Identification of cancer protein biomarkers using proteomic techniques
AssigneeYale University
InventorsGil G. Mor, David C. Ward, Patricia Bray-Ward
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Abstract
The claimed invention describes methods to diagnose or aid in the diagnosis of cancer. The claimed methods are based on the identification of biomarkers which are particularly well suited to discriminate between cancer subjects and healthy subjects. These biomarkers were identified using a unique and novel screening method described herein. The biomarkers identified herein can also be used in the prognosis and monitoring of cancer. The invention comprises the use of leptin, prolactin, OPN and IGF-II for diagnosing, prognosis and monitoring of ovarian cancer.
Claims32
A method for diagnosing or aiding in the diagnosis of ovarian cancer in a subject comprising;
- (a) measuring the expression levels of four or more biomarkers in a sample from a subject, wherein four of the biomarkers are prolactin, osteopontin (OPN), leptin, and insulin-like growth factor II (IGF-II);
- (b) comparing the expression level of prolactin, OPN, leptin, and IGF-II to a predetermined standard for prolactin, OPN, leptin, and IGF-II, respectively, wherein a significant difference in the expression level of two or more of the prolactin, OPN, leptin, and IGF-II biomarkers in the sample as compared to a predetermined standard for each of the prolactin, OPN, leptin, and IGF-II biomarkers diagnoses or aids in the diagnosis of ovarian cancer, and wherein a significant difference in the expression level for prolactin or OPN is an increase in the expression level of prolactin or OPN compared to the predetermined standards for prolactin and OPN, respectively;
- and a significant difference in the expression level for leptin or IGF-II is a decrease in the level of expression of leptin or IGF-II compared to the predetermined standards for leptin and IGF-II, respectively.
A method of monitoring the progression of ovarian cancer in a subject comprising
- (a) measuring the expression levels of four or more biomarkers in a first sample from the subject and a subsequent sample from the subject, wherein four of the biomarkers are prolactin, osteopontin (OPN), leptin, and insulin-like growth factor II (IGF-II);
- (b) comparing the expression of the prolactin, OPN, Leptin, and IGF-II biomarkers in the first sample to the expression of the prolactin, OPN, leptin, and IGF-II biomarkers in the subsequent sample wherein a significant difference in the expression level of two or more of the prolactin, OPN, leptin, and IGF-II biomarkers in a sample as compared to a predetermined standard for each of the prolactin, OPN, leptin, and IGF-II biomarkers, and a significant difference for prolactin or OPN is an increase in the level of prolactin or OPN compared to the predetermined standards for prolactin and OPN, respectively;
- and a significant difference for leptin or IGF-II is a decrease in the level of leptin or IGF-II compared to the predetermined standards for leptin and IGF-II, respectively, and wherein an increase in the number of significantly different expression levels of the prolactin, OPN, letin, and IGF-II biomarkers in the first sample compared to the subsequent sample indicates progression of ovarian cancer in the subject and a decrease in the number of significantly different expression levels of the prolactin, OPN, leptin, and IGF-II biomarkers in the first sample compared to the subsequent sample indicates regression of ovarian cancer in the subject.
A method for diagnosing or aiding in the diagnosis of ovarian cancer in a subject comprising;
- (a) measuring the expression levels of four or more biomarkers in a sample from a subject, wherein the four biomarkers are prolactin, osteopontin (OPN), leptin, and insulin-like growth factor II (LOP-II);
- (b) comparing the expression level of prolactin to a prolactin split point, wherein if the prolactin expression level for the subject is below the prolactin split point, a score corresponding to healthy is assigned and if the prolactin expression level is at or above the prolactin split point, a score corresponding to cancer is assigned;
- (c) comparing the expression level of OPN to an OPN split point, wherein if the OPN expression level for the subject is below the OPN split point, a score corresponding to healthy is assigned and if the OPN expression level is at or above the OPN split point a score corresponding to cancer is assigned;
- (d) comparing the expression level of leptin to a leptin split point, wherein if the leptin expression level is below the leptin split point a score corresponding to cancer is assigned and if the leptin expression level is at or above the leptin split point a score corresponding to healthy is assigned;
- (e) comparing the expression level of IGF-II to an IGF-II split point, wherein if the IGF-II expression level is below the IGF-II split point, a score corresponding to cancer is assigned and if the IGF-II expression level is at or above the IGF-II split point, a score corresponding to healthy is assigned;
- (f) calculating the total number of scores corresponding to cancer for the prolactin, OPN, leptin, and IGF-II biomarkers whose expression levels in the sample were determined and comparing the total number of scores corresponding to cancer with a predetermined score (t), wherein a total number of scores corresponding to cancer greater than (t) diagnoses or aids in the diagnosis of ovarian cancer in the subject;
- and
- (g) determining the diagnosis or aiding in determining the diagnosis of ovarian cancer in the subject based on the calculation of the total number of scores corresponding to cancer for the prolactin, OPN, Leptin, and IGF-II biomarkers.
A method of monitoring the progression of ovarian cancer in a subject comprising:
- (a) measuring the expression levels of four or more biomarkers in a first sample from the subject and a subsequent sample from the subject, wherein four of the four or more biomarkers are prolactin, osteopontin (OPN), leptin, and insulin-like growth factor II (IGF-II);
- (b) comparing the expression level of prolactin in each sample to a prolactin split point, wherein if the prolactin expression level for a sample is below the prolactin split point, a score corresponding to healthy is assigned to that sample and if the prolactin expression level for a sample is at or above the prolactin split point, a score corresponding to cancer is assigned to that sample;
- (c) comparing the expression level of OPN in a sample to an OPN split point, wherein if the OPN expression level for either sample is below the OPN split point, a score corresponding to healthy is assigned to that sample and if the OPN expression level for a sample is at or above the OPN split point, a score corresponding to cancer is assigned to that sample;
- (d) comparing the expression level of leptin in a sample to a leptin split point, wherein if the leptin expression level for a sample is below the leptin split point, a score corresponding to cancer is assigned to that sample and if the leptin expression level for a sample is at or above the leptin split point, a score corresponding to healthy is assigned to that sample;
- (e) comparing the expression level of IGF-II in each sample to an IGF-II split point, wherein if the IGF-II expression level for a sample is below the IGF-II split point, a score corresponding to cancer is assigned to that sample and if the IGF-II expression level for a sample is at or above the IGF-II split point, a score corresponding to healthy is assigned to that sample;
- (f) calculating the total number of scores for each sample corresponding to cancer for the prolactin, OPN, leptin, and IGF-II biomarkers whose expression levels in the samples were determined;
- and
- (g) comparing each sample's total number scores corresponding to cancer, wherein a difference in the total number of scores between the first and subsequent samples monitors the progression of the ovarian cancer in the subject.
Dependencies are inferred from the claim text.