Intracellular signaling entropy can be a biomarker for predicting the development of cervical intraepithelial neoplasia

PLoS One. 2017 Apr 28;12(4):e0176353. doi: 10.1371/journal.pone.0176353. eCollection 2017.

Abstract

While the mortality rates for cervical cancer have been drastically reduced after the introduction of the Pap smear test, it still is one of the leading causes of death in women worldwide. Additionally, studies that appropriately evaluate the risk of developing cervical lesions are needed. Therefore, we investigated whether intracellular signaling entropy, which is measured with microarray data, could be useful for predicting the risks of developing cervical lesions. We used three datasets, GSE63514 (histology), GSE27678 (cytology) and GSE75132 (cytology, a prospective study). From the data in GSE63514, the entropy rate was significantly increased with disease progression (normal < cervical intraepithelial neoplasia, CIN < cancer) (Kruskal-Wallis test, p < 0.0001). From the data in GSE27678, similar results (normal < low-grade squamous intraepithelial lesions, LSILs < high-grade squamous intraepithelial lesions, HSILs ≤ cancer) were obtained (Kruskal-Wallis test, p < 0.001). From the data in GSE75132, the entropy rate tended to be higher in the HPV-persistent groups than the HPV-negative group. The group that was destined to progress to CIN 3 or higher had a tendency to have a higher entropy rate than the HPV16-positive without progression group. In conclusion, signaling entropy was suggested to be different for different lesion statuses and could be a useful biomarker for predicting the development of cervical intraepithelial neoplasia.

MeSH terms

  • Computational Biology / methods*
  • Disease Progression
  • Entropy*
  • Female
  • Human papillomavirus 16 / physiology
  • Humans
  • Intracellular Space / metabolism*
  • Prognosis
  • Signal Transduction*
  • Uterine Cervical Dysplasia / diagnosis*
  • Uterine Cervical Dysplasia / pathology*
  • Uterine Cervical Dysplasia / virology

Grants and funding

Support was provided by the Practical Research for Innovative Cancer Control from Japan Agency for Medical Research and Development, AMED No. 15ck0106178h0001(KK) [http://www.amed.go.jp]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.