New tumor markers: CA125 and beyond.
ABSTRACT A variety of biomarkers have been developed to monitor growth of ovarian cancer and to detect disease at an early interval. CA125 (MUC16) has provided a useful serum tumor marker for monitoring response to chemotherapy, detecting disease recurrence, distinguishing malignant from benign pelvic masses, and potentially improving clinical trial design. A rapid fall in CA125 during chemotherapy predicts a favorable prognosis and could be used to redistribute patients on multiarmed randomized clinical trials. Several studies now document that CA125 can serve as a surrogate marker for response in phase II trials. Serial measurement of CA125 might also provide a useful marker for monitoring stabilization of disease with cytostatic targeted therapeutic agents. The greatest potential for serum markers may be in detecting ovarian cancer at an early stage. A rising CA125 can be used to trigger transvaginal sonography (TVS) in a small fraction of patients. An algorithm has been developed that calculates risk of ovarian cancer based on serial CA125 values and refers patients at highest risk for TVS. Use of the algorithm is currently being evaluated in a trial with 200,000 women in the UK that will test critically the ability of a two-stage screening strategy to improve survival in ovarian cancer. Whatever the outcome, as 20% of ovarian cancers have little or no expression of CA125, additional serum markers will be required to detect all patients in an initial phase of screening. More than 30 serum markers have been evaluated alone and in combination with CA125 by different investigators. Some of the most promising include: HE4, mesothelin, M-CSF, osteopontin, kallikrein(s), and soluble EGF receptor. Two proteomic approaches have been used: one examines the pattern of peaks on mass spectroscopy and the other uses proteomic analysis to identify a limited number of critical markers that can be assayed by more conventional methods. Both approaches are promising and require further development. Several groups are placing markers on multiplex platforms to permit simultaneous assay of multiple markers with very small volumes of serum. Mathematical techniques are being developed to analyze combinations of marker levels to improve sensitivity and specificity. In the future, serum markers should improve the sensitivity of detecting recurrent disease as well as facilitate earlier detection of ovarian cancer.
- SourceAvailable from: PubMed Central[Show abstract] [Hide abstract]
ABSTRACT: A combination of peptide ligand library beads (PLLB) and 1D gel liquid chromatography-mass spectrometry/mass spectrometry (1DGel-LC-MS/MS) was employed to analyze serum samples from patients with ovarian cancer and from healthy controls. Proteomic analysis identified 1200 serum proteins, among which 57 proteins were upregulated and 10 were downregulated in the sera from cancer patients. Retinol binding protein 4 (RBP4) is highly upregulated in the ovarian cancer serum samples. ELISA was employed to measure plasma concentrations of RBP4 in 80 samples from ovarian cancer patients, healthy individuals, myoma patients, and patients with benign ovarian tumor, respectively. The plasma concentrations of RBP4 ranging from 76.91 to 120.08 ng/mL with the mean value 89.13 ± 1.67 ng/mL in ovarian cancer patients are significantly higher than those in healthy individuals (10.85 ± 2.38 ng/mL). Results were further confirmed with immunohistochemistry, demonstrating that RBP4 expression levels in normal ovarian tissue were lower than those in ovarian cancer tissues. Our results suggested that RBP4 is a potential biomarker for diagnostic of screening ovarian cancer.BioMed Research International 01/2014; 2014:179040. · 2.71 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: CA125, a tumor-associated antigen, is primarily used to monitor epithelial ovarian cancer. There is evidence that different species of CA125 exist; however, it is not known if any of these species are present in healthy women during the menstrual cycle and if they are associated with serum concentrations of CA125. The purpose of this study was to determine if the molecular species of CA125 differ across the three phases of the menstrual cycle in healthy women. Healthy, Caucasian women between the ages of 18 and 39 were enrolled using strict criteria to exclude factors known to contribute to CA125 fluctuations. Menstrual cycle regularity was determined using calendars maintained by participants for 3 months. After cycle regularity was established, blood was drawn at three time points for Western blot analysis. Western blot analysis yielded 17 distinct profiles (i.e., patterns of species) of CA125, with 80% of the sample exhibiting 5 common profiles. No differences in demographic characteristics and serum CA125 values were found among the various CA125 profiles. Different molecular species of CA125 exist in healthy women with regular menstrual cycles. These data provide evidence that CA125 is not a homogeneous molecular species. Future research should evaluate the molecular composition and the clinical importance of these species. © The Author(s) 2015.Biological Research for Nursing 01/2015; · 1.34 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: MUC16 is a high-molecular-weight glycoprotein that is expressed by the various epithelial cell surfaces of the human body to protect the cell layer from a myriad of insults. It is the largest mucin known to date, with an ∼22,152 aa sequence. Structurally, MUC16 is characterized into 3 distinct domains: the amino terminal, the tandem repeat, and the carboxyl terminal domain, with each domain having unique attributes. The extracellular portion of MUC16 is shed into the bloodstream and serves as a biomarker for diagnosing and monitoring patients with cancer; however, its functional role in cancer is yet to be elucidated. Several factors contribute to this challenge, which include the large protein size; the extensive glycosylation that the protein undergoes, which confers functional heterogeneity; lack of specific antibodies that detect the unique domains of MUC16; and the existence of splicing variants. Despite these limitations, MUC16 has been established as a molecule of significant application in cancer. Hence, in this review, we discuss the various aspects of MUC16, which include its discovery, structure, and biological significance both in benign and malignant conditions with an attempt to dissect its functional relevance.-Haridas, D., Ponnusamy, M. P., Chugh, S., Lakshmanan, I., Seshacharyulu, P., and Batra, S. K. MUC16: molecular analysis and its functional implications in benign and malignant conditions.The FASEB Journal 07/2014; · 5.48 Impact Factor