Comprehensive analysis of serum tumor markers and BRCA1/2 germline mutations in Chinese ovarian cancer patients

Abstract

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.

Identification of BRCA1:c.5470_5477del as a Founder Mutation in Chinese Ovarian Cancer Patients

“…( 12 , 19 – 21 ); this is probably caused by the different ethnic origins and geographic locations of the included patients. Several studies have reported the BRCA1 :c.5470_5477del as the most frequently detected mutation in Chinese OC patients; of note, the patients enrolled in these studies were mainly from northern China ( 13 , 20 , 22 ), and studies on the southern Chinese revealed different top mutations ( 12 , 19 , 21 ). In this study, almost all the patients are from Henan, the central region of China and the origin of Chinese civilization.…”

Evaluating the role of wound‐healing genes in conjunction with stool routine and serum tumor markers for colorectal cancer diagnosis and prognostic implications

“…With the continuous advancement of molecular biology technology, the detection of serum tumour markers has gradually been applied in clinical practice. It has become a milestone in medical science and has safety advantages, non‐invasiveness and simple sampling 19,20 . Carcinoembryonic antigen (CEA), 5 sugar chain antigen 19–9 (CA199) 6 and CA125 7 are commonly used clinical tumour markers and have been proven to have application value in various malignant tumours.…”

<p>Prognostic Significance of Log(CA125)/PCI for the Resectability of Epithelial Ovarian Cancer: A Retrospective Study</p>

“…Tumor markers are not only used in screening ovarian cancer; some studies found that CA125 showed good performance in ovarian cancer with BRCA1/2 mutation detection as a single marker (AUC=0.799). 11 This reminded us that tumor markers may represent the characteristics to some degree. Unfortunately, our results suggested that CA125, the most commonly used tumor marker in ovarian cancer, had no significant effect on survival or on the outcomes of PDS.…”