Biological patterns for diagnosis and treatment of cancer
The present invention provides methods for diagnosing cancers, such as prostate cancer. Also, methods for evaluating the prostate cancer state of a patient are described herein. These methods involve the detection, analysis, and classification of biological patterns in biological samples. The biological patterns are obtained using, for example, mass spectrometry systems, antibody based techniques, or nucleic acid based techniques. The present invention also includes therapeutic and prophylactic agents that target the biomarkers described herein. Also, the present invention provides methods for the treatment of prostate cancer using the markers described herein or agents that mimic the properties of these markers.
1 . A method of analyzing a prostate cancer state of a patient comprising:
identifying a first subset of prostate cancer markers in a biological sample, wherein said markers in said first subset comprise at least one marker from a first set of prostate cancer markers, said markers in said first set being that marker that can provide mass spectral signals selected from following approximate m/z values:
Biomarker
(*molecular weight
for the indicated
entity is as shown or
Observed m/z
+1 dalton)
(thomson)
1*
2.9511E+02
2
1.5433E+03
1.3890E+03
1.2629E+03
1.1577E+03
1.0687E+03
9.9246E+02
9.2636E+02
8.6852E+02
8.1749E+02
7.7213E+02
7.3155E+02
6.9502E+02
6.6197E+02
and
providing information regarding a prostate cancer state, wherein said information is based on a review of said first subset of prostate cancer markers.
2 . The method of claim 1 wherein said markers in said first set are further characterized by following molecular weights and charge states:
Biomarker
(*molecular weight
for the indicated
monoisotopic
entities is as
Molecular
shown or +1
Observed m/z
Weight
dalton)
Charge
(thomson)
(Daltons)
1*
1
2.9511E+02
294
2
9
1.5433E+03
13880
10
1.3890E+03
13880
11
1.2629E+03
13880
12
1.1577E+03
13880
13
1.0687E+03
13880
14
9.9246E+02
13880
15
9.2636E+02
13880
16
8.6852E+02
13880
17
8.1749E+02
13880
18
7.7213E+02
13880
19
7.3155E+02
13880
20
6.9502E+02
13880
21
6.6197E+02
13880
3 . The method of claim 2 further comprising:
identifying a second subset of prostate cancer markers in a biological sample from a second set of prostate cancer markers, said second set comprising at least one marker selected from prostate specific antigen, human glandular kallikrein 2, prostatic acid phosphatase, prostate-specific membrane antigen, androgen receptor, insulin-like growth factor, and insulin-like growth factor binding protein.
4 . The method of claim 1 wherein said markers are identified using a mass spectrometry system.
5 . The method of claim 4 wherein said mass spectrometry system is a time-of-flight mass spectrometry system.
6 . The method of claim 4 wherein said biological sample is separated using microchannel electrophoresis or capillary electrophoresis on a chip format.
7 . The method of claim 4 wherein said biological sample is prepared and/or separated on a microfluidics device.
8 . The method of claim 4 wherein said biological sample is delivered to said mass spectrometry system by electrospray ionization.
9 . The method of claim 4 wherein said biological sample is delivered to said mass spectrometry system by matrix assisted laser desorption ionization.
10 . The method of claim 1 wherein said markers are identified using at least one technique selected from an antibody-based technique, a multiplexed antibody array, a multiplexed antibody bead, a protein affinity chip, an aptamer, and a microsequencing technique.
11 . A diagnostic product for prostate cancer comprising at least one component adapted and configured for performing the method as recited in claim 1 .
12 . A method of analyzing a prostate cancer state of a patient comprising:
reviewing a pattern of prostate cancer markers from a patient, said pattern comprising at least one marker from a set of markers that can provide mass spectral signals selected from following approximate m/z values:
Biomarker
(*molecular weight
for the indicated
entity is as shown or
Observed m/z
+1 dalton)
(thomson)
1*
2.9511E+02
2
1.5433E+03
1.3890E+03
1.2629E+03
1.1577E+03
1.0687E+03
9.9246E+02
9.2636E+02
8.6852E+02
8.1749E+02
7.7213E+02
7.3155E+02
6.9502E+02
6.6197E+02
and providing an information regarding a prostate cancer state to said patient, a health care provider or a health care manager, said information being based on said review of pattern.
