Methods and kits to detect and monitor ovarian cancer and preeclampsia
The present invention provides methods and kits related to a prognostic, and, in certain embodiments, diagnostic indicator for ovarian cancer which comprises measuring the level of MUC16 bound to immune cells. The level of MUC16 bound to immune cells can by itself be an indicator of disease regression or recurrence, or this indicator can be used in conjunction with assays for serum CA125 and other diagnostic markers. The invention further provides methods and kits related to the detection of ovarian cancer by measuring levels of Siglec-9 expression on immune cells. As well, related methodologies are provided for the detection of preeclampsia in pregnant human subjects.
1. A method to detect ovarian cancer in a subject, comprising:
(a) obtaining a sample of immune cells from a subject, wherein the immune cells are selected from Siglec-9 expressing natural killer cells, B cells, monocytes, neutrophils, or mixtures thereof contained within the sample; and
(b) measuring said sample of immune cells from the subject for binding of MUC16 to natural killer cell subsets CD16 pos /CD56 dim and CD16 neg /CD56 bright present in the immune cells contained within the sample in order to obtain a distribution of MUC16 between said subsets, wherein an elevated level of MUC16 bound to the CD16 pos /CD56 dim subset as compared to the CD16 neg /CD56 bright subset indicates ovarian cancer in the subject.
2. The method according to claim 1 , wherein the sample is a peripheral blood, peritoneal fluid, or tissue sample.
3. The method according to claim 1 , wherein an antibody specific for MUC16 is used to measure the level of MUC16 bound to the immune cells.
4. The method according to claim 3 , wherein measuring the level of MUC16 bound to the immune cells is performed by flow cytometry detection of the antibody specific for MUC16.
5. The method according to claim 3 , wherein the measuring step is carried out by radioisotopic, enzymatic, fluorogenic, chemiluminescent, or electrochemical detection of an immune complex comprising the antibody specific for MUC16 and MUC16 bound to the immune cells.
6. The method according to claim 1 , wherein said method is repeated at least once with said subject in order to monitor the progress of ovarian cancer in the subject.
7. The method according to claim 1 , wherein the level of MUC16 bound to the CD16 pos /CD56 dim subset is elevated by at least 2 fold as compared to the CD16 neg /CD56 bright subset.
8. A method to detect preeclampsia in a pregnant subject, comprising:
(a) obtaining an immune cell sample from a pregnant subject; and
(b) measuring binding of MUC16 to natural killer cell subsets CD16 pos /CD56 dim and CD16 neg /CD56 bright contained within the immune cell sample in order to obtain a distribution of MUC16 between said subsets, wherein a higher level of MUC16 bound to the CD16 neg /CD56 bright subset as compared to the CD16 pos /CD56 dim subset indicates preeclampsia in said pregnant subject.
9. The method according to claim 8 , wherein the immune cell sample is a peripheral blood sample.
10. The method according to claim 8 , wherein the level of MUC16 bound to the CD16 neg /CD56 bright subset is at least 2 fold higher than the MUC16 bound to the CD16 pos /CD56 dim subset.