Prognostic markers in lung cancer: is it ready for prime time?

Non-small cell lung cancer (NSCLC) is a heterogeneity disease and to date, specific clinical factors and tumor stage are established as prognostic markers. Nevertheless, prognosis within stage may vary significantly. During the last 3 decades, genes/proteins that drive tumor initiation and progression, such as oncogenes and tumor suppressor genes have been studied as additional potential prognostic markers. The protein markers as evaluated by immunohistochemistry (IHC) have previously dominated these studies. However, with the development of high-throughput techniques to interrogate genome wide genetic or gene expression changes, DNA (copy number and mutation) and RNA (mRNA and microRNA) based markers have more recently been studied as prognostic markers. Largely due to the heterogeneity and complexity of NSCLC, single gene markers including KRAS mutation has not been validated as strong prognostic markers. In contrast, several gene expression signatures representing mRNA levels of multiple genes have been developed and validated in multiple microarray datasets of independent patient cohorts. The salient features of these gene signatures and their potential value to predict benefit from adjuvant chemotherapy is discussed.