Detection and treatment of of early-stage ovarian cancer
A method of detecting serous ovarian cancer, particularly early stage serous ovarian cancer is described. The method uses up to sixteen compounds found in the blood serum of a person, and determines that changes of some portion of these sixteen compounds can determine the presence of serous ovarian cancer in a women with up to 100% accuracy, specificity, and sensitivity.
1. A method for detecting serous ovarian cancer comprising:
measuring in a serum sample the concentration of each of ten or more of serous OC metabolites 1 through 16 having neutral elemental formula(s) and identification as associated in Table 1; and
TABLE 1
Serum OC
Neutral
Metabolite
Elemental
No.
Formula
Metabolite Identification
1
C 42 H 80 N 3 O 30 ,
C 43 H 76 N 7 O 26 ,
C 42 H 76 N 9 O 25
2
C 27 H 51 O 12 P
Lysophatidylinositol (18:1)
3
C 9 H 18 O 3
2-hydroxyl nonanoic acid
4
C 34 H 67 NO 3
Ceramide (d18:1/16:0)
5
C 27 H 44 NO 7 P
Lysophosphatidylethanolamine (22:6)
6
C 24 H 46 O 2
7
C 9 H 13 N 2 O 7
aspartyl-glutamic acid
8
C 21 H 28 O 5
cortisone
9
C 27 H 42 O 4
10
C 32 H 60 O 6
16-(6-butoxy-3-hydroxy-4,5-
dimethylcyclohex-1-en-1-yl)-6,10-
dihydroxy-2,6,10,14-tetramethyl
hexadecanoic acid
11
C 28 H 52 O 5
7,9,13-trihydroxyoctacosa-16,22-
dienoic acid
12
C 47 H 81 O 13 P
Phosphatidylinositol (20:4/18:1)
13
C 40 H 68 N 6 O 17 ,
C 41 H 64 N 10 O 13 ,
C 40 H 64 N 12 O 12
14
C 18 H 36 O 2
iso-1,2-octadecanediol
15
C 7 H 14 O 2
16
C 12 H 22 O 5
3-hydroxyl dodecanedioic acid
evaluating the amount of change in the concentrations for at least one of the serous OC metabolites 1 through 16 versus control sample concentrations for the same at least one of the serous OC metabolites 1 through 16 in a control serum sample;
wherein an increase for metabolites 1 through 8 and a decrease for metabolites 9 through 16 indicates a positive result for serous ovarian cancer.
2. The method of claim 1 further comprising obtaining the serum sample;
wherein evaluating the amount of change in the concentrations comprises evaluating the amount of change in the concentrations for all of the serous OC metabolites 1 through 16 versus the control serum sample.
3. The method of claim 2 further comprising calibrating the method prior to a measurement of a serum sample or multiple serum samples;
wherein the calibration is conducted by testing a device with a calibration sample.
4. The method of claim 2 further comprising measuring the metabolite by ultra-performance liquid chromatography with a mass spectrometer as a detector.
5. The method of claim 4 , wherein measuring is conducted for 15 to 40 minutes.
6. The method of claim 4 , wherein measuring is conducted on a reverse phase column.
7. The method of claim 4 , wherein measuring is conducted using a water:alcohol gradient elution.
8. The method of claim 2 , wherein the 16 metabolites are separated using a C18 UPLC column with a methanol:water gradient elution; and
wherein the metabolites are measured by a MS detector.
9. The method of claim 2 , wherein the concentration of metabolites 1 through 8 increase by a log base 2 value of at least about 0.2 over the control serum sample.
10. The method of claim 2 , wherein the concentration of metabolites 10 through 16 decrease by a log base 2 value of at least about 0.15 versus the control serum sample.
11. The method of claim 2 , wherein each of the metabolites 1 through 16 are selected from the group consisting of cortisone, lysophatidylinositol (18:1), aspartyl-glutamic acid, 16-(6-butoxy-3-hydroxy-4,5-dimethylcyclohex-1-en-1-yl)-6,10-dihydroxy-2,6,10,14-tetramethyl hexadecanoicacid, ceramide, lysophosphatidylethanolamine (22:6), 2-hydroxyl nonanoic acid, iso-1,2-octadecanediol, 3-hydroxyl dodecanedioic acid, phosphatidylinositol (20:4/18:1), and 7,9,13-trihydroxyoctacosa-16,22-dienoic acid.
12. The method of claim 2 , wherein the serum sample is prepared by:
precipitating protein from a blood sample with methanol to make a supernatant and precipitate;
separating the protein from the supernatant by centrifugation;
mixing the supernatant with water and freeze drying the sample; and
reconstituting with a mobile phase solution at the time of analysis.
13. The method of claim 2 , wherein the control serum sample is a serum sample from a group of patients that do not have ovarian cancer.
14. A method for eliminating a patient's risk of late-stage serous ovarian cancer comprising:
collecting a serum sample during the patient's health examination;
measuring in the serum sample the concentration of each of ten or more of serous OC metabolites 1 through 16 having neutral elemental formula(s) and identification as associated in Table 1;
TABLE 1
Serum OC
Metabolite
No.
Neutral Elemental Formula
Metabolite Identification
1
C 42 H 80 N 3 O 30 , C 43 H 76 N 7 O 26 ,
C 42 H 76 N 9 O 25
2
C 27 H 51 O 12 P
Lysophatidylinositol (18:1)
3
C 9 H 18 O 3
2-hydroxyl nonanoic acid
4
C 34 H 67 NO 3
Ceramide (d18:1/16:0)
5
C 27 H 44 NO 7 P
Lysophosphatidyl-
ethanolamine (22:6)
6
C 24 H 46 O 2
7
C 9 H 13 N 2 O 7
aspartyl-glutamic acid
8
C 21 H 28 O 5
cortisone
9
C 27 H 42 O 4
10
C 32 H 60 O 6
16-(6-butoxy-3-hydroxy-4,5-
dimethylcyclohex-1-en-1-
yl)-6,10-dihydroxy-
2,6,10,14-tetramethyl
hexadecanoic acid
11
C 28 H 52 O 5
7,9,13-trihydroxyoctacosa-
16,22-dienoic acid
12
C 47 H 81 O 13 P
Phosphatidylinositol (20:4/18:1)
13
C 40 H 68 N 6 O 17 , C 41 H 64 N 10 O 13 ,
C 40 H 64 N 12 O 12
14
C 18 H 36 O 2
iso-1,2-octadecanediol
15
C 7 H 14 O 2
16
C 12 H 22 O 5
3-hydroxyl dodecanedioic acid
comparing the concentration of the serous OC metabolites 1 through 16 to the concentration of the same metabolites in an unaffected control serum sample to determine the presence or absence of serous ovarian cancer; and
prescribing a treatment regime for the patient.
15. The method of claim 14 further comprising calibrating the device prior to a measurement of a serum sample or multiple serum samples;
wherein the calibration is conducted by testing the device on a calibration sample.
16. The method of claim 14 , wherein the concentration of metabolites 1 through 8 increase by a log base 2 value of at least about 0.2 over the control serum sample.
17. The method of claim 14 , wherein the concentration of metabolites 10 through 16 decrease by a log base 2 value of at least about 0.15 versus the control serum sample.
18. A non-invasive method for treating serous ovarian cancer comprising identifying the presence of serous ovarian cancer in a patient; and
treating the patient with a cancer chemotherapy and/or radiation without resorting to invasive surgical exploration;
wherein identifying the presence of serous ovarian cancer comprises:
obtaining a serum sample from the patient;
measuring in the serum sample the concentration of serous OC metabolites 1 through 16 having neutral elemental formula(s) and identification as associated in Table 1; and
evaluating the change in the concentrations for the serous OC metabolites 1 through 16 versus a control serum sample;
TABLE 1
Serum OC
Metabolite
No.
Neutral Elemental Formula
Metabolite Identification
1
C 42 H 80 N 3 O 30 , C 43 H 76 N 7 O 26 ,
C 42 H 76 N 9 O 25
2
C 27 H 51 O 12 P
Lysophatidylinositol (18:1)
3
C 9 H 18 O 3
2-hydroxyl nonanoic acid
4
C 34 H 67 NO 3
Ceramide (d18:1/16:0)
5
C 27 H 44 NO 7 P
Lysophosphatidyl-
ethanolamine (22:6)
6
C 24 H 46 O 2
7
C 9 H 13 N 2 O 7
aspartyl-glutamic acid
8
C 21 H 28 O 5
cortisone
9
C 27 H 42 O 4
10
C 32 H 60 O 6
16-(6-butoxy-3-hydroxy-4,5-
dimethylcyclohex-1-en-1-
yl)-6,10-dihydroxy-
2,6,10,14-tetramethyl
hexadecanoic acid
11
C 28 H 52 O 5
7,9,13-trihydroxyoctacosa-
16,22-dienoic acid
12
C 47 H 81 O 13 P
Phosphatidylinositol (20:4/18:1)
13
C 40 H 68 N 6 O 17 , C 41 H 64 N 10 O 13 ,
C 40 H 64 N 12 O 12
14
C 18 H 36 O 2
iso-1,2-octadecanediol
15
C 7 H 14 O 2
16
C 12 H 22 O 5
3-hydroxyl dodecanedioic acid.
19. The method of claim 18 further comprising calibrating the device prior to a measurement of a serum sample or multiple serum samples;
wherein the calibration is conducted by testing the device on a calibration sample.
20. The method of claim 19 , wherein the calibration sample includes at least three compounds selected from the group consisting of cortisone, lysophatidylinositol (18:1), aspartyl-glutamic acid, 16-(6-butoxy-3-hydroxy-4,5-dimethylcyclohex-1-en-1-yl)-6,10-dihydroxy-2,6,10,14-tetramethyl hexadecanoicacid, ceramide, lysophosphatidylethanolamine (22:6), 2-hydroxyl nonanoic acid, iso-1,2-octadecanediol, 3-hydroxyl dodecanedioic acid, phosphatidylinositol (20:4/18:1), and 7,9,13-trihydroxyoctacosa-16,22-dienoic acid.
21. The method of claim 18 , wherein the concentration of metabolites 1 through 8 increase by a log base 2 value of at least about 0.2 over the control serum sample; and
wherein the concentration of metabolites 10 through 16 decrease by a log base 2 value of at least about 0.15 versus the control serum sample.