Higher levels of cells originating in bone marrow may be useful in prognosis of liver cancer

A new study found that higher levels of specialized blood cells that originate in bone marrow may potentially be used as a prognostic marker in liver cancer.

A new study found that higher levels of specialized blood cells that originate in bone marrow may potentially be used as a prognostic marker in liver cancer. The study showed that elevated levels of endothelial progenitor cells (EPCs), the precursors to endothelial cells that are found in the lining of blood vessels, were found in patients with inoperable hepatocellular carcinoma (HCC) compared to those with tumors that could be treated surgically.

The results of this study appear in the October 2006 issue of Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD). Published by John Wiley & Sons, Inc., Hepatology is available online via Wiley InterScience at http://www.interscience.wiley.com/journal/hepatology.

HCC is a very aggressive form of cancer that is usually diagnosed when the disease is already at an advanced stage and therefore has a poor prognosis. HCC tumors have extensive new blood vessel formation, which requires the growth of endothelial cells. Recent studies have shown that proteins produced by the tumor may stimulate EPCs, which then travel to the tumor by way of the bloodstream. Although higher levels of EPCs have been associated with multiple myeloma (cancer of the plasma cells produced in bone marrow), their role in solid tumors has not been studied until now.

Led by Prof. Ronnie Poon of the Department of Surgery at the University of Hong Kong, researchers analyzed blood samples from 80 patients with HCC before they were treated and compared them with blood samples from 16 patients with cirrhosis and 14 patients who were healthy. Since EPCs are difficult to isolate and quantify, they measured EPC levels using a specific method that allowed them to culture blood cells and count the number of colonies (colony formation units or CFU) formed by endothelial cells. This enabled them to differentiate EPCs that originated in the bone marrow from endothelial cells that are found in normal tissues throughout the body. They also analyzed levels of vascular endothelial growth factor (VEGF) and interleukin-8 (IL8), two proteins that are thought to be involved in new blood vessel formation in tumors.

The results showed that the HCC patients had significantly higher CFU scores than the control patients, and that those with inoperable HCC had significantly higher CFU scores than those whose tumors could be treated surgically. "These findings could suggest a possible relationship between more aggressive tumor and higher circulating levels of EPCs," the authors state.

In addition, in the 17 patients who had surgery and were followed for at least one year, CFU scores prior to surgery were much higher in those who experienced recurrence within a year. Researchers also analyzed levels of alpha-fetoprotein (AFP), a specific biomarker of HCC, and found that patients with higher CFU scores had higher levels of AFP. Similarly, there was a correlation between both VEGF and IL8 levels and CFU scores. The authors note that "since both circulating levels of IL8 and VEGF have been reported to be highly associated with angiogenesis [new blood vessel formation] and prognosis of HCC, the finding in our study provides additional evidence for the possible role of EPCs in tumor angiogenesis."

"Taken together, our study suggests that EPCs may have a significant implication in HCC in terms of prognosis," the authors note. They suggest that further studies with more patients and longer follow-up times would be useful, as would further evaluations of known prognostic factors together with CFU and AFP levels. It would also be helpful to follow CFU scores over time in patients who undergo surgery for HCC to determine if EPC levels increase when and if tumors recur. The authors conclude: "Our data suggest that further studies are worthwhile to validate the prognostic value of circulating levels in HCC patients, and to explore possible therapeutic strategies against HCC by targeting bone marrow mobilization of EPCs."

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Article: "Significance of Circulating Endothilial Progenitor Cells in Hepatocellular Carcinoma," Joanna W. Y. Ho, Roberta W. C. Pang, Cecilia Lau, Chris K. Sun, Wan Ching Yu, Sheung Tat Fan, Ronnie T. P. Poon, Hepatology; October 2006 (DOI: 10.1002/hep.21353).


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