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

被引:17
作者
Zhang, Zhengmao [1 ]
Dou, Xiaomeng [1 ]
Yang, Hongfang [2 ]
Jia, Ling [1 ]
Qin, Kaiyun [3 ]
Gao, Xingshuang [3 ]
Yang, Botao [1 ]
Zhang, Wenzhe [4 ]
Qin, Congying [1 ]
Zhang, Fenghua [5 ]
Shan, Baoen [6 ]
机构
[1] Hebei Med Univ, Hosp 4, Dept Gynaecol, Shijiazhuang 050011, Peoples R China
[2] Hebei Med Univ, Hosp 4, Dept Lab Med, Shijiazhuang 050011, Peoples R China
[3] Hebei Gen Hosp, Dept Gynaecol, Shijiazhuang 050051, Peoples R China
[4] Hebei Med Univ, Hosp 4, Dept Gynaecol & VIP, Shijiazhuang 050011, Peoples R China
[5] Hebei Gen Hosp, Dept Gen Surg, Shijiazhuang 050051, Peoples R China
[6] Hebei Med Univ, Hosp 4, Dept Res Ctr, 12 Jiankang Rd, Shijiazhuang 050011, Peoples R China
关键词
Ovarian cancer; p53; Livin; Chemo-Resistance; Prognosis; DNA-REPAIR; POLY(ADP-RIBOSE) POLYMERASE-1; PLATINUM RESISTANCE; PROTEIN EXPRESSION; APOPTOSIS PROTEIN; EXCISION-REPAIR; SURVIVAL; CHEMOTHERAPY; INHIBITOR; MUTATIONS;
D O I
10.1016/j.prp.2019.152794
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
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.
引用
收藏
页数:8
相关论文
共 51 条
[1]   The Inhibitor of Apoptosis Protein Livin (ML-IAP) Plays a Dual Role in Tumorigenicity [J].
Abd-Elrahman, Ihab ;
Hershko, Klilah ;
Neuman, Tzahi ;
Nachmias, Boaz ;
Perlman, Riki ;
Ben-Yehuda, Dina .
CANCER RESEARCH, 2009, 69 (13) :5475-5480
[2]   The biology of ovarian cancer: new opportunities for translation [J].
Bast, Robert C., Jr. ;
Hennessy, Bryan ;
Mills, Gordon B. .
NATURE REVIEWS CANCER, 2009, 9 (06) :415-428
[3]   Evaluation of New Platinum-Based Treatment Regimens in Advanced-Stage Ovarian Cancer: A Phase III Trial of the Gynecologic Cancer InterGroup [J].
Bookman, Michael A. ;
Brady, Mark F. ;
McGuire, William P. ;
Harper, Peter G. ;
Alberts, David S. ;
Friedlander, Michael ;
Colombo, Nicoletta ;
Fowler, Jeffrey M. ;
Argenta, Peter A. ;
De Geest, Koen ;
Mutch, David G. ;
Burger, Robert A. ;
Swart, Ann Marie ;
Trimble, Edward L. ;
Accario-Winslow, Chrisann ;
Roth, Lawrence M. .
JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (09) :1419-1425
[4]  
Bottini A, 2000, CLIN CANCER RES, V6, P2751
[5]   Clinicopathologic features of BRCA-linked and sporadic ovarian cancer [J].
Boyd, J ;
Sonoda, Y ;
Federici, MG ;
Bogomolniy, F ;
Rhei, E ;
Maresco, DL ;
Saigo, PE ;
Almadrones, LA ;
Barakat, RR ;
Brown, CL ;
Chi, DS ;
Curtin, JP ;
Poynor, EA ;
Hoskins, WJ .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2000, 283 (17) :2260-2265
[6]   Cancer of the ovary [J].
Cannistra, SA .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 351 (24) :2519-2529
[7]   BRCA1 is both a prognostic and predictive biomarker of response to chemotherapy in sporadic epithelial ovarian cancer [J].
Carser, Judith E. ;
Quinn, Jennifer E. ;
Michie, Caroline O. ;
O'Brien, Eamonn J. ;
McCluggage, W. Glenn ;
Maxwell, Perry ;
Lamers, Elisabeth ;
Lioe, Tong F. ;
Williams, Alistair R. W. ;
Kennedy, Richard D. ;
Gourley, Charlie ;
Harkin, D. Paul .
GYNECOLOGIC ONCOLOGY, 2011, 123 (03) :492-498
[8]   Livin/melanoma inhibitor of apoptosis protein as a potential therapeutic target for the treatment of malignancy [J].
Chang, Hong ;
Schimmer, Aaron D. .
MOLECULAR CANCER THERAPEUTICS, 2007, 6 (01) :24-30
[9]   A longitudinal analysis with CA-125 to predict overall survival in patients with ovarian cancer [J].
Chiang, An Jen ;
Chen, Jiabin ;
Chung, Yu-He ;
Huang, Huan-Jung ;
Liou, Wen Shiung ;
Chang, Chung .
JOURNAL OF GYNECOLOGIC ONCOLOGY, 2014, 25 (01) :51-57
[10]   Translational research in the Gynecologic Oncology Group: Evaluation of ovarian cancer markers, profiles, and novel therapies [J].
Darcy, Kathleen M. ;
Birrer, Michael J. .
GYNECOLOGIC ONCOLOGY, 2010, 117 (03) :429-439