Study identifies fibroblast growth factor 18 as an ovarian cancer biomarker

Ovarian cancer is one of the leading causes of cancer-related death in women and is often not detected until the later stages of disease, which contributes to poor prognosis. Biomarkers that can be used for early diagnosis and outcome have been identified; however, many of these have not been evaluated at the biological and clinical levels.

In this issue of the Journal of Clinical Investigation, Michael Birrer and colleagues at Massachusetts General Hospital identify fibroblast growth factor 18 (FGF18) as a predictive marker for poor overall survival in ovarian cancer patients.

Overexpression of the gene encoding FGF18 was associated with enhanced tumor and expression of cancer promoting cytokines. These data indicate that further studies on the predictive potential FGF18 and its use as a therapeutic target in ovarian cancer are warranted.

More information: FGF18 as a prognostic and therapeutic biomarker in ovarian cancer, J Clin Invest. DOI: 10.1172/JCI70625

Abstract
High-throughput genomic technologies have identified biomarkers and potential therapeutic targets for ovarian cancer. Comprehensive functional validation studies of the biological and clinical implications of these biomarkers are needed to advance them toward clinical use. Amplification of chromosomal region 5q31–5q35.3 has been used to predict poor prognosis in patients with advanced stage, high-grade serous ovarian cancer. In this study, we further dissected this large amplicon and identified the overexpression of FGF18 as an independent predictive marker for poor clinical outcome in this patient population. Using cell culture and xenograft models, we show that FGF18 signaling promoted tumor progression by modulating the ovarian tumor aggressiveness and microenvironment. FGF18 controlled migration, invasion, and tumorigenicity of ovarian cancer cells through NF-?B activation, which increased the production of oncogenic cytokines and chemokines. This resulted in a tumor microenvironment characterized by enhanced angiogenesis and augmented tumor-associated macrophage infiltration and M2 polarization. Tumors from ovarian cancer patients had increased FGF18 expression levels with microvessel density and M2 macrophage infiltration, confirming our in vitro results. These findings demonstrate that FGF18 is important for a subset of ovarian cancers and may serve as a therapeutic target.

add to favorites email to friend print save as pdf

Related Stories

Biomarkers predict time to ovarian cancer recurrence

Aug 15, 2013

Ovarian cancer often remains undetected until it is at an advanced stage. Despite positive responses to initial treatment, many patients are at risk of tumor recurrence. A multitude of genetic markers have been implicated ...

Scientists find new gene linked to ovarian cancer

Sep 05, 2013

Cancer Research UK scientists have found a gene in mice that could protect against ovarian cancer and, if faulty, may increase the chance of developing the disease, according to research published in Nature.

Recommended for you

Mutations need help from aging tissue to cause leukemia

33 minutes ago

Why are older people at higher risk for developing cancer? Prevailing opinion holds that, over time, your body's cells accumulate DNA damage and that eventually this damage catches up with the body in a way ...

Specific oxidation regulates cellular functions

5 hours ago

For a long time, hydrogen peroxide has been considered as a dangerous metabolite that can damage cells through oxidation. This, however, is not its only role in the cell. Scientists from the German Cancer Research Center ...

New disease mechanism discovered in lymphoma

5 hours ago

Programmed cell death is a mechanism that causes defective and potentially harmful cells to destroy themselves. It serves a number of purposes in the body, including the prevention of malignant tumor growth. ...

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.