Association of cyclin D1 and survivin expression with sensitivity to radiotherapy in patients with nasopharyngeal carcinoma

Abstract

ABSTRACT. The association between cyclin D1 and survivin protein expressions with radiotherapy sensitivity in patients with nasopharyngeal carcinoma was investigated. Biopsy specimens of 72 patients with nasopharyngeal carcinoma were collected before the initiation of radiotherapy (49 cases were in the radiationsensitive group and 23 cases were in the radiation-insensitive group). Conventional hematoxylin and eosin staining was used for tissue typing. The immunohistochemical SP method was used to detect cyclin D1 and survivin protein expression levels. The IBM SPSS Statistics 20 statistical software was applied for conducting the chi-squared test and the Spearman correlation analysis. In the 72 cases, the high expression rates of cyclin D1 were 28.6% (14/49) and 69.6% (16/23) in the radiotherapy-sensitive group and in the radiotherapy-insensitive group, respectively, and the differences between groups were statistically significant (P < 0.05). The high expression rates of survivin were 34.7% (17/49) and 73.9% (17/23) in the radiotherapy-sensitive group and in the radiotherapy-insensitive group, respectively, which differed significantly (P < 0.05). The protein expressions of cyclin D1 and survivin were positively correlated (Spearman's r = 0.353, P < 0.05). Cyclin D1 and survivin expression levels were negatively correlated with the radiosensitivity of nasopharyngeal carcinoma. Cyclin D1 and survivin may be used as molecular markers to predict the sensitivity of radiotherapy.

The role of cyclin D1 and vascular endothelial growth factor (VEGF) in radiotherapy response of undifferentiated nasopharyngeal carcinoma

“…al. 10 showed significant differences between strong cyclin D1 expression in the sensitive radiotherapy response group and in the insensitive group (p<0.05). Patients with weak cyclin D1 expression are more sensitive to radiation.…”

“…Radiation-induced DNA damage can also activates cyclin D1 to assist the process of DNA repair, thus increasing tumor cell survival and results in resistance to radiotherapy. 10 Cyclin D1 depletion in HeLa cervical carcinoma cells and H2009 lung cancer cells significantly increases the sensitivity of cancer cells to radiation. This suggests cyclin D1 to play a role in repairing damaged DNA.…”

“…The immunoexperpression assessment of cyclin D1 and VEGF using Histoscore determined based on the number of multiplication intensities and distributions with a weak expression if total score is 0-4 and strong expressions if total score 6-12. 10,13 The diagnosis was established by anatomic pathologist at the Department of Anatomic Pathology, Dr. Hasan Sadikin General Hospital, Bandung.…”

“…Cyclin D1 is a core protein that bound to CDK4/CDK6 forming the D1-CDK4/6 cyclin complex, which is involved in the phosphorylation of retinoblastoma proteins (pRb) in the G1 and S cell cycle phases and plays an important role in assisting cellular DNA repair. 10 Radioresistance of tumor cells is also associated with angiogenesis process. Rapid tumor growth can lead to hypoxia so that tumor cells will initiate survival mechanism by activating vascular endothelial growth factor (VEGF), which causes increased vascular proliferation and angiogenesis.…”

“…The VEGF is an angiogenic protein that plays a role in the growth of endothelial cells and tumor blood vessels. 10,11 The aim of this study was to evaluate the association between expression of cyclin D1 and VEGF with radiotherapy response in undifferentiated nasopharyngeal carcinoma.…”