Alternative Polyadenylation Patterns for Novel Gene Discovery and Classification in Cancer

Neoplasia. 2017 Jul;19(7):574-582. doi: 10.1016/j.neo.2017.04.008. Epub 2017 Jun 15.

Abstract

Certain aspects of diagnosis, prognosis, and treatment of cancer patients are still important challenges to be addressed. Therefore, we propose a pipeline to uncover patterns of alternative polyadenylation (APA), a hidden complexity in cancer transcriptomes, to further accelerate efforts to discover novel cancer genes and pathways. Here, we analyzed expression data for 1045 cancer patients and found a significant shift in usage of poly(A) signals in common tumor types (breast, colon, lung, prostate, gastric, and ovarian) compared to normal tissues. Using machine-learning techniques, we further defined specific subsets of APA events to efficiently classify cancer types. Furthermore, APA patterns were associated with altered protein levels in patients, revealed by antibody-based profiling data, suggesting functional significance. Overall, our study offers a computational approach for use of APA in novel gene discovery and classification in common tumor types, with important implications in basic research, biomarker discovery, and precision medicine approaches.

MeSH terms

  • 3' Untranslated Regions
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks
  • Genetic Association Studies*
  • Humans
  • Neoplasms / diagnosis*
  • Neoplasms / genetics*
  • Polyadenylation*
  • RNA, Messenger*
  • Transcriptome
  • Workflow

Substances

  • 3' Untranslated Regions
  • RNA, Messenger