Methods for Diagnosing Prostate Cancer Using MicroRNA Signatures
The present invention provides novel methods and compositions for the diagnosis and treatment of solid cancers. The invention also provides methods of identifying inhibitors of tumorigenesis.
1 .- 33 . (canceled)
34 . A method of diagnosing whether a subject has, or is at risk for developing, prostate cancer, comprising:
a.) comparing the level of at least let-7d gene product and at least one additional miR gene product in a test sample from a subject to a control level of at least one corresponding let-7d gene product and at least one additional miR gene product; and
b.) diagnosing whether the subject has, or is at risk for developing, prostate cancer, if the level of the at least one let-7d gene product and at least one additional miR gene product in the test sample from the subject is greater than a control level of the let-7d gene product and at least one corresponding additional miR gene product.
35 . A method of claim 34 , wherein the at least one additional miR gene product is miR-21.
36 . A method of claim 34 , wherein the at least one additional miR gene product is miR-128a prec.
37 . A method of claim 34 , wherein the at least one additional miR gene product is miR-195.
38 . A method of claim 34 , wherein the at least one additional miR gene product is miR-203.
39 . A method of claim 34 , wherein the at least one additional miR gene product is let-7a-2.
40 . A method of claim 34 , which further comprises: comparing the level of at least one additional miR gene product in a test sample from the subject to a control level of the miR gene product, wherein the at least one additional miR gene product is selected from the group consisting of: let-7d; miR-128a prec; miR-195; miR-203; let-7a-2 prec; miR-34a; miR-20a; miR-218-2; miR-29a; miR-25; miR-95; miR-197; miR-135-2; miR-187; miR-196-1; miR-148; miR-191; miR-21; let-71; miR-198; miR-199a-2; miR-30c; miR-17-5p; miR-92-2; miR-146; miR-181b-1 prec; miR-32; miR-206; miR-184 prec; miR-29a prec; miR-29b-2; miR-149; miR-181b-1; miR-196-1; miR-93-1; miR-223; miR-16-1; miR-101-1 prec; miR-124a-1; miR-26a-1; miR-214; miR-27a; miR-24-1; miR-106a; and miR-199a-1.
41 . A method of claim 34 , which further comprises: comparing the level of at least one additional miR gene product in a test sample from the subject to a control level of the miR gene product, wherein the at least one additional miR gene product is selected from the group consisting of: miR-21; miR-17-5p; miR-191; miR-29b-2; miR-223; miR-128b; miR-199a-1; miR-24-1; miR-24-2; miR-146; miR-155; miR-181b-1; miR-20a; miR-107; miR-32; miR-92-2; miR-214; miR-30c; miR-25; miR-221; and miR-106a.
42 . A method of diagnosing whether a subject has, or is at risk for developing, prostate cancer, comprising:
a.) comparing the level of at least miR-128a prec gene product and at least one additional miR gene product in a test sample from a subject to a control level of at least one corresponding miR-128a prec gene product and at least one additional miR gene product; and
b.) diagnosing whether the subject has, or is at risk for developing, prostate cancer, if the level of the at least one miR-128a prec gene product and at least one additional miR gene product in the test sample from the subject is greater than a control level of the miR-128a prec gene product and at least one corresponding additional miR gene product.
43 . A method of claim 42 , wherein the at least one additional miR gene product is miR-21.
44 . A method of claim 42 , wherein the at least one additional miR gene product is miR-195.
45 . A method of claim 42 , wherein the at least one additional miR gene product is miR-203.
46 . A method of claim 42 , wherein the at least one additional miR gene product is let-7a prec.
47 . A method of claim 42 , which further comprises: comparing the level of at least one additional miR gene product in a test sample from the subject to a control level of the miR gene product, wherein the at least one additional miR gene product is selected from the group consisting of: let-7d; miR-128a prec; miR-195; miR-203; let-7a-2 prec; miR-34a; miR-20a; miR-218-2; miR-29a; miR-25; miR-95; miR-197; miR-135-2; miR-187; miR-196-1; miR-148; miR-191; miR-21; let-71; miR-198; miR-199a-2; miR-30c; miR-17-5p; miR-92-2; miR-146; miR-181b-1 prec; miR-32; miR-206; miR-184 prec; miR-29a prec; miR-29b-2; miR-149; miR-181b-1; miR-196-1; miR-93-1; miR-223; miR-16-1; miR-101-1 prec; miR-124a-1; miR-26a-1; miR-214; miR-27a; miR-24-1; miR-106a; and miR-199a-1.