13 . The method of claim 12 wherein said markers in said set are further characterized by following approximate molecular weights and charge states:
Biomarker
(*molecular
weight for the
indicated
monoisotopic
entities is as
Molecular
shown or +1
Observed m/z
Weight
dalton)
Charge
(thomson)
(Daltons)
1*
1
2.9511E+02
294
2
9
1.5433E+03
13880
10
1.3890E+03
13880
11
1.2629E+03
13880
12
1.1577E+03
13880
13
1.0687E+03
13880
14
9.9246E+02
13880
15
9.2636E+02
13880
16
8.6852E+02
13880
17
8.1749E+02
13880
18
7.7213E+02
13880
19
7.3155E+02
13880
20
6.9502E+02
13880
21
6.6197E+02
13880
14 . An computer-readable medium comprising:
a medium suitable for transmission of a result of an analysis of a biological sample; said medium comprising an information regarding a prostate cancer state of a subject, wherein said information is derived using the method of claim 1 or 12 .
15 . A method of analyzing a prostate cancer state of a patient comprising:
identifying a subset of prostate cancer markers in a biological sample, wherein said markers in said subset comprise at least one marker from a set of prostate cancer markers, said markers in said set being characterized by following molecular weights:
Biomarker
(*molecular
weight for the
indicated entities
is as shown
Molecular Weight
or +1 dalton)
(Daltons)
1*
294
2
13880
3
1050
4
519
5
9061
6
4201
7*
496
8
3331
9
2162
10
6169
11
3307
12
9288
13
7728
14
9289
15
3224
16
764
17*
618
18
5720
19
1397
20
11439
21
14043
22
1626
23*
333
24
13727
25
13876
26*
228
27*
326
28
965
29*
256
30
624
31
894
32
856
33
12451
34
1855
35
11729
36
13897
37
13841
38
13978
39
6630
40*
686
41*
312
42
1465
43
981
44
943
45*
272
46*
228
47*
341
and providing information regarding a prostate cancer state, said information being based on a review of said subset of prostate cancer markers.
16 . The method of claim 15 wherein said markers in said first subset are further characterized by following charge states and/or m/z ratios:
Biomarker
(*molecular weight
for the indicated
Molecular
monoisotopic entities is
Observed m/z
Weight
as shown or +1 dalton)
Charge
(thomson)
(Daltons)
3
2
5.2576E+02
1050
4
1
5.2035E+02
519
2
2.6067E+02
519
5
8
1.1336E+03
9061
9
1.0077E+03
9061
10
9.0707E+02
9061
6
4
1.0513E+03
4201
5
8.4127E+02
4201
7*
1
4.9723E+02
496
8
3
1.1113E+03
3331
4
8.3369E+02
3331
5
6.6715E+02
3331
9
3
7.2164E+02
2162
4
5.4148E+02
2162
10
6
1.0291E+03
6169
7
8.8222E+02
6169
8
7.7207E+02
6169
11
4
8.2773E+02
3307
12
7
1.3279E+03
9288
8
1.1620E+03
9288
9
1.0330E+03
9288
10
9.2982E+02
9288
13
7
1.1050E+03
7728
8
9.6701E+02
7728
9
8.5967E+02
7728
14
7
1.3279E+03
9289
8
1.1621E+03
9289
9
1.0331E+03
9289
10
9.2986E+02
9289
15
4
8.0696E+02
3224
5
6.4576E+02
3224
16
1
7.6536E+02
764
2
3.8318E+02
764
17*
1
6.1935E+02
618
18
6
9.5430E+02
5720
7
8.1812E+02
5720
8
7.1598E+02
5720
9
6.3653E+02
5720
19
2
6.9929E+02
1397
20
12
9.5422E+02
11439
13
8.8089E+02
11439
14
8.1804E+02
11439
15
7.6357E+02
11439
16
7.1591E+02
11439
17
6.7386E+02
11439
18
6.3648E+02
11439
21
13
1.0812E+03
14043
14
