Expression profiling to predict the clinical behaviour of ovarian cancer fails independent evaluation

In the current study we evaluate whether tumour characteristics in an independent set of 49 patients can be predicted using the pilot data set with principal component analysis or LS-SVMs.The results of the principal component analysis suggest that the gene expression data from stage I, platin-sensitive advanced stage and platin-resistant advanced stage tumours in the independent data set did not correspond to their respective classes in the pilot study. Additionally, LS-SVM models built using the data from the pilot study – although they only misclassified one of four stage I tumours and correctly classified all 45 advanced stage tumours – were not able to predict resistance to platin-based chemotherapy. Furthermore, models based on the pilot data and on previously published gene sets related to ovarian cancer outcomes, did not perform significantly better than our models.We discuss possible reasons for failure of the model for predicting response to platin-based chemotherapy and conclude that existing results based on gene expression patterns of ovarian tumours need to be thoroughly scrutinized before these results can be accepted to reflect the true performance of microarray technology.Ovarian cancer ranks fifth when considering cancer mortality in women [1]. Unfortunately clinical or pathologic variables that can reliably predict recurrence in FIGO (Fédération Internationale de Gynécologie Obstétrique) stage I patients or resistance to platin-based chemotherapy in advanced stage disease (FIGO stage III or IV) are not available. The prognosis might be more optimally predicted based on gene expression analysis, since microarrays can capture tumour properties that might not be reflected in the commonly used clinical or histopathological variables at diagnosis.Previously, we performed a pilot study consisting of microarray analysis on three groups of patients: seven stage I without recurrence, seven platin-sensitive advanced stage and six platin-resistant advanced s