Pathway-Structured Predictive Model for Cancer Survival Prediction: A Two-Stage Approach.

Journal Article (Journal Article)

Heterogeneity in terms of tumor characteristics, prognosis, and survival among cancer patients has been a persistent problem for many decades. Currently, prognosis and outcome predictions are made based on clinical factors and/or by incorporating molecular profiling data. However, inaccurate prognosis and prediction may result by using only clinical or molecular information directly. One of the main shortcomings of past studies is the failure to incorporate prior biological information into the predictive model, given strong evidence of the pathway-based genetic nature of cancer, i.e., the potential for oncogenes to be grouped into pathways based on biological functions such as cell survival, proliferation, and metastatic dissemination. To address this problem, we propose a two-stage approach to incorporate pathway information into the prognostic modeling using large-scale gene expression data. In the first stage, we fit all predictors within each pathway using the penalized Cox model and Bayesian hierarchical Cox model. In the second stage, we combine the cross-validated prognostic scores of all pathways obtained in the first stage as new predictors to build an integrated prognostic model for prediction. We apply the proposed method to analyze two independent breast and ovarian cancer datasets from The Cancer Genome Atlas (TCGA), predicting overall survival using large-scale gene expression profiling data. The results from both datasets show that the proposed approach not only improves survival prediction compared with the alternative analyses that ignore the pathway information, but also identifies significant biological pathways.

Full Text

Duke Authors

Cited Authors

  • Zhang, X; Li, Y; Akinyemiju, T; Ojesina, AI; Buckhaults, P; Liu, N; Xu, B; Yi, N

Published Date

  • January 2017

Published In

Volume / Issue

  • 205 / 1

Start / End Page

  • 89 - 100

PubMed ID

  • 28049703

Pubmed Central ID

  • PMC5223526

Electronic International Standard Serial Number (EISSN)

  • 1943-2631

Digital Object Identifier (DOI)

  • 10.1534/genetics.116.189191


  • eng

Conference Location

  • United States