In biomedical studies it is of substantial interest to develop risk prediction scores using high-dimensional data such as gene expression data for clinical endpoints that are subject to censoring. In the presence of well-established clinical risk fac
tors, investigators often prefer a procedure that also adjusts for these clinical variables. While accelerated failure time (AFT) models are a useful tool for the analysis of censored outcome data, it assumes that covariate effects on the logarithm of time-to-event are linear, which is often unrealistic in practice. We propose to build risk prediction scores through regularized rank estimation in partly linear AFT models, where high-dimensional data such as gene expression data are modeled linearly and important clinical variables are modeled nonlinearly using penalized regression splines. We show through simulation studies that our model has better operating characteristics compared to several existing models. In particular, we show that there is a nonnegligible effect on prediction as well as feature selection when nonlinear clinical effects are misspecified as linear. This work is motivated by a recent prostate cancer study, where investigators collected gene expression data along with established prognostic clinical variables and the primary endpoint is time to prostate cancer recurrence.
Lung cancer is among the most common cancers in the United States, in terms of incidence and mortality. In 2009, it is estimated that more than 150,000 deaths will result from lung cancer alone. Genetic information is an extremely valuable data sourc
e in characterizing the personal nature of cancer. Over the past several years, investigators have conducted numerous association studies where intensive genetic data is collected on relatively few patients compared to the numbers of gene predictors, with one scientific goal being to identify genetic features associated with cancer recurrence or survival. In this note, we propose high-dimensional survival analysis through a new application of boosting, a powerful tool in machine learning. Our approach is based on an accelerated lifetime model and minimizing the sum of pairwise differences in residuals. We apply our method to a recent microarray study of lung adenocarcinoma and find that our ensemble is composed of 19 genes, while a proportional hazards (PH) ensemble is composed of nine genes, a proper subset of the 19-gene panel. In one of our simulation scenarios, we demonstrate that PH boosting in a misspecified model tends to underfit and ignore moderately-sized covariate effects, on average. Diagnostic analyses suggest that the PH assumption is not satisfied in the microarray data and may explain, in part, the discrepancy in the sets of active coefficients. Our simulation studies and comparative data analyses demonstrate how statistical learning by PH models alone is insufficient.
