Method of classifying and diagnosing cancer
The invention provides various methods for classifying prostate cancers into subtypes. The classification methods may be used to diagnose or prognose prostate cancers. In one embodiment, the subtypes are PCS1, PCS2, or PCS3. In one embodiment, the PCS1 subtype is most likely to progress to metastatic disease or prostate cancer specific mortality when compared to the PCS2 subtype or PCS3 subtype. In one embodiment, the PCS1 subtype is resistant to enzalutamide.
1. A method for classifying prostate cancer into subtypes and treating prostate cancer, comprising:
a) obtaining a sample from a subject who has prostate cancer;
b) measuring gene expression of genes in the sample from the subject, wherein the genes are STMN1, MCM4, CCNB1, CDC6, CDKN3, EZH2, TPX2, FOXM1, KIF11, HMMR, MKI67, KNTC1, RAB3B, SLC4A4, ANK3, GJB1, SLC12A2, CFD, COL6A1, PTGDS, LTBP4, SOCS3, SPEG, GABRP, PENK, SMARCD3, CLIP3, ACTC1, ASPA, COL4A6, CYP4B1, ROR2, SGCA, SLC2A5, PAGE4, ACOX2, and C16orf45;
c) detecting changes in gene expression of the genes relative to reference samples or values;
d) determining the presence of an expression pattern of the genes associated with PCS1 subtype in the sample from the subject based on the detected changes wherein the expression pattern is an increased expression levels in STMN1, MCM4, CCNB1, CDC6, CDKN3, EZH2, TPX2, FOXM1, KIF11, HMMR, MKI67, and KNTC1 genes, and a decreased expression levels in RAB3B, SLC4A4, ANK3, GJB1, SLC12A2, CFD, COL6A1, PTGDS, LTBP4, SOCS3, SPEG, GABRP, PENK, SMARCD3, CLIP3, ACTC1, ASPA, COL4A6, CYP4B1, ROR2, SGCA, SLC2A5, PAGE4, ACOX2, and C16orf45 genes;
e) classifying the prostate cancer in the subject into the PCS1 subtype; and
f) administering to the subject a therapeutically effective amount of one or more DNA damaging agents selected from cisplatin, PARP inhibitors, or combinations thereof, or a therapeutically effective amount of a mitotic inhibitor, or a therapeutically effective amount of doxetaxel or a salt thereof.
2. The method of claim 1 , wherein the sample comprises a tissue sample or blood.
3. The method of claim 1 , wherein the sample comprises prostate tissue or circulating tumor cells.
4. The method of claim 1 , wherein the PCS1 subtype is resistant to enzalutamide.
5. The method of claim 1 , wherein the PCS1 subtype is characterized in that it has an increased probability of progressing to metastatic disease or prostate cancer specific mortality when compared to PCS2 subtype or PCS3 subtype.
6. A method for prognosing and treating prostate cancer in a subject, comprising:
a) obtaining a sample from the subject who has prostate cancer;
b) measuring expression levels of genes in the sample from the subject, wherein the genes are STMN1, MCM4, CCNB1, CDC6, CDKN3, EZH2, TPX2, FOXM1, KIF11, HMMR, MKI67, KNTC1, RAB3B, SLC4A4, ANK3, GJB1, SLC12A2, CFD, COL6A1, PTGDS, LTBP4, SOCS3, SPEG, GABRP, PENK, SMARCD3, CLIP3, ACTC1, ASPA, COL4A6, CYP4B1, ROR2, SGCA, SLC2A5, PAGE4, ACOX2, and C16orf45;
c) detecting changes in the expression levels of the genes in the sample from the subject relative to reference samples or values;
d) determining the presence of PCS1 subtype's expression pattern of the genes in the sample based on the detected changes wherein the PCS1 subtype expression pattern has increased expression levels in STMN1, MCM4, CCNB1, CDC6, CDKN3, EZH2, TPX2, FOXM1, KIF11, HMMR, MKI67, and KNTC1 genes, and decreased expression levels in RAB3B, SLC4A4, ANK3, GJB1, SLC12A2, CFD, COL6A1, PTGDS, LTBP4, SOCS3, SPEG, GABRP, PENK, SMARCD3, CLIP3, ACTC1, ASPA, COL4A6, CYP4B1, ROR2, SGCA, SLC2A5, PAGE4, ACOX2, and C16orf45 genes;
e) prognosing the prostate cancer in the subject as having a poor clinical outcome; and
f) administering to the subject a therapeutically effective amount of one or more DNA damaging agents selected from cisplatin, PARP inhibitors, or combinations thereof, or a therapeutically effective amount of a mitotic inhibitor, or a therapeutically effective amount of doxetaxel or a salt of doxetaxel, or a combination thereof.
7. The method of claim 6 , wherein the poor clinical outcome comprises lower metastasis-free survival, higher risk of metastatic progression, higher rate of prostate cancer specific mortality, lower overall survival, or more aggressive form of prostate cancer, or a combination thereof.
8. The method of claim 1 , wherein the therapeutic agent is one or more DNA damaging agents selected from cisplatin, PARP inhibitors, or combinations thereof.
9. The method of claim 1 , wherein the subtype is PCS1, and the administered therapeutic agent is a mitotic inhibitor.
10. The method of claim 1 , wherein the subtype is PCS1, and the administered therapeutic agent is docetaxel, or salt of docetaxel, or a combination thereof.
11. The method of claim 1 , wherein the one or more genes further comprise TOP2A, CENPF, ESRP1, SHMT2, AR, RAD54L, HN1, CELSR3, TACC3, and CCNA2.
12. The method of claim 11 , wherein the subtype PSC1 and has an increased expression of TOP2A, CENPF, ESRP1, SHMT2, AR, RAD54L, HN1, CELSR3, TACC3, and CCNA2.
13. The method of claim 11 , wherein the sample comprises circulating tumor cells.
14. The method of claim 6 , wherein the therapeutic agent is one or more DNA damaging agents selected from cisplatin, PARP inhibitors, or combinations thereof.
15. The method of claim 6 , wherein the subtype is PCS1, and the administered therapeutic agent is a mitotic inhibitor.
16. The method of claim 6 , wherein the subtype is PCS1, and the administered therapeutic agent is docetaxel, or salt of docetaxel, or a combination thereof.