HOW CAN THE TRANSCRIPTOME AND PROTEOME BE USEFUL?
Because each type of molecule reflects the activity of cells and tissues, these molecules are thought to be excellent indicators of health states and prognostic outcomes. Indeed, sequencing of transcriptomes of cancer tissues has revealed novel RNA isoforms that are differentially expressed relative to normal tissues. Importantly, the RNA information can shed light on the various biological pathways that are active, classify the tumor into subtypes, and guide treatment. As a recent example, genomic and transcriptomic analysis has stratified colon cancer into subtypes with differing clinical outcomes. Analysis of the proteome of the same tissues reveals an additional colon cancer subtype. Importantly, only about one-third of potential cancer- driving mutations are expressed as RNA; the expressed protein products or associated pathways are logical targets for drugs.
Another example in which the transcriptome has been shown to be clinically useful is prostate cancer. Many cases of prostate cancer are identified early and not associated with any symptoms, are slow-growing, and, depending on a man’s lifespan, may not ever cause health problems. It is often difficult, however, to distinguish slow-growing forms of prostate cancer from aggressive forms, so by Stage II many men with prostate cancer have their prostates surgically removed and/or receive radiation therapy. These interventions can have side effects, however, such as impotence or urinary incontinence. Recently, tests have become available that assess the expression of a panel of marker genes in a biopsy sample and can distinguish slow-growing from aggressive forms of prostate cancer, thus helping distinguish between patients who need invasive treatments and those who can have their disease managed simply by regular monitoring or “active surveillance.” These gene expression tests are currently performed on a small fraction of the men diagnosed with prostate cancer each year, but this is expected to increase as major medical organizations have begun to incorporate these tests into their prostate management guidelines and large insurers have begun covering them. Similar gene expression assays have a well-established role in managing early breast cancer.