Association of expression of p53, livin, ERCC1, BRCA1 and PARP1 in epithelial ovarian cancer tissue with drug resistance and prognosis.

Abstract

OBJECTIVE:

To evaluate the correlation between expression of p53, Livin, Excision repair cross-complementation group 1 (ERCC1), BRCA1 and Poly (ADP-ribose) polymerase 1 (PARP 1) in epithelial ovarian cancer (EOC) tissues with platinum-based chemotherapy and prognosis in patients who received either comprehensive surgical staging or cytoreductive surgery.

METHODS:

The protein expressions level of five potential regulators involved in chemo-resistance, including p53, Livin, ERCC1, BRCA1 and PARP1 in EOC tissues from 66 patients were evaluated using immunohistochemistry method. We also measured preoperative CA125 level measured by an electrochemiluminescence immunoassay (ECLIA) in all patients. Cox proportional hazard regression model was established to identify whether these proteins are associated with overall survival.

RESULTS:

Chemo-resistance and poor overall survival were shown to be significantly related with positive expressions of p53, Livin, ERCC1, BRCA1 and PARP1. The evaluation of risk factors on the chemo-resistance showed that ERCC1 and BRCA1 are strong risk factors (OR: 21.12 and 21.61, all P < 0.01), while the positive expression of ERCC1, BRCA1 and PARP1 was significantly highly associated with the overall survival (HR: 3.9, 3.7 and 2.6, all P < 0.05, respectively). CA125 levels were significantly higher in patients with positive expression of P53, BRCA1, ERCC1 or Livin compared with those with negative expression (471:146, 667:260, 494:261 and 4589:89 U/ml, respectively, all P < 0.05).

CONCLUSIONS:

The elevated expression levels of ERCC1 and BRCA1 were identified as significant risk factors for chemo-resistance in EOC. Reduced expression levels of ERCC1, BRCA1 and PARP1 were significantly associated with better overall survival. The CA125 levels were significantly higher in patients with EOC specimens that were positive of p53, BRCA1, ERCC1 and Livin.

• Authors: Zhengmao Zhang, Xiaomeng Dou, Hongfang Yang, Ling Jia, Kaiyun Qin, Xingshuang Gao, Botao Yang, Wenzhe Zhang, Congying Qin, Fenghua Zhang, Baoen Shan
• Journal: Pathology, research and practice (Pathol Res Pract) Vol. 216 Issue 2 Pg. 152794 (Feb 2020) ISSN: 1618-0631 [Electronic] Germany
• PMID: 31902551 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier GmbH. All rights reserved.

Chemical References

• Adaptor Proteins, Signal Transducing
• BIRC7 protein, human
• BRCA1 Protein
• BRCA1 protein, human
• DNA-Binding Proteins
• Inhibitor of Apoptosis Proteins
• Neoplasm Proteins
• Tumor Suppressor Protein p53
• PARP1 protein, human
• Poly (ADP-Ribose) Polymerase-1
• ERCC1 protein, human
• Endonucleases

Topics

• Adaptor Proteins, Signal Transducing (metabolism)
• BRCA1 Protein (metabolism)
• Carcinoma, Ovarian Epithelial (diagnosis, drug therapy, metabolism)
• DNA-Binding Proteins (metabolism)
• Drug Resistance, Neoplasm
• Endonucleases (metabolism)
• Female
• Humans
• Inhibitor of Apoptosis Proteins (metabolism)
• Neoplasm Proteins (metabolism)
• Ovarian Neoplasms (diagnosis, drug therapy, metabolism)
• Poly (ADP-Ribose) Polymerase-1 (metabolism)
• Prognosis
• Tumor Suppressor Protein p53 (metabolism)