High expression of Kruppel-like factor 4 as a predictor of poor prognosis for cervical cancer patient response to radiotherapy

Tumour Biol. 2017 Jun;39(6):1010428317710225. doi: 10.1177/1010428317710225.

Abstract

Purpose: The aim of this study was to explore the associations of Kruppel-like factor 4 expression with sensitivity to radiation therapy in locally advanced cervical squamous cell carcinoma patients.

Methods: The records of 117 locally advanced cervical squamous cell carcinoma patients were retrospectively reviewed, and Kruppel-like factor 4 expression in cervical carcinoma tissues was examined by immunohistochemical staining. The associations of Kruppel-like factor 4 expression with clinicopathological parameters were analyzed. Survival time was analyzed using Kaplan-Meier analysis and a Cox regression model.

Results: Patients being resistant to radiation therapy were associated with advanced International Federation of Gynecology and Obstetrics stage, tumor diameter (>4 cm), and poor differentiation grade. The high Kruppel-like factor 4 expression level was significantly related to resistance to radiation therapy, including radiation therapy non-response, local recurrence, and distant metastasis. The high Kruppel-like factor 4 expression level was also significantly related to the advanced International Federation of Gynecology and Obstetrics stage and poor differentiation grade. Kaplan-Meier analysis indicates that locally advanced cervical squamous cell carcinoma patients with high Kruppel-like factor 4 expression showed worse progression-free survival and overall survival. Univariate and multivariate Cox regression model analyses suggest that the high Kruppel-like factor 4 expression was one of the high-risk factors associated with poor prognosis in locally advanced cervical squamous cell carcinoma patients after radiation therapy.

Conclusion: Our results suggest that the high Kruppel-like factor 4 expression can be used as a novel biomarker to predict radiation therapy resistance and poor prognosis for locally advanced cervical squamous cell carcinoma.

Keywords: Kruppel-like factor 4; Radiation therapy sensitivity; cervical cancer; immunohistochemistry.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / biosynthesis*
  • Biomarkers, Tumor / genetics
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / radiotherapy
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors / biosynthesis*
  • Kruppel-Like Transcription Factors / genetics
  • Lymphatic Metastasis
  • Middle Aged
  • Prognosis
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / radiotherapy

Substances

  • Biomarkers, Tumor
  • KLF4 protein, human
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors