Systematic identification of key genes and pathways in the development of invasive cervical cancer

Gene. 2017 Jun 30:618:28-41. doi: 10.1016/j.gene.2017.03.018. Epub 2017 Mar 21.

Abstract

Background: Cervical cancer progresses through different stages: a long stage of precancerous lesions, then high-grade squamous intraepithelial lesion (HSIL) stage in which precancerous lesions transform into invasive cervical carcinoma, and finally invasive squamous cell carcinomas (SCC) which is difficult to be treated and can be deadly.

Methods and results: To identify critical genes for the development and progression of cervical cancer development, we analyzed an online database comprised of normal squamous cervical epithelia samples, HSIL samples and SCC of cervix. Dysregulated genes were identified in both early stage (from normal to HSIL stage) and late stage (from HSIL stage to SCC stage) of cervical cancer. By overlapping these dysregulated genes, we found that three genes, including CDKN2A, IL1R2 and RFC4, were not only changed in HSIL, but also significantly changed in SCC, indicating that their dysregulation may contribute to cervical cancer development. Several altered pathways during tumor progression were also discovered, including those involved in cell proliferation, cell cycle and cell division.

Conclusions: Our findings suggest that dysregulations of CDKN2A, IL1R2 and RFC4 may contribute to cervical cancer progression and they might be potential diagnostic markers and therapeutic drug targets.

Keywords: Bioinformatics; CDKN2A; Cervical cancer; IL1R2; RFC4.

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p18 / genetics
  • Cyclin-Dependent Kinase Inhibitor p18 / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasm Invasiveness
  • Receptors, Interleukin-1 Type II / genetics
  • Receptors, Interleukin-1 Type II / metabolism
  • Replication Protein C / genetics
  • Replication Protein C / metabolism
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p18
  • IL1R2 protein, human
  • RFC4 protein, human
  • Receptors, Interleukin-1 Type II
  • Replication Protein C