Co-expression of CD147 and GLUT-1 indicates radiation resistance and poor prognosis in cervical squamous cell carcinoma

Abstract

The aim of this study was to investigate the association of CD147 and GLUT-1, which play important roles in glycolysis in response to radiotherapy and clinical outcomes in patients with locally advanced cervical squamous cell carcinoma (LACSCC). The records of 132 female patients who received primary radiation therapy to treat LACSCC at FIGO stages IB-IVA were retrospectively reviewed. Forty-seven patients with PFS (progression-free survival) of less than 36 months were regarded as radiation-resistant. Eighty-five patients with PFS longer than 36 months were regarded as radiation-sensitive. Using pretreatment paraffin-embedded tissues, we evaluated CD147 and GLUT-1 expression by immunohistochemistry. Overexpression of CD147, GLUT-1, and CD147 and GLUT-1 combined were 44.7%, 52.9% and 36.5%, respectively, in the radiation-sensitive group, and 91.5%, 89.4% and 83.0%, respectively, in the radiation-resistant group. The 5-year progress free survival (PFS) rates in the CD147-low, CD147-high, GLUT-1-low, GLUT-1-high, CD147- and/or GLUT-1-low and CD147- and GLUT-1- dual high expression groups were 66.79%, 87.10%, 52.78%, 85.82%, 55.94%, 82.90% and 50.82%, respectively. CD147 and GLUT-1 co-expression, FIGO stage and tumor diameter were independent poor prognostic factors for patients with LACSCC in multivariate Cox regression analysis. Patients with high expression of CD147 alone, GLUT-1 alone or co-expression of CD147 and GLUT-1 showed greater resistance to radiotherapy and a shorter PFS than those with low expression. In particular, co-expression of CD147 and GLUT-1 can be considered as a negative independent prognostic factor.

Keywords: CD147; GLUT-1; Radiation resistance; cervical carcinoma; glycolysis; immunohistochemistry.

Figure 1

Representative examples of CD147 and GLUT-1 staining of tumor in the radiation-resistant group and radiation-sensitive group. A: Strong positive staining of CD147 in the radiation-resistant group; B: Weak positive staining of CD147 in the radiation-sensitive group; C: Strong positive staining of GLUT-1 in the radiation-resistant group; D: Weak positive staining of GLUT-1 in the radiation-sensitive group. The bar size is the same for all the figures. Original magnification ×400.

Figure 2

Kaplan–Meier survival curves according to CD147 and GLUT1 protein expression status for LACSCC patients. A: The 5-year progression-free survival (PFS) rates were 87.10% and 52.78% in patients with low CD147 expression (n=51) and high CD147 expression (n=81), respectively. There was a significant difference in the overall survival rate between the two groups (p<0.001). B: The 5-year PFS rates were 85.82% and 55.94% in patients with low GLUT-1 expression (n=45) and high GLUT-1 expression (n=87), respectively. There was a significant difference in the overall survival rate between the two groups (p<0.001). C: The 5-year PFS rates were 82.90% and 50.82% in patients that showed CD147 and/or GLUT-1 low expression (n=62) and CD147 and GLUT-1 dual high expression (n=70), respectively. There was a significant difference in the overall survival rate between the two groups (p<0.001). D: The 5-year PFS rate was 66.79% in all of the 132 patients with LACSCC.