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Lung Cancer Systems Genetics
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H. Expression Profiling and Diagnostics Development
Another research focus in the Thoracic Oncology Program is on gene expression-the output of gene products within a cancer cell. A common measure of gene expression is the level of messenger RNA (mRNA) being produced. An mRNA is a molecule that carries the blueprint for production of cellular proteins. The amount of mRNA present suggests what genes are active within the cell. The unique pattern of gene activity serves as a "genetic signature" that can be correlated with clinical outcomes and can thereby drive treatment decisions.
An interesting feature of lung cancer is that patients who survive the illness for at least three years without recurrence tend not to succumb to it at all. Although histopathological data are unable to distinguish between the more aggressive form of the cancer and its milder counterpart, we proposed that there is a genotypic distinction between the two forms. Quantitative PCR (qPCR) is a method by which levels of mRNA can be measured relative to a "housekeeping" gene--a gene whose mRNA levels are expressed consistently across tumor and normal cells. We recently completed a large-scale microarray and qPCR study comparing specimens from Stage I adenocarcinoma patients with no neoadjuvant chemotherapy who survived the three year mark without recurrence to similar patients for whom the disease proved lethal to determine whether any genes commonly overexpressed in cancer are specifically implicated in one group of patients versus the other. We found a distinct four gene signature overexpressed in patients with the more aggressive lung cancer. Based upon these results, we hope to develop a clinically relevant assay correlating long-term patient survival with the mRNA expression levels of these four genes of interest. Such an assay might aid in developing a more individualized course of treatment, perhaps avoiding physiologically taxing chemotherapy and radiation treatments for those patients who fit the profile for milder disease. Our group aims to develop similar expression assays to correlate staging and gene expression in other thoracic carcinomas.