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Exploring Colon Cancer with Prestige Antibodies® Powered by Atlas Antibodies

By: Charlotta Agaton, Ph.D.; Ylva Almqvist, Ph.D., Biowire Spring 2012, 29–30

Biowire Spring 2012 — Live Cell Imaging of Signaling Pathways

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Colorectal Cancer

Colorectal cancer (CRC) is one of the most common types of cancer. Each year, approximately one million new cases are detected, and approximately 600,000 deaths can be attributed to this disease worldwide. Today, surgery is the only curative treatment for colorectal cancer, but adjuvant treatment may significantly improve patient survival. For adjuvant treatment to be successful, however, it is important to correctly identify patients who will benefit from treatment. Since adjuvant treatment is recommended for patients with stage III and high-risk stage II disease, it is of utmost importance to find biomarkers that can separate high-risk disease from low-risk disease.

Finding a Biomarker in the Human Protein Atlas

Podocalyxin (PODXL) is a transmembrane protein that is involved in cell-cell interaction. In normal tissue, the protein is expressed in the kidney glomeruli where it may play an anti-adhesive role in the kidney podocytes (Figure 1). The PODXL protein is overexpressed in several types of cancer, e.g., breast, prostate, and testicular cancer.

PODXL was originally identified as a potentially interesting testicular cancer biomarker on the Human Protein Atlas1,2. When further investigated in other selected cancer forms, PODXL was later found to be particularly interesting as a prognostic biomarker in colorectal cancer. High PODXL expression was shown to be an independent predictor of poor prognosis3.

Immunohistochemical staining using Anti-PODXL in normal human kidney

Figure 1. Immunohistochemical staining using Anti-PODXL (HPA002110) in normal human kidney shows strong membranous staining of cells in glomeruli on the Human Protein Atlas.

PODXL

The Malmö Diet and Cancer Study (MDCS) is a prospective cohort study designed with the aim of investigating dietary factors that might lead to an increased risk for certain types of cancer. Between 1991 and 1996 there were 28,098 persons enrolled in this ongoing study. By the end of 2008, 626 cases of CRC had been registered. From these CRC cases, a tissue microarray was constructed where PODXL expression could be evaluated based on immunohistochemistry in 536 tumors3.

Half of the tumors showed no PODXL staining, 37% showed weak or moderate staining, and 13% showed strong PODXL staining. See Figure 2 for IHC images of tumors showing strong membranous PODXL staining. A clear correlation could be found beween high PODXL expression and advanced T-stage, N-stage, M-stage, low differentiation grade, and presence of vascular invasion. There was no association between PODXL expression and age, gender, or tumor location.

Immunohistochemical staining of PODXL protein in colorectal tumors

Figure 2. Immunohistochemical staining (using HPA002110) of PODXL protein in colorectal tumors with an increasing proportion of cells showing strong membranous staining in the tumor samples from left to right.

A high PODXL expression correlated with a shorter colorectal cancerspecific survival (CCSS) (Figure 3A), indicating that PODXL is a prognostic biomarker for identifying patients with a poor prognosis.

Patients with tumors expressing high levels of PODXL who were treated with adjuvant chemotherapy (CT) had similar survival to patients with PODXL-low tumors. Untreated patients with PODXL-high tumors had shorter survival than all the other patient groups (Figure 3B). These results suggest patients with tumors expressing high levels of PODXL would benefit from adjuvant chemotherapy.

Kaplan-Meier analysis of colorectal cancer-specific survival

Figure 3. A) Kaplan-Meier analysis of colorectal cancer-specific survival of patients with tumors expressing no, weak/moderate, or high levels of PODXL protein. B) Kaplan-Meier analysis of colorectal cancer-specific survival, where patients were divided into groups according to whether they received adjuvant chemotherapy (CT) or not, as well as the level of tumor PODXL expression (high or low).

Summary

  • There is a great need today for novel biomarkers capable of distinguishing between different types, stages, and forms of colorectal cancer.
  • Potential cancer biomarkers can be identified on the Human Protein Atlas web portal (proteinatlas.org).
  • By the use of Prestige Antibodies®, PODXL was found to be a prognostic biomarker in colorectal cancer, with high PODXL expression being an independent predictor of poor prognosis.
  • Analyzing PODXL expression could stratify patients into those that should receive chemotherapy and those that may be spared adjuvant treatment.

Click here for more information on Prestige Antibodies.

Materials

     

 References

  1. Uhlén M, Oksvold P, Fagerberg L, et al. Towards a knowledge-based Human Protein Atlas. Nat Biotechnol. 2010;28(12):1248–50.
  2. Pontén F, Jirström K, Uhlén M. The Human Protein Atlas — a tool for pathology. J Pathology. 2008;216(4):387–93.
  3. Larsson A, Johansson ME, Wangefjord S, et al. Overexpression of podocalyxin-like protein is an independent factor of poor prognosis in colorectal cancer. Br J Cancer. 2011;105(5):666–72.

 

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