Weibull regression with Bayesian variable selection to identify prognostic tumour markers of breast cancer survival

Stat Methods Med Res. 2017 Feb;26(1):414-436. doi: 10.1177/0962280214548748. Epub 2016 Sep 30.

Abstract

As data-rich medical datasets are becoming routinely collected, there is a growing demand for regression methodology that facilitates variable selection over a large number of predictors. Bayesian variable selection algorithms offer an attractive solution, whereby a sparsity inducing prior allows inclusion of sets of predictors simultaneously, leading to adjusted effect estimates and inference of which covariates are most important. We present a new implementation of Bayesian variable selection, based on a Reversible Jump MCMC algorithm, for survival analysis under the Weibull regression model. A realistic simulation study is presented comparing against an alternative LASSO-based variable selection strategy in datasets of up to 20,000 covariates. Across half the scenarios, our new method achieved identical sensitivity and specificity to the LASSO strategy, and a marginal improvement otherwise. Runtimes were comparable for both approaches, taking approximately a day for 20,000 covariates. Subsequently, we present a real data application in which 119 protein-based markers are explored for association with breast cancer survival in a case cohort of 2287 patients with oestrogen receptor-positive disease. Evidence was found for three independent prognostic tumour markers of survival, one of which is novel. Our new approach demonstrated the best specificity.

Keywords: Bayesian variable selection; MCMC; breast cancer; gene expression; penalised regression; reversible jump; stability selection; survival analysis.

MeSH terms

  • Algorithms*
  • Bayes Theorem*
  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality*
  • Female
  • Humans
  • Prognosis
  • Receptors, Estrogen / metabolism
  • Regression Analysis*
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • Receptors, Estrogen