Clinical

ApoD underexpression associated with poor hepatocellular carcinoma outcome

Last Updated: 2005-07-25 15:15:02 -0400 (Reuters Health)

By Will Boggs, MD

NEW YORK (Reuters Health) - Underexpression of the putative tumor suppressor gene apolipoprotein D (ApoD) is associated with worse outcomes in patients with hepatocellular carcinoma (HCC), according to a report in the August 10th International Journal of Cancer.

"Our findings may provide a novel therapeutic strategy for inducing the cellular differentiation or preventing the cellular dedifferentiation of HCC" by increasing the expression of ApoD," Dr. Masaki Mori from Kyushu University, Beppu, Japan told Reuters Health.

Dr. Mori and colleagues investigated whether the expression of ApoD mRNA was involved in the clinicopathological features of HCC in 70 patients who underwent surgery to resect their tumors.

ApoD expression was significantly lower in HCC tumor tissue than in the corresponding nontumor tissue, the authors report.

Expression of ApoD was highest in well-differentiated HCC, lower in moderately differentiated HCC, and lowest in poorly differentiated HCC, the report indicates.

Patients whose tumors had low expression of ApoD had a significantly lower 4-year survival rate (49.2%) than did patients whose tumors had high expression of ApoD (66.4%), the researchers note.

Additional experiments demonstrated that ApoD underexpression likely resulted from inactivation of the ApoD promoter region by hypermethylation.

"In patients with hematopoietic neoplasms, an induction therapy with some effective agents is considered as one of therapeutic strategies," Dr. Mori explained. "However, in cases of solid cancers, the therapy has not been considered practically. Our study may provide the possibility to perform such therapy even in patients with solid cancer."

"Induction of ApoD expression using demethylating reagents may control the tumor aggressiveness associated with less cellular differentiation, and this action may consequently improve the outcome of patients," the investigators suggest.

"We would like to investigate the role of ApoD and retinoic acid during the process of hepatocarcinogenesis," Dr. Mori added.

Int J Cancer 2005;116:105-109.