JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE) ›› 2021, Vol. 41 ›› Issue (1): 118-122.doi: 10.3969/j.issn.1674-8115.2021.01.022

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Expression of breast cancer susceptibility gene 1 protein in brain gliomas and its influence on the sensitivity of temozolomide

Xiao-jun ZHAO1(), Zhi-gang QIAO1, Ting-yu LIANG1, Yan-ling AN2()   

  1. 1.Department of Neurosurgery, Shanxi Provincial Cancer Hospital, Taiyuan 030013, China
    2.College of Nursing, Shanxi Health Vocational College, Taiyuan 030619, China
  • Online:2021-01-28 Published:2021-02-22
  • Contact: Yan-ling AN E-mail:1785486946@qq.com;ayl1973ayl@163.com

Abstract: Objective

·To investigate the expression of breast cancer susceptibility gene 1 (BRCA1) protein in brain glioma tissue and its influence on the sensitivity of temozolomide (TMZ).

Methods

·A total of 104 patients with brain glioma (study group) who underwent surgical resection in the Department of Neurosurgery, Shanxi Provincial Cancer Hospital from January 2010 to December 2017 were collected. And 30 patients with head injury (control group) who underwent internal decompression surgery were collected. The BRCA1 protein expressions in brain tissues of the two groups were detected by immunohistochemistry. The relationship between BRCA1 protein expression and the clinicopathological characteristics of brain glioma patients was analyzed by χ2 test. The survival rate of the glioma patients with BRCA1 protein positive or negative expression was calculated by Kaplan-Meier method, and the difference between the positive patients and the negative patients was tested by Log-Rank method. The U251 cells were randomly divided into three groups, and transfected with shRNA-BRCA1 silencing vector (sh-BRCA1 group), shNC-BRCA1 empty expression vector (sh-NC group) and blank control phosphate buffer saline (Blank group), respectively. The transfection efficiency of the three groups was detected by quantitative PCR (qPCR). CCK-8 method was used to detect proliferative activity of U251 cells in the three groups and the sensitivity of TMZ.

Results

·Immunohistochemistry showed that 23 of the 30 control tissues were BRCA1 positive, with a positive expression rate of 76.67%, while 33 of the 104 glioma tissues were positive, with a positive expression rate of 31.73%; the difference in the positive expression rates between the two groups was statistically significant (P=0.009). In the study group, the expression of BRCA1 protein in the tumor tissues with pathological grade Ⅰ~Ⅱ was significantly higher than that in the tumor tissues with pathological grade Ⅲ~Ⅳ (P=0.022), and there was no significant correlation between BRCA1 protein expression and the patient's age, gender and pathological type. There was no significant difference in the survival rates between BRCA1 positive and negative patients. The results of in vitro studies showed that the BRCA1 mRNA expression level in the sh-BRCA1 group was significantly lower than those in the sh-NC group (P=0.037) and the Blank group (P=0.035). After transfection and 48 and 72 h of cell culture, the cell proliferation activity of the sh-BRCA1 group was higher than those of the Blank group (P=0.043, P=0.037) and the sh-NC group (P=0.046, P=0.037); when the TMZ concentration was 100 and 200 μmol/L, the cell proliferation activity of the sh-BRAC1 group was higher than those of the sh-NC group (P=0.041, P=0.040) and the Blank group (P=0.038, P=0.042).

Conclusion

·BRCA1 protein is lower expressed in brain glioma, and the positive expression of BRCA1 is related to the tumor pathological grade, but not related to the patient's age, gender, pathological type and survival rate. Inhibition of BRCA1 expression can reduce the sensitivity of brain glioma cells to TMZ.

Key words: brain glioma, breast cancer susceptibility gene 1 (BRCA1), temozolomide (TMZ), survival rate, drug sensitivity

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