This study was done to validate the discriminative performance of proposed prognostic gene expression signatures at a level of rigor sufficient to support clinical use.
The two-stage validation used independent core laboratories, objective quality control standards, locked test parameters, and large multi-institutional specimens and data sets. The first stage validation confirmed a signature’s ability to stratify patient survival. Participants were prospectively enrolled in institutional or cooperative group biospecimen and data collection protocols. All cases underwent a central review of clinical, pathologic, and biospecimen parameters using objective criteria to determine final inclusion. Primary selection required that a signature significantly predict 3-year survival after surgical resection in cohort I. Signatures meeting this criterion were further tested in cohort II, comparing risk prediction using baseline risk factors alone versus in combination with the signature.
Male sex, advanced age, and higher stage were associated with shorter survival in cohort I and established a baseline clinical model. Of the three signatures validated in cohort I, one signature was validated in cohort II and statistically significantly enhanced the prognosis relative to the baseline model.
These results of this study represent the first rigorous validation of a test appropriate to direct adjuvant treatment or clinical trials for patients with lung squamous cell carcinoma.