Identification of early stage recurrence endometrial cancer biomarkers using bioinformatics tools

Oncol Rep. 2020 Sep;44(3):873-886. doi: 10.3892/or.2020.7648. Epub 2020 Jun 16.

Abstract

Endometrial cancer (EC) is the sixth most common cancer in women worldwide. Early diagnosis is critical in recurrent EC management. The present study aimed to identify biomarkers of EC early recurrence using a workflow that combined text and data mining databases (DisGeNET, Gene Expression Omnibus), a prioritization algorithm to select a set of putative candidates (ToppGene), protein‑protein interaction network analyses (Search Tool for the Retrieval of Interacting Genes, cytoHubba), association analysis of selected genes with clinicopathological parameters, and survival analysis (Kaplan‑Meier and Cox proportional hazard ratio analyses) using a The Cancer Genome Atlas cohort. A total of 10 genes were identified, among which the targeting protein for Xklp2 (TPX2) was the most promising independent prognostic biomarker in stage I EC. TPX2 expression (mRNA and protein) was higher (P<0.0001 and P<0.001, respectively) in ETS variant transcription factor 5‑overexpressing Hec1a and Ishikawa cells, a previously reported cell model of aggressive stage I EC. In EC biopsies, TPX2 mRNA expression levels were higher (P<0.05) in high grade tumors (grade 3) compared with grade 1‑2 tumors (P<0.05), in tumors with deep myometrial invasion (>50% compared with <50%; P<0.01), and in intermediate‑high recurrence risk tumors compared with low‑risk tumors (P<0.05). Further validation studies in larger and independent EC cohorts will contribute to confirm the prognostic value of TPX2.

Keywords: endometrial cancer; bioinformatics; biomarkers; recurrence; TPX2.

Publication types

  • Observational Study
  • Validation Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Biopsy
  • Case-Control Studies
  • Cell Cycle Proteins / genetics*
  • Cell Line, Tumor
  • Chemotherapy, Adjuvant
  • Computational Biology
  • Datasets as Topic
  • Disease-Free Survival
  • Endometrial Neoplasms / diagnosis
  • Endometrial Neoplasms / mortality*
  • Endometrial Neoplasms / pathology
  • Endometrial Neoplasms / therapy
  • Endometrium / pathology*
  • Endometrium / surgery
  • Female
  • Gene Expression Profiling
  • Gene Regulatory Networks
  • Humans
  • Kaplan-Meier Estimate
  • Microtubule-Associated Proteins / genetics*
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Recurrence, Local / diagnosis
  • Neoplasm Recurrence, Local / epidemiology*
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Staging
  • Oligonucleotide Array Sequence Analysis
  • Pilot Projects
  • Prognosis
  • Protein Interaction Mapping
  • Protein Interaction Maps / genetics
  • Protein Processing, Post-Translational
  • ROC Curve
  • Risk Assessment / methods

Substances

  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • Microtubule-Associated Proteins
  • TPX2 protein, human