Radiation Response of Cervical Cancer Stem Cells Is Associated with Pretreatment Proportion of These Cells and Physical Status of HPV DNA

Int J Mol Sci. 2021 Feb 1;22(3):1445. doi: 10.3390/ijms22031445.

Abstract

Radio- and chemoresistance of cancer stem cells (CSCs) is considered as one of the possible causes of adverse results of chemoradiotherapy for various malignancies, including cervical cancer. However, little is known about quantitative changes in the CSC subpopulation in the course of treatment and mechanisms for individual response of CSCs to therapy. The purpose of the study was to evaluate the association of radiation response of cervical CSCs with clinical and morphological parameters of disease and features of human papillomavirus (HPV) infection. The proportion of CD44+CD24low CSCs was determined by flow cytometry in cervical scrapings from 55 patients with squamous cell carcinoma of uterine cervix before treatment and after fractionated irradiation at a total dose of 10 Gy. Real-time PCR assay was used to evaluate molecular parameters of HPV DNA. Post-radiation increase in the CSC proportion was found in 47.3% of patients. Clinical and morphological parameters (stage, status of lymph node involvement, and histological type) were not significantly correlated with radiation changes in the CSC proportion. Single- and multifactor analyses revealed two independent indicators affecting the radiation response of CSCs: initial proportion of CSCs and physical status of HPV DNA (R = 0.86, p = 0.001 for the multiple regression model in the whole).

Keywords: cancer stem cells; cervical cancer; flow cytometry; human papillomavirus; radiotherapy.

MeSH terms

  • Adult
  • Aged
  • Alphapapillomavirus*
  • CD24 Antigen / metabolism
  • Carcinoma, Squamous Cell / complications
  • Carcinoma, Squamous Cell / radiotherapy
  • Carcinoma, Squamous Cell / virology
  • DNA, Viral / metabolism
  • Drug Resistance, Neoplasm
  • Female
  • Flow Cytometry
  • Humans
  • Hyaluronan Receptors / metabolism
  • Middle Aged
  • Neoplastic Stem Cells
  • Papillomavirus Infections / complications*
  • Papillomavirus Infections / radiotherapy*
  • Prognosis
  • Real-Time Polymerase Chain Reaction
  • Regression Analysis
  • Uterine Cervical Neoplasms / complications*
  • Uterine Cervical Neoplasms / radiotherapy*
  • Uterine Cervical Neoplasms / virology
  • Young Adult

Substances

  • CD24 Antigen
  • CD24 protein, human
  • CD44 protein, human
  • DNA, Viral
  • Hyaluronan Receptors