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TECH TIPS OMICS not reliable. "Our idea was to use gene expression analysis to better predict the prognosis of stage II and III colon cancer patients," ex- plains Dr. Zhang. A challenging aspect is that different gene expression signatures from different stud- ies often do not overlap with each other. "We tried to find common biological themes across previously published signatures, and by integrating them into biological networks, we generated a gene expression signature that is more biologically meaningful and, ad- ditionally, has a good prognostic value," says Dr. Zhang. This approach revealed that genes with mechanistically important roles in colorectal cancer may be used to develop reliable prog- nostic models that accurately predict recur- rences and the response to adjuvant chemo- therapy. Gene expression-based stratification of these two cancer stages is crucial for in- creasing survival and the quality of life, while minimizing the chemotherapy-associated toxic effects and the financial costs involved. 3D Systems While historically the biology of specific cell types was examined by using homogenous monolayer cultures grown in vitro, this experi- mental approach tends to be an oversimplifi- cation. As opposed to the culture systems that often use a single cell type, organs consist of a complex network of multiple cell types that also includes extracellular matrix, growth and signaling factors, and other components. Dynamic bidirectional signaling events within this microenvironment assume key functions in tissue maintenance and in sup- pressing or promoting tumor development. The microenvironment is one of the most important factors that emerged in recent years to shape cellular behavior, and three- dimensional (3D) cell culture systems, which more faithfully reflect the in vivo conditions, have increasingly found applications in many biomedical areas. Nils Cordes, M.D., Ph.D., professor of molecular and cellular radiobiology at the Dresden University of Technology, and col- leagues have comparatively examined the gene expression profiles in two exponentially growing human cancer cell lines—lung carci- noma and squamous cell carcinoma—grown in a 3D extracellular matrix scaffold or as a conventional two-dimensional monolayer. "The idea behind this experiment was that in vitro cell cultures that we are work- ing with do not always reflect the in vivo situations, and we wanted to know whether the differential gene expression shapes tumor cell sensitivity to radiation and chemothera- peutics," explains Dr. Cordes. The technique revealed significant gene expression changes between the two condi- tions. "We showed that there was a differential gene expression pattern, between the 3D and the 2D conditions, in genes encoding ECM proteins, integrins, cell shape proteins, and proteins linked to morphology, but not to DNA repair," notes Dr. Cordes. Moreover, under the 3D growth condi- tions, cells showed an increased resistance to radiotherapy and chemotherapy as compared to the 2D conditions, pointing toward the importance of the growth conditions in shap- ing gene expression. Important in this context is another study from Dr. Cordes' group, in which differences in cell cycling, oxygen lev- els, and radiation dosimetry were ruled out as critical determinants of higher tumor cell survival levels under 3D growth conditions. Few advances have reshaped biomedical and clinical areas within such a short time, and to such a great extent, as the ones that marked gene expression analysis. Technolog- ical developments, their intimate integration with many basic science disciplines, and a growing number of clinical applications have been defining this field for the past decade. While collecting increasingly sophisti- cated and complex datasets has undoubtedly played an instrumental role, perhaps an even greater impact was exerted by the develop- ment and implementation of novel concep- tual frameworks, a theme that provides a central learning point and was so relevantly expressed in Sir William Bragg's words: "The important thing in science is not so much to obtain new facts as to discover new ways of thinking about them." 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