48 . A method of claim 42 , which further comprises: comparing the level of at least one additional miR gene product in a test sample from the subject to a control level of the miR gene product, wherein the at least one additional miR gene product is selected from the group consisting of: miR-21; miR-17-5p; miR-191; miR-29b-2; miR-223; miR-128b; miR-199a-1; miR-24-1; miR-24-2; miR-146; miR-155; miR-181b-1; miR-20a; miR-107; miR-32; miR-92-2; miR-214; miR-30c; miR-25; miR-221; and miR-106a.
49 . A method of diagnosing whether a subject has, or is at risk for developing, prostate cancer, comprising:
a.) comparing the level of at least miR-195 gene product and at least one additional miR gene product in a test sample from a subject to a control level of at least one corresponding miR-195 gene product and at least one additional miR gene product; and
b.) diagnosing whether the subject has, or is at risk for developing, prostate cancer, if the level of the at least one miR-195 gene product and at least one additional miR gene product in the test sample from the subject is greater than a control level of the miR-195 gene product and at least one corresponding additional miR gene product.
50 . A method of claim 49 , wherein the at least one additional miR gene product is miR-21.
51 . A method of claim 49 , wherein the at least one additional miR gene product is miR-203.
52 . A method of claim 49 , wherein the at least one additional miR gene product is let-7a-prec.
53 . A method of claim 49 , which further comprises: comparing the level of at least one additional miR gene product in a test sample from the subject to a control level of the miR gene product, wherein the at least one additional miR gene product is selected from the group consisting of: let-7d; miR-128a prec; miR-195; miR-203; let-7a-2 prec; miR-34a; miR-20a; miR-218-2; miR-29a; miR-25; miR-95; miR-197; miR-135-2; miR-187; miR-196-1; miR-148; miR-191; miR-21; let-71; miR-198; miR-199a-2; miR-30c; miR-17-5p; miR-92-2; miR-146; miR-181b-1 prec; miR-32; miR-206; miR-184 prec; miR-29a prec; miR-29b-2; miR-149; miR-181b-1; miR-196-1; miR-93-1; miR-223; miR-16-1; miR-101-1 prec; miR-124a-1; miR-26a-1; miR-214; miR-27a; miR-24-1; miR-106a; and miR-199a-1.
54 . A method of claim 49 , which further comprises: comparing the level of at least one additional miR gene product in a test sample from the subject to a control level of the miR gene product, wherein the at least one additional miR gene product is selected from the group consisting of: miR-21; miR-17-5p; miR-191; miR-29b-2; miR-223; miR-128b; miR-199a-1; miR-24-1; miR-24-2; miR-146; miR-155; miR-181b-1; miR-20a; miR-107; miR-32; miR-92-2; miR-214; miR-30c; miR-25; miR-221; and miR-106a.
55 . A method of diagnosing whether a subject has, or is at risk for developing, prostate cancer, comprising:
a.) comparing the level of at least miR-203 gene product and at least one additional miR gene product in a test sample from a subject to a control level of at least one corresponding miR-203 gene product and at least one additional miR gene product; and
b.) diagnosing whether the subject has, or is at risk for developing, prostate cancer, if the level of the at least one miR-203 gene product and at least one additional miR gene product in the test sample from the subject is greater than a control level of the miR-203 gene product and at least one corresponding additional miR gene product.
56 . A method of claim 55 , wherein the at least one additional miR gene product is miR-21.
57 . A method of claim 55 , wherein the at least one additional miR gene product is let-7a-prec.
58 . A method of claim 55 , which further comprises: comparing the level of at least one additional miR gene product in a test sample from the subject to a control level of the miR gene product, wherein the at least one additional miR gene product is selected from the group consisting of: let-7d; miR-128a prec; miR-195; miR-203; let-7a-2 prec; miR-34a; miR-20a; miR-218-2; miR-29a; miR-25; miR-95; miR-197; miR-135-2; miR-187; miR-196-1; miR-148; miR-191; miR-21; let-71; miR-198; miR-199a-2; miR-30c; miR-17-5p; miR-92-2; miR-146; miR-181b-1 prec; miR-32; miR-206; miR-184 prec; miR-29a prec; miR-29b-2; miR-149; miR-181b-1; miR-196-1; miR-93-1; miR-223; miR-16-1; miR-101-1 prec; miR-124a-1; miR-26a-1; miR-214; miR-27a; miR-24-1; miR-106a; and miR-199a-1.
