Putative biomarkers for cervical cancer: SNVs, methylation and expression profiles

Mutat Res Rev Mutat Res. 2017 Jul:773:161-173. doi: 10.1016/j.mrrev.2017.06.002. Epub 2017 Jun 30.

Abstract

Cervical cancer is primarily caused by Human papillomavirus (HPV) infection, but other factors such as smoking habits, co-infections and genetic background, can also contribute to its development. Although this cancer is avoidable, it is the fourth most frequent type of cancer in females worldwide and can only be treated with chemotherapy and radical surgery. There is a need for biomarkers that will enable early diagnosis and targeted therapy for this type of cancer. Therefore, a systems biology pipeline was applied in order to identify potential biomarkers for cervical cancer, which show significant reports in three molecular aspects: DNA sequence variants, DNA methylation pattern and alterations in mRNA/protein expression levels. CDH1, CDKN2A, RB1 and TP53 genes were selected as putative biomarkers, being involved in metastasis, cell cycle regulation and tumour suppression. Other ten genes (CDH13, FHIT, PTEN, MLH1, TP73, CDKN1A, CACNA2D2, TERT, WIF1, APC) seemed to play a role in cervical cancer, but the lack of studies prevented their inclusion as possible biomarkers. Our results highlight the importance of these genes. However, further studies should be performed to elucidate the impact of DNA sequence variants and/or epigenetic deregulation and altered expression of these genes in cervical carcinogenesis and their potential as biomarkers for cervical cancer diagnosis and prognosis.

Keywords: Clinical markers; Genetic panel; Prognostic factors; Therapeutics.

Publication types

  • Review

MeSH terms

  • Antigens, CD
  • Biomarkers, Tumor / genetics*
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p18 / genetics
  • Cyclin-Dependent Kinase Inhibitor p18 / metabolism
  • DNA Methylation*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Retinoblastoma Binding Proteins / genetics
  • Retinoblastoma Binding Proteins / metabolism
  • Sequence Analysis, DNA
  • Transcriptome*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism
  • Uterine Cervical Neoplasms / diagnosis*
  • Uterine Cervical Neoplasms / genetics*

Substances

  • Antigens, CD
  • Biomarkers, Tumor
  • CDH1 protein, human
  • CDKN2A protein, human
  • Cadherins
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p18
  • RB1 protein, human
  • RNA, Messenger
  • Retinoblastoma Binding Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Ubiquitin-Protein Ligases