Fibroblast growth factor 18 (FGF18) has been identified as a predictive marker for poor overall survival in patients with ovarian cancer in a new study. When the gene encoding FGF18 was overexpressed, tumor blood vessel formation and expression of cancer-promoting cytokines were enhanced.
Ovarian cancer is one of the leading causes of cancer-related death in women. It is often not detected until the later stages of the disease, which contributes to poor prognosis. The long-term survival rate for patients diagnosed with advanced disease remains at 30%.
Michael Birrer, MD, PhD, and colleagues at Massachusetts General Hospital in Boston investigated the role of FGF18 in ovarian cancer as both a prognostic and therapeutic biomarker. When high-grade tumors were compared with benign cysts, FGF18 was overexpressed in about 50% of the high-grade tumors. The study was published in The Journal of Clinical Investigation (2013; doi:10.1172/JCI70625).
The research team found that FGF18 facilitates the progression of ovarian cancer by regulating both tumor cells and the tumor microenvironment. Further, FGF18 may contribute to the aberrant signaling pathways that are responsible for the cancer. Over 50% of ovarian cancers have seven signaling pathways activated, and three of these overlap with potential downstream signals from FGF18.
Analysis of mRNA and protein expression found that FGF18 was upregulated in ovarian tumors compared with normal ovary tissues and that overall survival was poor for patients with increased expression of FGF18 mRNA and protein. FGF18 affected both angiogenesis (the growth of new blood vessels) and tumor-associated macrophages both in the laboratory and in samples from patients with ovarian cancer. Both cell culture and xenograft models found that FGF18 signaling modulated ovarian tumor aggressiveness and the microenvironment.
The roles of FGF18 in microvessel density, tumor-associated macrophage infiltration, and overall patient survival validate its value for prognosis. Further, the research team suggested that FGF18 may be a potential therapeutic target.