59 . A method of claim 55 , which further comprises: comparing the level of at least one additional miR gene product in a test sample from the subject to a control level of the miR gene product, wherein the at least one additional miR gene product is selected from the group consisting of: miR-21; miR-17-5p; miR-191; miR-29b-2; miR-223; miR-128b; miR-199a-1; miR-24-1; miR-24-2; miR-146; miR-155; miR-181b-1; miR-20a; miR-107; miR-32; miR-92-2; miR-214; miR-30c; miR-25; miR-221; and miR-106a.
60 . A method of diagnosing whether a subject has, or is at risk for developing, prostate cancer, comprising:
a.) comparing the level of at least let-7a-prec gene product and at least one additional miR gene product in a test sample from a subject to a control level of at least one corresponding let-7a-prec gene product and at least one additional miR gene product; and
b.) diagnosing whether the subject has, or is at risk for developing, prostate cancer, if the level of the at least one let-7a-prec gene product and at least one additional miR gene product in the test sample from the subject is greater than a control level of the let-7a-prec gene product and at least one corresponding additional miR gene product.
61 . A method of claim 60 , wherein the at least one additional miR gene product is miR-21.
62 . A method of claim 60 , which further comprises: comparing the level of at least one additional miR gene product in a test sample from the subject to a control level of the miR gene product, wherein the at least one additional miR gene product is selected from the group consisting of: let-7d; miR-128a prec; miR-195; miR-203; let-7a-2 prec; miR-34a; miR-20a; miR-218-2; miR-29a; miR-25; miR-95; miR-197; miR-135-2; miR-187; miR-196-1; miR-148; miR-191; miR-21; let-71; miR-198; miR-199a-2; miR-30c; miR-17-5p; miR-92-2; miR-146; miR-181b-1 prec; miR-32; miR-206; miR-184 prec; miR-29a prec; miR-29b-2; miR-149; miR-181b-1; miR-196-1; miR-93-1; miR-223; miR-16-1; miR-101-1 prec; miR-124a-1; miR-26a-1; miR-214; miR-27a; miR-24-1; miR-106a; and miR-199a-1.
63 . A method of claim 60 , which further comprises: comparing the level of at least one additional miR gene product in a test sample from the subject to a control level of the miR gene product, wherein the at least one additional miR gene product is selected from the group consisting of: miR-21; miR-17-5p; miR-191; miR-29b-2; miR-223; miR-128b; miR-199a-1; miR-24-1; miR-24-2; miR-146; miR-155; miR-181b-1; miR-20a; miR-107; miR-32; miR-92-2; miR-214; miR-30c; miR-25; miR-221; and miR-106a.
64 . A method of diagnosing whether a subject has, or is at risk for developing, prostate cancer, comprising:
a.) reverse transcribing at least two miR gene products from a test sample from the subject to provide at least two corresponding miR gene product target oligonucleotides;
b.) hybridizing at least two miR target oligodeoxynucleotides to a microarray comprising miRNA-specific probe oligonucleotides that include at least two corresponding miRNA-specific probe oligonucleotides to provide a hybridization profile for the test sample;
c.) comparing the test sample hybridization profile to a control hybridization profile for at least the two miR gene products; and
d.) diagnosing whether the subject has, or is at risk for developing, prostate cancer if the level of at least two gene products in the test sample is greater than the control level of the two gene products, wherein the two miR gene products are gene products of the miRs selected from the group consisting of: let-7d; miR-128a prec; miR-195; miR-203; let-7a-2 prec; miR-34a; miR-20a; miR-218-2; miR-29a; miR-25; miR-95; miR-197; miR-135-2; miR-187; miR-196-1; miR-148; miR-191; miR-21; let-71; miR-198; miR-199a-2; miR-30c; miR-17-5p; miR-92-2; miR-146; miR-181b-1 prec; miR-32; miR-206; miR-184 prec; miR-29a prec; miR-29b-2; miR-149; miR-181b-1; miR-196-1; miR-93-1; miR-223; miR-16-1; miR-101-1 prec; miR-124a-1; miR-26a-1; miR-214; miR-27a; miR-24-1; miR-106a; and miR-199a-1.