CD70: A Potential Target in Breast Cancer?

ABSTRACT

CD70 is a co-stimulatory molecule involved in the immune response and also in cancer development and progression. Recent studies show that high CD70 expression in cancer cells may inhibit the anti-tumor response. Furthermore, CD70 expression has been reported as a predictive marker of resistance to chemotherapy in ovarian cancers. Some in vitro studies have shown that CD70 expression is epigenetically down-regulated through hypermethylation of its promoter during tumoral progression. This study evaluated the level of CD70 expression in surgical samples of breast invasive tumors and determined its correlation with CD70 promoter methylation. Twenty "luminal A" and 20 "basal-like" frozen samples from early breast tumors were retrospectively selected. CD70 expression was evaluated by quantitative real-time PCR. Total DNA was bisulfite-treated, and methylation levels of 5 consecutive CG sites present in the proximal region (-464, -421) of the promoter were assessed by pyrosequencing analysis. Statistical analyses were performed using the Mann-Whitney test. The median relative CD70 expression level was 0.37 and was significantly higher in the basal-like group (0.78 [0.24-31.7]) compared to the luminal A group (0.25 [0.03-1.83], p=0.0001). The median methylation level was 61%, with no significant difference between the basal-like (63%) and luminal A (58%) groups. No correlation was found between CD70 expression and CD70 methylation level. In this study, higher CD70 expression was observed in the basal-like group, but this expression was not related to promoter methylation. The higher expression in the poor-prognosis subgroup of patients makes CD70 a potential target for emerging anti-CD70 therapies.