Autoimmune response to PARP and BRCA1/BRCA2 in cancer

被引:19
作者
Zhu, Qing [1 ,2 ]
Han, Su-Xia [1 ]
Zhou, Cong-Ya [1 ]
Cai, Meng-Jiao [1 ]
Dai, Li-Ping [2 ]
Zhang, Jian-Ying [2 ]
机构
[1] Xi An Jiao Tong Univ, Med Ctr, Dept Oncol, Affiliated Hosp 1, Xian 710049, Shaanxi, Peoples R China
[2] Univ Texas El Paso, Dept Biol Sci, El Paso, TX 79968 USA
基金
美国国家卫生研究院; 中国国家自然科学基金;
关键词
autoantibody; DNA repair enzyme poly (ADP-Ribose) polymerase 1 (PARP1)/BRCA1/BRCA2; synthetic lethality; tumor-associated antigen (TAA); autoimmune; TUMOR-ASSOCIATED ANTIGENS; SYNTHETIC LETHALITY; ANTIBODY DETECTION; AUTOANTIBODIES; BIOMARKERS; MECHANISMS; RESISTANCE; REPORTERS; CELLS;
D O I
10.18632/oncotarget.3428
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: To determine the role of autoantibodies to PARP1 and BRCA1/BRCA2 which were involved in the synthetic lethal interaction in cancer. Methods: Enzyme-Linked Immunosorbent Assay (ELISA) was used to detect autoantibodies to PARP1 and BRCA1/BRCA2 in 618 serum samples including 131 from breast cancer, 94 from lung cancer, 34 from ovarian cancer, 107 from prostate cancer, 76 from liver cancer, 41 from pancreatic cancer and 135 from normal individuals. The positive sera with ELISA were confirmed by Western blot. Immunohistochemistry was used to examine the expression of PARP1 and BRCA1/BRCA2 in breast cancer. Results: Autoantibody frequency to PARP1, BRCA1, and BRCA2 in cancer varied from 0% to 50%. When the sera from cancer patients were tested for the presence of autoantibodies to PARP1 and BRCA1/BRCA2, the autoantibody responses slightly decreased and the positive autoantibody reactions varied from 0% to 50.0%. This was significantly higher autoantibody responses to PARP1 and BRCA1/BRCA2 (especially to PARP1 and BRCA1) in ovarian cancer and breast cancer compared to normal control sera (P < 0.001 and P < 0.01). Immunohistochemistry indicated that Pathology Grade at diagnosis to PARP1 expression in breast cancer was different (P < 0.05). Conclusions: Different cancers have different profiles of autoantibodies. The autoantibodies to proteins involving the synthetic lethal interactions would be novel serological biomarker in some selective cancers.
引用
收藏
页码:11575 / 11584
页数:10
相关论文
共 33 条
[1]   Influence of Chemotherapy on EGFR Mutation Status Among Patients With Non-Small-Cell Lung Cancer [J].
Bai, Hua ;
Wang, Zhijie ;
Chen, Keneng ;
Zhao, Jun ;
Lee, J. Jack ;
Wang, Shuhang ;
Zhou, Qinghua ;
Zhuo, Minglei ;
Mao, Li ;
An, Tongtong ;
Duan, Jianchun ;
Yang, Lu ;
Wu, Meina ;
Liang, Zhen ;
Wang, Yuyan ;
Kang, Xiaozheng ;
Wang, Jie .
JOURNAL OF CLINICAL ONCOLOGY, 2012, 30 (25) :3077-3083
[2]   Genome-wide Profiling of Genetic Synthetic Lethality Identifies CDK12 as a Novel Determinant of PARP1/2 Inhibitor Sensitivity [J].
Bajrami, Ilirjana ;
Frankum, Jessica R. ;
Konde, Asha ;
Miller, Rowan E. ;
Rehman, Farah L. ;
Brough, Rachel ;
Campbell, James ;
Sims, David ;
Rafiq, Rumana ;
Hooper, Sean ;
Chen, Lina ;
Kozarewa, Iwanka ;
Assiotis, Ioannis ;
Fenwick, Kerry ;
Natrajan, Rachael ;
Lord, Christopher J. ;
Ashworth, Alan .
CANCER RESEARCH, 2014, 74 (01) :287-297
[3]   Searching for synthetic lethality in cancer [J].
Brough, Rachel ;
Frankum, Jessica R. ;
Costa-Cabral, Sara ;
Lord, Christopher J. ;
Ashworth, Alan .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 2011, 21 (01) :34-41
[4]   Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase [J].
Bryant, HE ;
Schultz, N ;
Thomas, HD ;
Parker, KM ;
Flower, D ;
Lopez, E ;
Kyle, S ;
Meuth, M ;
Curtin, NJ ;
Helleday, T .
NATURE, 2005, 434 (7035) :913-917
[5]   Autoantibodies to tumor-associated antigens combined with abnormal alpha-fetoprotein enhance immunodiagnosis of hepatocellular carcinoma [J].
Chen, Yao ;
Zhou, Yusen ;
Qiu, Suimin ;
Wang, Kaijuan ;
Liu, Siwei ;
Peng, Xuan-Xian ;
Li, Junfeng ;
Tan, Eng M. ;
Zhang, Jian-Ying .
CANCER LETTERS, 2010, 289 (01) :32-39
[6]   Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy [J].
Farmer, H ;
McCabe, N ;
Lord, CJ ;
Tutt, ANJ ;
Johnson, DA ;
Richardson, TB ;
Santarosa, M ;
Dillon, KJ ;
Hickson, I ;
Knights, C ;
Martin, NMB ;
Jackson, SP ;
Smith, GCM ;
Ashworth, A .
NATURE, 2005, 434 (7035) :917-921
[7]   Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing [J].
Gerlinger, Marco ;
Rowan, Andrew J. ;
Horswell, Stuart ;
Larkin, James ;
Endesfelder, David ;
Gronroos, Eva ;
Martinez, Pierre ;
Matthews, Nicholas ;
Stewart, Aengus ;
Tarpey, Patrick ;
Varela, Ignacio ;
Phillimore, Benjamin ;
Begum, Sharmin ;
McDonald, Neil Q. ;
Butler, Adam ;
Jones, David ;
Raine, Keiran ;
Latimer, Calli ;
Santos, Claudio R. ;
Nohadani, Mahrokh ;
Eklund, Aron C. ;
Spencer-Dene, Bradley ;
Clark, Graham ;
Pickering, Lisa ;
Stamp, Gordon ;
Gore, Martin ;
Szallasi, Zoltan ;
Downward, Julian ;
Futreal, P. Andrew ;
Swanton, Charles .
NEW ENGLAND JOURNAL OF MEDICINE, 2012, 366 (10) :883-892
[8]   Hallmarks of Cancer: The Next Generation [J].
Hanahan, Douglas ;
Weinberg, Robert A. .
CELL, 2011, 144 (05) :646-674
[9]   The concept of synthetic lethality in the context of anticancer therapy [J].
Kaelin, WG .
NATURE REVIEWS CANCER, 2005, 5 (09) :689-698
[10]  
Koziol JA, 2003, CLIN CANCER RES, V9, P5120