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Clinical Cancer Research Vol. 9, 5486-5492, November 15, 2003
© 2003 American Association for Cancer Research


Molecular Oncology, Markers, Clinical Correlates

Expression Genomics of Cervical Cancer

Molecular Classification and Prediction of Radiotherapy Response by DNA Microarray

Yick Fu Wong1,9, Zachariah E. Selvanayagam2,9, Nien Wei5, Joseph Porter6, Ragini Vittal7, Rong Hu8, Yong Lin4, Jason Liao4, Joe Weichung Shih4, Tak Hong Cheung1, Keith Wing Kit Lo1, So Fan Yim1, Shing Kai Yip1, Danny Tse Ngong1, Nelson Siu1, Loucia Kit Ying Chan1, Chun Sing Chan1, Tony Kong8, Elena Kutlina3, Randall D. McKinnon3, David T. Denhardt6, Khew-Voon Chin7 and Tony Kwok Hung Chung1

1 Department of Obstetrics and Gynecology, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, People’s Republic of China; Departments of
2 Pediatrics and
3 Surgery and
4 The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, New Jersey;
5 Northridge Co., Warren, New Jersey; and
6 Department of Cell Biology and Neuroscience,
7 Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, and
8 Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey

ABSTRACT

Purpose: The incidence and mortality rates of cervical cancer are declining in the United States; however, worldwide, cervical cancer is still one of the leading causes of death in women, second only to breast cancer. This disparity is at least partially explained by the absence of or comparatively ineffective screening programs in the developing world. Recent advances in expression genomics have enabled the use of DNA microarray to profile gene expression of various cancers. These expression profiles may be suitable for molecular classification and prediction of disease outcome and treatment response. We envision that expression genomics applied in cervical cancer may provide a more rational approach to the classification and treatment of the disease.

Experimental Design: In this report, we examined the expression profiles of cervical cancer compared with normal cervical tissues in DNA microarrays that contained approximately 11,000 features that correspond to either human transcripts with known function or anonymous expressed sequence tags.

Results: Our results showed that normal cervical tissues were completely segregated from the cancer samples using about 40 genes whose expressions were significantly different between these specimens. In addition, clinical stage IB and stage IIB tumors could also be classified based on their signature expression patterns. Most importantly, some of the tumor samples were further stratified into two major groups based on their response to radiotherapy, and we were able to predict the response of these patients to radiotherapy from their expression profiles.

Conclusions: Gene expression profiling by DNA microarray may be used for further molecular classification of disease stages and prediction of treatment response in cervical cancer.




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