HK2 is a radiation resistant and independent negative prognostic factor for patients with locally advanced cervical squamous cell carcinoma

Int J Clin Exp Pathol. 2015 Apr 1;8(4):4054-63. eCollection 2015.


The mechanism by which overexpression of hexokinase 2 (HK2) indicates locally advanced cervical squamous cell carcinoma (LACSCC) with radio-resistance is still unknown despite being an independent biomarker of poor prognosis. Here, we retrospectively analyzed 132 female patients receiving radiotherapy for cervical squamous cell carcinoma including 85 radiation-sensitive cases and 47 radiation-resistant cases. The expression of HK2 was examined by immunohistochemistry. The percentage of high HK2 expression in the radiation-resistant group differed from the radiation-sensitive group with statistical significance (P < 0.001) even if divided into three subgroups including a lower 5-year progression free survival group (PFS) for comparison (P < 0.001). The Kaplan Meier curve analysis showed that there were differences between the two groups (P < 0.001). Therefore, this study proves a close relationship between HK2 expression and radio-resistance. Multivariate Cox regression analysis implied that HK2 was an independent prognostic indicator of cervical squamous carcinoma (HR (95% CI), 2.940 (1.609, 1.609); P = 0.002).

Keywords: HK2; Locally advanced cervical squamous cell carcinoma; glycolysis; immunohistochemistry; radiation resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Brachytherapy* / adverse effects
  • Brachytherapy* / mortality
  • Carcinoma, Squamous Cell / enzymology*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / radiotherapy*
  • Chi-Square Distribution
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Hexokinase / analysis*
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Middle Aged
  • Multivariate Analysis
  • Proportional Hazards Models
  • Radiation Tolerance*
  • Retrospective Studies
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Up-Regulation
  • Uterine Cervical Neoplasms / enzymology*
  • Uterine Cervical Neoplasms / mortality
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / radiotherapy*


  • Biomarkers, Tumor
  • HK2 protein, human
  • Hexokinase