell cycle by acting as a CDK (cyclin-dependent kinase) inhibitor. Low levels of p27 are highly correlated with colon cancer7, as cyclin-dependent kinase activity and cell proliferation increase.


Recommended:Recommended IHC Antibody:
SensiStain™Anti-p27 Antibody


  • PAX8: The PAX8 gene encodes for the paired box gene 8 protein which is a transcription factor that plays an important role in organogenesis, regulating cell cycle genes such as CCNB1 and CCNB2. PAX8 expression is completely absent in colon cancer and many other types of cancers8 , making it a novel marker for differentiating between different cancers.


Recommended:Recommended IHC Antibody:
SensiStain™Anti-PAX8 Antibody

 

HY000210 PAX8 SensiStain IHC Antibody on Endometrium Tissue

 

3. Cell cycle markers for colon cancer

Abnormal expression of cell cycle proteins is commonly associated with cancers due to their high influence on proliferation and downstream effects on the cell. For example:

  • PMS2 and MLH1: The PMS2 gene and the MLH1 gene encode for two notable enzymes involved in DNA mismatch repair9 and are deficient in colon cancer cells. Cells with deficient PMS2 and MLH1 accumulate DNA replication errors, resulting in microsatellite instability (areas of the DNA that are highly susceptible to mutations). These proteins also interact with the tumor protein, p53, to arrest the cell cycle when DNA is damaged and initiate DNA repair or apoptosis.


Recommended:Recommended IHC Antibody:
SensiStain™Anti-PMS2 Antibody
SensiStain™Anti-MLH1 Antibody

 

HY000217 PMS2 SensiStain IHC Antibody on Cervix Tissue

 

4. Cell surface markers for colon cancer

A number of cell surface antigens also have altered expressions in cancer cells. For example:

  • MUC1: The MUC1 gene encodes for Mucin 1, a glycoprotein that lines epithelial cells in several organs, binding to pathogens and preventing them from entering the cell. In colon cancer10 and other cancer cells, Mucin 1 is overexpressed at the cell surface, inhibiting the ability of drugs and immune cells to bind and destroy a cancer cell. High levels of Mucin 1 also promote excessive binding of growth factors, resulting in increased cancer cell growth. In addition, MUC1 immunohistochemistry is a method that can distinguish mesothelioma from adenocarcinomas like colon cancer.12


Recommended:Recommended IHC Antibody:
SensiStain™Anti-MUC1 Antibody

 

  • TAG-72: This mucin-like protein is also overexpressed on the surface of many cancer cells, including colon cancer cells11.


Recommended:Recommended IHC Antibody:
SensiStain™Anti-TAG-72 Antibody

 

HY000242 TAG-72 SensiStain IHC Antibody on Ovary Tissue

 

5. Summary of Markers for Colon Cancer

Here at abm we have a large collection of SensiStain™ antibodies for colon cancer research. A summary of the markers and their corresponding SensiStain™ Antibody are listed below:

Antigen Antibody
EpCAM Sensistain™ Anti-EpCAM Antibody
p504s Sensistain™ Anti-p504s Antibody
p27 Sensistain™ Anti-p27 Antibody
PAX8 Sensistain™ Anti-PAX8 Antibody
p53 Sensistain™ Anti-p53 Antibody
MUC1 Sensistain™ Anti-MUC1 Antibody
TAG-72 Sensistain™ Anti-TAG-72 Antibody
MLH1 Sensistain™ Anti-MLH1 Antibody
PMS2 Sensistain™ Anti-PMS2 Antibody

 

Have questions or need help with your project? Contact our Technical Support team at technical@abmgood.com or leave us a comment below!

Histology Catalog Banner

 

References:

  1. Forman D, Ferlay J (2014). "Chapter 1.1: The global and regional burden of cancer". In Stewart BW, Wild CP (eds.). World Cancer Report. the International Agency for Research on Cancer, World Health Organization. pp. 16–53. ISBN 978-92-832-0443-5.

  2. https://labtestsonline.org/tests/tumor-markers

  3. Uhlen M, Zhang C, Lee S, Sjöstedt E, Fagerberg L, Bidkhori G, Benfeitas R, Arif M, Liu Z, Edfors F, Sanli K, von Feilitzen K, Oksvold P, Lundberg E, Hober S, Nilsson P, Mattsson J, Schwenk JM, Brunnström H, Glimelius B, Sjöblom T, Edqvist PH, Djureinovic D, Micke P, Lindskog C, Mardinoglu A, Ponten F (August 2017). "A pathology atlas of the human cancer transcriptome". Science. 357 (6352): eaan2507. 

  4. Maetzel, Dorothea; et al. (2009). "Nuclear signalling by tumour-associated antigen EpCAM". Nature Cell Biology. 11 (2): 162–71. doi:10.1038/ncb1824. PMID 19136966

  5. Dasgeb, Bahar; Mohammadi, Tarana M; Mehregan, Darius R (2013). "Use of Ber-EP4 and Epithelial Specific Antigen to Differentiate Clinical Simulators of Basal Cell Carcinoma". Biomarkers in Cancer. 5: BIC.S11856. doi:10.4137/BIC.S11856. ISSN 1179-299X

  6.  Lloyd MD, Darley DJ, Wierzbicki AS, Threadgill MD (Mar 2008). "Alpha-methylacyl-CoA racemase--an 'obscure' metabolic enzyme takes centre stage". The FEBS Journal. 275 (6): 1089–102. doi:10.1111/j.1742-4658.2008.06290.x. PMID 18279392

  7. Nakayama KI, Nakayama K (May 2006). "Ubiquitin ligases: cell-cycle control and cancer". Nat. Rev. Cancer. 6 (5): 369–81. doi:10.1038/nrc1881. PMID 16633365.

  8. https://www.ncbi.nlm.nih.gov/pubmed/21285870

  9. van Oers JM, Roa S, Werling U, Liu Y, Genschel J, Hou H, Sellers RS, Modrich P, Scharff MD, Edelmann W (12 July 2010). "PMS2 endonuclease activity has distinct biological functions and is essential for genome maintenance". Proc. Natl. Acad. Sci. U.S.A. 107 (30): 13384–9. doi:10.1073/pnas.1008589107. PMC 2922181. PMID 20624957.

  10.  Gendler SJ (July 2001). "MUC1, the renaissance molecule". J. Mammary Gland Biol Neoplasia. 6 (3): 339–353. doi:10.1023/A:1011379725811. PMID 11547902.

  11.  TAG-72 antigen entry in the public domain NCI Dictionary of Cancer Terms

  12. Cooper K; Leong AS-Y; Leong JW-M (2003). Manual of diagnostic antibodies for immunohistology. London: Greenwich Medical Media. pp. 205–206. ISBN 978-1-84110-100-2.

  13.  Bosman, Frank T. (2014). "Chapter 5.5: Colorectal Cancer". In Stewart, Bernard W.; Wild, Christopher P (eds.). World Cancer Report. the International Agency for Research on Cancer, World Health Organization. pp. 392–402. ISBN 978-92-832-0443-5.

 

Topics: Biomarkers Guide, Colon Cancer, Histology

Molecular Minutes

Educational resources for life scientists and interviews with scientists/science communicators in the field.

For more in-depth articles, check out our knowledge base, which covers topics such as CRISPR, Next Generation Sequencing, PCR, Cell Culture, and more.

Blog managed by Applied Biological Materials (abm). 

Subscribe to Email Updates

Recent Posts