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Ovarian Cancer Discovery Deepens Knowledge of Survival Outcomes

10-Gene Biomarker Identified As a Tool in Evaluating Diagnosis, Potential Response to Treatment and Overall Prognosis

Los Angeles - Dec. 9, 2013 - Researchers in the Women's Cancer Program at Cedars-Sinai's Samuel Oschin Comprehensive Cancer Institute have identified a series of 10 genes that may signify a trifecta of benefits for women diagnosed with ovarian cancer and ultimately reflect improved survival outcomes.

The research, led by Dong-Joo (Ellen) Cheon, PhD, found that the 10-gene biomarker panel may identify the aggressiveness of a patient's disease, help predict survival outcomes and result in novel therapeutic strategies tailored to patients with the most adverse survival outcomes.

When a patient's tumor is identified as having elevated levels of these 10 specific genes, doctors may be able to better predict which treatments would be most effective, said Cheon, whose research was published in Clinical Cancer Research.

That is an important advance because ovarian cancer is the most lethal gynecologic cancer and is often diagnosed in later, more aggressive stages, resulting in poor prognosis and survival. These outcomes differ due to development of tumors that become resistant to chemotherapy. By identifying chemo-resistant tumors and identifying the risk of poor survival outcomes during the diagnostic process, investigators hope to extend lives and improve treatment responses for women with ovarian cancer.

"The ultimate goal is to use the 10-gene biomarker panel to develop a diagnostic kit that will identify patients with the most adverse outcome and provide targeted therapeutic strategies," said Cheon. "Among the biomarkers identified, the gene COL11A1 was shown to be the most abundantly expressed in ovarian cancer progression. But when we blocked expression of COL11A1 in murine cancer cells, tumor growth and spread was significantly reduced."

The 10-gene biomarker panel revealed another promising benefit. The 10 genes associated with the panel all share one common biological process — the formation of a collagen matrix around cancerous cells. This thick, collagen-rich matrix can protect cancer cells from the lethal effect of chemotherapy and serve as an incubator for increasingly aggressive cancer cells. Understanding how this collagen-rich environment may contribute to aggressive tumor cell behavior may ultimately lead to more efficient therapies.

"This data, based on the analysis of nearly 800 ovarian cancer patients, suggests that patients who have elevated levels of genes associated with the biomarker panel have shorter survival and more aggressive forms of disease," said Sandra Orsulic, PhD, senior author of this study, director of women's cancer biology in the Women's Cancer Program and associate professor in the Department of Obstetrics and Gynecology. "These findings indicate that even though patients present with the same disease stage at diagnosis, their survival outcomes differ."

The findings suggest that the 10-gene signature may have both predictive value and biological relevance that may be useful in treating patients.

Cedars-Sinai collaborators include Beth Y. Karlan, MD, director of the Women's Cancer Program, director in the Division of Gynecologic Oncology in the Department of Obstetrics and Gynecology, director of the Gilda Radner Hereditary Cancer Program and the Board of Governors Chair in Gynecologic Oncology; Yunguang Tong, PhD, assistant professor in the Department of Medicine; Dror Berel, senior biostatistician in the Biostatistics and Bioinformatics Research Core  Xiaojiang Cui, PhD, associate professor in the Women's Cancer Program; Jessica A. Beach, a graduate student in the Graduate Program in Biomedical Sciences and Translational Medicine; Mourad Tighiouart, PhD, associate director in the department of Biostatistics and Bioinformatics; and Ann E. Walts, MD, a research pathologist in the Samuel Oschin Comprehensive Cancer Institute.

Myung-Shin Sim, DrPH, from the John Wayne Cancer Institute at Saint John's Health Center, and Judy Dering, PhD, from the David Geffen School of Medicine at UCLA, contributed to the study.

The research was supported with grants from the American Cancer Society (RSG-10-252-01-TBG), Sandy Rollman Ovarian Cancer Foundation and the Pacific Ovarian Cancer Research Consortium (Developmental Grant, P50 CA083636) and the National Center for Advancing Translational Sciences (UL1TR000124).

Citation: Clinical Cancer Research. 2013 Nov 11: Collagen-remodeling gene signature predicts poor survival.