To evaluate the potential of gene expression signatures to predict response to treatment in locally advanced cervical cancer treated with definitive chemotherapy and radiation.
Materials/Methods
Biopsies were collected before treatment and before the first implant (mid-treatment biopsy) from patients participating on a phase II RTOG trial evaluating the benefit of celecoxib in addition to cisplatin chemotherapy and radiation therapy for locally advanced cervical cancer. Gene expression profiling was performed on all samples of adequate quality, and signatures of pre, mid-treatment, and changing gene expression patterns between pre and mid-treatment samples were evaluated. The ability of the gene signatures to predict local control versus local failure was evaluated. Two group t tests were performed to identify the initial gene set. Supervised classification methods were used to enrich the gene sets. The results were further validated by leave one out or 2-fold cross-validation.
Results
22 patients had suitable material from pretreatment samples for analysis and there were 13 paired samples (pre-treatment mid-treatment). Initial and mid-treatment gene expression signatures alone were unable to separate patients by local control status. However, the altered gene expression signatures between the initial and mid-treatment biopsies were able to predict response to treatment, separating patients with local failures from those who achieved local control. Importantly, the gene signature pattern achieving separation between local failure and local control contained only 7 genes. The in-sample prediction rate, leave one out prediction rate, and two-fold prediction rate are 100% for this seven gene set. This signature was enriched for cell cycle genes.
Conclusions
Although the numbers in the study were small, changes in gene expression during therapy in cervical cancer can predict outcome as measured by local control in cervical cancer. These data support the notion that alteration of cell cycle parameters may be pivotal in successful chemoradiation protocols. These are important first steps towards tailoring therapy to individuals. Further translation research trials are warranted evaluating gene expression profiling in cervix and other cancers. These data indicate that attention to changes in gene expression patterns is important.
Supported by RTOG U10 CA21661, CCOP U10 CA37422, and Stat U10 CA32115 grants from the NCI. This abstract's contents are the sole responsibility of the authors and do not necessarily represent the official views of the NCI.
1Yale University School of Medicine, New Haven, CT
Author Disclosure: J.B. Weidhaas, None; S. Li, None; K. Winter, None; J. Ryu, None; A. Jhingra, None; B. Miller, None; A. Dicker, None; D. Gaffney, None.
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