Study identifies fibroblast growth factor 18 as an ovarian cancer biomarker

September 9, 2013

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.

Explore further: Biomarkers predict time to ovarian cancer recurrence

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.

Related Stories

Biomarkers predict time to ovarian cancer recurrence

August 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 ...

Ovarian cancer cells hijack surrounding tissues to enhance tumor growth

September 4, 2012
Tumor growth is dependent on interactions between cancer cells and adjacent normal tissue, or stroma. Stromal cells can stimulate the growth of tumor cells; however it is unclear if tumor cells can influence the stroma.

Resistance is futile: Researchers identify gene that mediates cisplatin resistance in ovarian cancer

April 15, 2013
Platinum compounds, such as cisplatin and carboplatin, induce DNA cross-linking, prohibiting DNA synthesis and repair in rapidly dividing cells. They are first line therapeutics in the treatment of many solid tumors, but ...

Team finds markers related to ovarian cancer survival and recurrence

April 30, 2013
(Medical Xpress)—Researchers at the University of Illinois have identified biomarkers that can be used to determine ovarian cancer survival and recurrence, and have shown how these biomarkers interact with each other to ...

Scientists find new gene linked to ovarian cancer

September 5, 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.

Dogs help sniff out ovarian cancer in Pa. study

August 9, 2013
Researchers in Philadelphia have begun an ovarian cancer detection study that relies on dogs' keen sense of smell.

Recommended for you

Anti-cancer chemotherapeutic agent inhibits glioblastoma growth and radiation resistance

July 24, 2017
Glioblastoma is a primary brain tumor with dismal survival rates, even after treatment with surgery, chemotherapy and radiation. A small subpopulation of tumor cells—glioma stem cells—is responsible for glioblastoma's ...

New therapeutic approach for difficult-to-treat subtype of ovarian cancer identified

July 24, 2017
A potential new therapeutic strategy for a difficult-to-treat form of ovarian cancer has been discovered by Wistar scientists. The findings were published online in Nature Cell Biology.

Immune cells the missing ingredient in new bladder cancer treatment

July 24, 2017
New research offers a possible explanation for why a new type of cancer treatment hasn't been working as expected against bladder cancer.

Shooting the achilles heel of nervous system cancers

July 20, 2017
Virtually all cancer treatments used today also damage normal cells, causing the toxic side effects associated with cancer treatment. A cooperative research team led by researchers at Dartmouth's Norris Cotton Cancer Center ...

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

Immune-cell numbers predict response to combination immunotherapy in melanoma

July 20, 2017
Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco ...

0 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.