Researchers Report Robust Markers for Stomach Cancer Diagnoses

Researchers at the Institute for Systems Biology (ISB) in Seattle, WA and The University of Texas M.D. Anderson Cancer Center in Houston, TX have discovered a novel and accurate approach for distinguishing two very similar types of stomach cancer. Their study is being published online this week in the Proceedings of the National Academy of Sciences of the USA (www.pnas.org). According to Nathan Price, Ph.D, senior research scientist at ISB and lead author, the results of our research are a prime example of how genomics and systems biology approaches are beginning to impact medicine and to significantly improve the lives of patients.

The two cancers, gastrointestinal stromal tumor (GIST) and leiomyosarcoma (LMS), have very similar appearances under the microscope during routine pathological evaluation, but are dissimilar diseases and are treated differently. GIST patients respond poorly to standard chemotherapy, but approximately 80% benefit from the oral drug Gleevec and experience extended survival. LMS, on the other hand, is resistant to Gleevec, but patients benefit from standard, cytotoxic, sarcoma chemotherapy. Thus, the appropriate diagnosis of these cancers has a critical impact on very different decisions for treatment.

The current diagnostic approach relies on multiple molecular markers and tedious processing. Using genomics and systems biology approaches, the Seattle and Houston researchers have discovered a simple molecular classifier that can differentiate these two cancer types with near perfect accuracy, significantly outperforming the previously best test.

The classifier they have found is based on a simple concept: the expression ratio between two genes. For instance, if one gene, OBSCN, is more abundant than the other, C9orf65, then the cancer is a GIST; otherwise, it is an LMS. Because of the simplicity and accuracy of this test, it has the potential to be quickly implemented into clinical practice, with the ultimate goal of benefiting patients by guiding appropriate treatment for the cancers.

Significantly, study co-authors from M. D. Anderson and the ISB conclude that the genetic analytical technique employed with these two stomach cancers will have wider application in more individualized diagnosis and treatment of other types of closely related cancers.

ISB faculty joining Dr. Price in authoring the article are professor Leroy Hood, M.D., Ph.D., president of the Institute, and associate professor Ilya Shmulevich, Ph.D. Hood, underscoring the importance of the study´s results, states that, simple, accurate and early diagnostic markers are critical to the successful treatment of most cancers. This example provides an early glimpse at the power of selecting diagnostic markers with genomics and systems biology approaches.

Authors from M. D. Anderson include Wei Zhang, Ph.D., Jonathan Trent, M.D., Ph.D., Adel El-Naggar, M.D., Ph.D., David Cogdell, Ellen Taylor, Kelly Hunt, M.D., and Raphael E. Pollock, M.D., Ph.D.

This research was funded by the National Cancer Institute and the National Institute of General Medical Sciences, both of the National Institutes of Health; the Commonwealth Foundation for Cancer Research, the American Cancer Society, the Texas Tobacco Settlement Fund, and by grants from the Michael and Betty Kadoorie Foundation and the Goodwin Fund.

About the Institute for Systems Biology:

The Institute for Systems Biology (ISB) is an internationally renowned, non-profit research institute headquartered in Seattle and dedicated to the study and application of systems biology. Founded by Leroy Hood, Alan Aderem and Ruedi Aebersold, ISB seeks to unravel the mysteries of human biology and identify strategies for predicting and preventing diseases such as cancer, diabetes and AIDS. ISB´s systems approach integrates biology, computation and technological development, enabling scientists to analyze all elements in a biological system rather than one gene or protein at a time. Founded in 2000, the Institute has grown to 12 faculty and more than 200 staff members; an annual budget of more than $25 million; and an extensive network of academic and industrial partners. For more information about ISB, visit www.systemsbiology.org