TRANSCRIPTOMIC AND GERMLINE GENOMIC APPROACHES FOR THE DISCOVERY OF PROGNOSTIC AND PREDICTIVE CANCER BIOMARKERS
Prediction of prognosis and therapeutic outcome in cancer patients is mostly based on conventional clinical and pathological parameters. However, cancers are biologically heterogeneous diseases and this confers considerable variability in the clinical course independently of stage and other conventional parameters.
Genomic and transcriptomic biomarkers may be responsible for cancer initiation and progression and lead to variable prognosis and therapeutic outcome. These molecular biomarkers could thus be useful to identify high risk patients and patients responsive/resistant to pharmacological therapies.
The role of germline genetic variation on cancer prognosis and on treatment response is a promising field of research. Studies have produced some interesting results on the impact of germline genetic variation in candidate genes involved in pathways related to metabolism, immune function, and DNA repair on patient and treatment outcomes. However, most studies to date have been conducted with the candidate gene approach and have been limited by small sample sizes. The genome-wide approach has been much more successful in identifying genetic variants linked to cancer risk but only a few comprehensive genome-wide association studies have been conducted to identify genetic markers for cancer prognosis.
We will report the results of studies aimed at identifying gene expression profiles predictive of prognosis in early-stage colorectal cancer patients candidate to chemotherapy and germline genetic variations associated with prognosis in patients with diffuse large B cell lymphoma treated with immunochemotherapy. The results of these studies have identified potential prognostic and predictive molecular markers and generated important hypotheses which, if supported by further analyses, could be prospectively tested in the clinic.
Department of Health Sciences
University of Florence