Gene Signature May Predict Bladder Cancer Progression

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It may soon be possible to identify which bladder cancer patients are responding to treatment and which may have disease progression. Investigators at Dartmouth's Norris Cotton Cancer Center in Lebanon, New Hampshire have discovered that the previously identified E2F4 signature in breast cancer can be utilized to predict prognosis and response to therapy in bladder cancer.¹

The researchers conducted an integrative analysis that included gene expression profiles for more than 800 bladder tumor samples with clinical information. They found that the E2F4 signature is predictive of the progression of both nonmuscle-invasive and muscle-invasive bladder cancer.  "It can also predict the responsiveness of patients to intravesical Bacillus Calmette-Guerin (BCG) immunotherapy. Our results suggest that patients with positive E2F4 scores benefit significantly from BCG therapy, while the progression of patients with negative E2F4 scores does not show significant difference from untreated patients,” said lead study investigator Chao Cheng, PhD, who is an Assistant Professor of Genetics at Dartmouth's Geisel School of Medicine.

Intravesical BCG therapy has been widely used to treat patients with nonmuscle-invasive bladder cancer for many years. It has an estimated 60% success rate in preventing recurrence or progression. Until now, there has been no effective biomarker to identify which patients are responsive to this therapy. 

Dr. Cheng and colleagues collected information from the public database Gene Expression Omnibus (GEO) and the molecular signature was investigated in a single bladder cancer dataset. In addition, the researchers confirmed its effectiveness in two meta-bladder datasets consisting of specimens from multiple independent studies. The investigators found that the results were consistent in different datasets and demonstrated that the E2F4 score is predictive of clinical outcomes in bladder cancer. The researchers found that those patients whose tumors exhibited an E2F4 score >0 had significantly shorter survival times than those with an E2F4 score <0.  This held true for both nonmuscle-invasive and muscle-invasive bladder cancer.

"An integration of genomic data with clinical information will provide new biological insight in cancer biology and identify new biomarkers for aiding clinical practice," explained Cheng. "Such translational studies need collective efforts from cancer biologists, clinicians, and computational biologists."

Cheng and his team, who published their findings in Molecular Cancer Research, plan more detailed research to validate the prognostic value of the E2F4 signature in predicting bladder cancer progression or recurrence in an independent dataset.² The researchers hope these studies will lead to a convenient and practical clinical test based on E2F4 to predict the efficacy of the BCG immunotherapy for bladder cancer patients.

References:

• Dartmouth-Hitchcock Norris Cotton Cancer Center. (2015). Breast Cancer Gene Signature Predicts Bladder Cancer Progression.
• Cheng C, Varn FS, Marsit CJ. (2015). E2F4 Program is Predictive of Progression and Intravesical Immunotherapy Efficacy in Bladder Cancer. Molecular Cancer Research.