Open AccessComprehensive analysis of serum tumor markers and BRCA1/2 germline mutations in Chinese ovarian cancer patients
Author(s) -
Deng Hongyu,
Chen Ming,
Guo Xinwu,
Heng Jianfu,
Xu Xunxun,
Peng Limin,
Jiang Hui,
Li Guoli,
Day Julia X.,
Li Jinliang,
Shan Dongyong,
Li Yinghua,
Zhou Yanjie,
Liu Bin,
Dai Lizhong,
Wang Xiaochun,
Wang Jun
Publication year - 2019
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.672
Subject(s) - ovarian cancer , germline mutation , germline , breast cancer , cancer , medicine , oncology , sanger sequencing , ovarian tumor , cancer research , mutation , biology , genetics , gene
Background The serum tumor markers has been widely used in ovarian cancer diagnosis. BRCA1/2 germline mutations are the most common predisposing factors for ovarian cancer development. This study aimed to comprehensively investigate serum tumor markers and BRCA1/2 germline mutations and analyze their associations with ovarian cancer. Methods Levels of 11 serum tumor markers were examined in ovarian cancer patients and controls with benign gynecologic diseases. By integrating multiplex PCR and next‐generation sequencing technologies, BRCA1/2 germline mutations were analyzed and confirmed by Sanger sequencing. The discriminative models with serum tumor markers and BRCA1/2 mutation status were constructed for ovarian cancer detection and patient stratification. Results Among 11 markers, six of them were significantly elevated and only beta‐human chorionic gonadotropin (β‐HCG) was significantly reduced in ovarian cancer patients. A total of 54 (23.3%) ovarian cancer patients were found to harbor BRCA1/2 deleterious mutations, and BRCA1/2 mutations were significantly associated with Hereditary Breast and Ovarian Cancer‐related tumors and family history of cancer. Carbohydrate antigen 125 showed a good performance in ovarian cancer detection as a single marker (AUC = 0.799), while a panel of eight markers showed a good performance in BRCA1 mutation detection with an AUC value of 0.974. In addition, a panel of five serum tumor markers combined with BRCA1/2 mutation status showed a good performance in lymph node metastasis prediction (AUC = 0.843). Conclusions We found the association between BRCA1/2 germline mutation status and serum tumor marker levels, and identified discriminative models that combined serum tumor markers with BRCA1/2 mutation status for ovarian cancer detection and patient stratification.