Elevated expression of the centromere protein-A(CENP-A)-encoding gene as a prognostic and predictive biomarker in human cancers

Int J Cancer. 2016 Aug 15;139(4):899-907. doi: 10.1002/ijc.30133. Epub 2016 Apr 21.

Abstract

Centromere protein-A (CENP-A), a histone-H3 variant, plays an essential role in cell division by ensuring proper formation and function of centromeres and kinetochores. Elevated CENP-A expression has been associated with cancer development. This study aimed to establish whether elevated CENP-A expression can be used as a prognostic and predictive cancer biomarker. Molecular profiling of CENP-A in human cancers was investigated using genomic, transcriptomic and patient information from databases, including COSMIC, Oncomine, Kaplan-Meier plotter and cBioPortal. A network of CENP-A co-expressed genes was derived from cBioPortal and analyzed using Ingenuity Pathway Analysis (IPA) and Oncomine protocols to explore the function of CENP-A and its predictive potential. Transcriptional and post-transcriptional regulation of CENP-A expression was analyzed in silico. It was found that CENP-A expression was elevated in 20 types of solid cancer compared with normal counterparts. Elevated CENP-A expression highly correlated with cancer progression and poor patient outcome. Genomic analysis indicated that the elevated CENP-A expression was not due to alterations in the sequence or copy number of the CENP-A gene. Furthermore, CENP-A can be regulated by key oncogenic proteins and tumor-suppressive microRNAs. CENP-A co-expression network analysis indicated that CENP-A function is associated with cell cycle progression. Oncomine analysis showed a strong correlation between elevated CENP-A expression and oncolytic response of breast cancer patients to taxane-based chemotherapy. In conclusion, elevated CENP-A expression is coupled to malignant progression of numerous types of cancer. It may be useful as a biomarker of poor patient prognosis and as a predictive biomarker for taxane-based chemotherapy.

Keywords: CENP-A; centromere protein-A; co-expression network; predictive biomarker; prognostic biomarker.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantigens / genetics*
  • Biomarkers, Tumor*
  • Centromere Protein A
  • Chromosomal Proteins, Non-Histone / genetics*
  • Databases, Genetic
  • Gene Expression Regulation, Neoplastic
  • Gene Expression*
  • Gene Regulatory Networks
  • Humans
  • Kaplan-Meier Estimate
  • Mutation
  • Neoplasm Metastasis
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Neoplasms / mortality*
  • Prognosis
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / genetics
  • Receptors, Progesterone / metabolism
  • Signal Transduction

Substances

  • Autoantigens
  • Biomarkers, Tumor
  • CENPA protein, human
  • Centromere Protein A
  • Chromosomal Proteins, Non-Histone
  • Receptors, Estrogen
  • Receptors, Progesterone