1.0040E+03
14043
15
9.3718E+02
14043
16
8.7867E+02
14043
17
8.2704E+02
14043
18
7.8115E+02
14043
19
7.4009E+02
14043
22
3
5.4295E+02
1626
4
4.0747E+02
1626
23*
1
3.3413E+02
333
24
13
1.0569E+03
13727
14
9.8152E+02
13727
15
9.1615E+02
13727
16
8.5896E+02
13727
17
8.0849E+02
13727
18
7.6363E+02
13727
19
7.2349E+02
13727
25
14
9.9214E+02
13876
15
9.2607E+02
13876
16
8.6825E+02
13876
17
8.1723E+02
13876
18
7.7189E+02
13876
26*
1
2.2911E+02
228
27*
1
3.2712E+02
326
28
2
4.8368E+02
965
29*
1
2.5715E+02
256
30
1
6.2533E+02
624
2
3.1316E+02
624
3
2.0911E+02
624
31
2
4.4813E+02
894
32
1
8.5739E+02
856
2
4.2920E+02
856
33
7
1.7797E+03
12451
8
1.5574E+03
12451
9
1.3845E+03
12451
34
3
6.1932E+02
1855
35
10
1.1739E+03
11729
11
1.0673E+03
11729
12
9.7840E+02
11729
13
9.0322E+02
11729
14
8.3878E+02
11729
36
13
1.0700E+03
13897
14
9.9366E+02
13897
15
9.2748E+02
13897
16
8.6957E+02
13897
17
8.1848E+02
13897
18
7.7307E+02
13897
19
7.3243E+02
13897
20
6.9586E+02
13897
37
11
1.2593E+03
13841
12
1.1544E+03
13841
13
1.0657E+03
13841
14
9.8967E+02
13841
15
9.2376E+02
13841
16
8.6609E+02
13841
17
8.1520E+02
13841
18
7.6997E+02
13841
19
7.2949E+02
13841
38
11
1.2717E+03
13978
12
1.1659E+03
13978
13
1.0762E+03
13978
14
9.9944E+02
13978
15
9.3288E+02
13978
16
8.7464E+02
13978
17
8.2325E+02
13978
18
7.7757E+02
13978
39
6
1.1060E+02
6630
7
9.4818E+02
6630
8
8.2978E+02
6630
9
7.3769E+02
6630
10
6.6402E+02
6630
11
6.0375E+02
6630
40*
1
6.8650E+02
686
41*
1
3.1314E+02
312
42
2
7.3335E+02
1465
3
4.8924E+02
1465
4
3.6718E+02
1465
43
2
4.9167E+02
981
44
1
9.4442E+02
943
2
4.7271E+02
943
45*
1
2.7310E+02
272
46*
1
2.2911E+02
228
47*
1
3.4215E+02
341
17 . A method of analyzing prostate cancer states comprising identifying the presence of transthyretin, fragments of transthyretin, and/or post-translationally modified forms of transthyretin in a biological sample and making a decision regarding a prostate cancer state, wherein said biological sample is obtained from a subject with serum PSA levels of less than about 6 ng/ml.
18 . A method of analyzing a prostate cancer state of a patient comprising:
identifying a subset of prostate cancer markers in a biological sample, wherein said markers said subset comprise at least one marker from a set of prostate cancer markers, said markers said set being identified with mass spectroscopy and said markers in said set being characterized by following molecular weights:
Biomarker
(*molecular
weight for the
indicated entities
Molecular Weight
is as shown or +1 dalton)
(Daltons)
1*
294
2
13880
3
1050
4
519
5
9061
6
4201
7*
496
8
3331
9
2162
10
6169
11
3307
12
9288
13
7728
14
9289
15
3224
16
764
17*
618
18
5720
19
1397
20
11439
21
14043
22
1626
23*
333
24
13727
25
13876
26*
228
27*
326
28
965
29*
256
30
624
31
894
32
856
33
12451
34
1855
35
11729
36
13897
37
13841
38
13978
39
6630
40*
686
41*
312
42
1465
43
981
44
943
45*
272
46*
228
47*
341
and providing information regarding a prostate cancer state, said information being based on a review of said subset of prostate cancer markers.