Subtyping prostate cancer to predict response to hormone therapy
The present invention relates to methods, systems and kits for the diagnosis, prognosis and the determination of progression of cancer in a subject. The invention also provides biomarkers that define subgroups of prostate cancer, clinically useful classifiers for distinguishing prostate cancer subtypes, bioinformatic methods for determining clinically useful classifiers, and methods of use of each of the foregoing. The methods, systems and kits can provide expression-based analysis of biomarkers for purposes of subtyping prostate cancer in a subject. Further disclosed herein, in certain instances, are probe sets for use in subtyping prostate cancer in a subject. Classifiers for subtyping a prostate cancer are provided. Methods of treating cancer based on molecular subtyping are also provided.
1. A method comprising:
a) providing a biological sample from a subject having prostate cancer;
b) extracting nucleic acids from the biological sample;
c) detecting the presence or expression level in the biological sample for targets CDC20, KIF2C, PHGDH, NUF2, CENPF, EXO1, UBE2T, RRM2, MLPH, GPR160, CCNB1, CXXC5, PTTG1, FGFR4, FOXC1, ESR1, ANLN, BLVRA, EGFR, ACTR3B, NAT1, MYC, SFRP1, MELK, BAG1, CEP55, MKI67, TMEM45B, PGR, MDM2, KRT5, FOXA1, ORC6, CDH3, ERBB2, GRB7, CDC6, MAPT, BIRC5, KRT14, KRT17, TYMS, NDC80, SLC39A6, BCL2, CCNE1, MIA, MYBL2, UBE2C, and MMP11;
d) subtyping the prostate cancer in the subject according to a genomic subtyping classifier based on the presence or expression levels of the plurality of targets, wherein said subtyping comprises assigning the prostate cancer to a luminal B subtype; and
e) administering a treatment comprising androgen deprivation therapy to a subject who has the luminal B subtype.
2. A method comprising:
a) selecting a subject with prostate cancer having a luminal B subtype, wherein the subtype is determined according to a genomic subtyping classifier based on the presence or expression levels in a biological sample from the subject of targets CDC20, KIF2C, PHGDH, NUF2, CENPF, EXO1, UBE2T, RRM2, MLPH, GPR160, CCNB1, CXXC5, PTTG1, FGFR4, FOXC1, ESR1, ANLN, BLVRA, EGFR, ACTR3B, NAT1, MYC, SFRP1, MELK, BAG1, CEP55, MKI67, TMEM45B, PGR, MDM2, KRT5, FOXA1, ORC6, CDH3, ERBB2, GRB7, CDC6, MAPT, BIRC5, KRT14, KRT17, TYMS, NDC80, SLC39A6, BCL2, CCNE1, MIA, MYBL2, UBE2C, and MMP11; and
b) treating the subject with a treatment comprising androgen deprivation therapy.
3. The method of claim 2 , wherein the biological sample is a biopsy.
4. The method of claim 2 , wherein the biological sample is a urine sample, a blood sample or a prostate tumor sample.
5. The method of claim 4 , wherein the blood sample is plasma, serum, or whole blood.
6. The method of claim 2 , wherein the subject is a human.
7. The method of claim 2 , wherein the levels of expression are increased or reduced compared to a control.
8. The method of claim 2 , wherein the levels of expression are obtained by a method comprising in situ hybridization, a PCR-based method, an array-based method, an immunohistochemical method, an RNA assay method, or an immunoassay method.
9. The method of claim 8 , wherein the levels of expression are obtained by a method comprising using a reagent selected from the group consisting of a nucleic acid probe, one or more nucleic acid primers, and an antibody.
10. The method of claim 9 , wherein the levels of expression are obtained by a method comprising measuring the level of an RNA transcript.