Systems and methods for expression-based discrimination of distinct clinical disease states in prostate cancer
A system for expression-based discrimination of distinct clinical disease states in prostate cancer is provided that is based on the identification of sets of gene transcripts, which are characterized in that changes in expression of each gene transcript within a set of gene transcripts can be correlated with recurrent or non-recurrent prostate cancer. The Prostate Cancer Prognostic system provides for sets of “prostate cancer prognostic” target sequences and further provides for combinations of polynucleotide probes and primers derived there from. These combinations of polynucleotide probes can be provided in solution or as an array. The combination of probes and the arrays can be used for diagnosis. The invention further provides further methods of classifying prostate cancer tissue.
1. A method for treating a subject having prostate cancer, comprising:
(a) obtaining an expression level of at least one coding target sequence and obtaining an expression level of at least one non-coding target sequence, wherein the obtained expression level of the non-coding target sequence is distinct from the obtained expression level of the at least one coding target sequence, from a prostate cancer cell in a sample from the subject having prostate cancer; and
(b) determining whether the prostate cancer cell of the subject comprises a recurrent prostate cancer transcript profile utilizing the expression level of the at least one coding target sequence and the expression level of the at least one non-coding target sequence in the sample; and
(c) if the prostate cancer cell of the subject comprises the recurrent prostate cancer transcript profile as determined utilizing the expression level of the at least one coding target sequence and the expression level of the at least one non-coding target sequence in the sample, then administering a prostate cancer treatment selected from the group consisting of adjuvant chemotherapy, systemic radiation therapy, and anti-androgen therapy, or a combination thereof, to the subject, and if the prostate cancer cell of the subject does not comprise a recurrent prostate cancer transcript profile as determined utilizing the expression level of the at least one coding target sequence and the expression level of the at least one non-coding target sequence in the sample, then monitoring the subject without providing the prostate cancer treatment to the subject.
2. The method of claim 1 , wherein the prostate cancer cell of the subject comprises the recurrent prostate cancer transcript profile, and the prostate cancer treatment selected from the group consisting of adjuvant chemotherapy, systemic radiation therapy, and anti-androgen therapy, or a combination thereof, is administered to the subject.
3. The method of claim 1 , wherein the prostate cancer cell of the subject does not comprise the recurrent prostate cancer transcript profile, and the subject is monitored without providing the prostate cancer treatment to the subject.
4. The method of claim 1 , wherein the sample is selected from the group consisting of an aspirate, a needle biopsy, a cytology pellet, a bulk tissue preparation or a section thereof obtained for example by surgery or autopsy, lymph fluid, blood, plasma, serum, tumors, and organs.
5. The method of claim 1 , wherein the sample is a needle-biopsy sample or surgical resection sample that has been fixed in formalin and embedded in paraffin wax.
6. The method of claim 1 , wherein the obtaining the expression level of the at least one coding target sequence and/or the expression level of the at least one non-coding target sequences comprises a method selected from the group consisting of RT-PCR, Northern blotting, ligase chain reaction, array hybridization, and a combination thereof.
7. The method of claim 1 , wherein at the least one coding and the at least one non-coding target sequence is selected from SEQ ID NOs: 1-2114.
8. The method of claim 1 , wherein obtaining the expression level of the at least one coding target sequence and/or the expression level of the at least one non-coding target sequence comprises amplifying the target sequences.
9. The method of claim 1 , wherein obtaining the expression level of the at least one coding target sequence and/or the expression level of the at least one non-coding target sequence comprises sequencing the target sequences.
10. The method of claim 1 , wherein obtaining the expression level of the at least one coding target sequence and/or the expression level of the at least one non-coding target sequence comprises extracting the target sequences from the sample.
11. The method of claim 1 , wherein determining whether the prostate cancer has a recurrent prostate cancer transcript profile based on the expression level of the at least one coding target sequence and the expression level of the at least one non-coding target sequence comprises determining via a computer model or algorithm.
12. The method of claim 11 , wherein the computer model or algorithm is linear.
13. The method of claim 1 , wherein the non-coding target sequence is not part of an RNA molecule that is translated into protein.
14. The method of claim 1 , wherein the non-coding target sequence is not associated with a gene locus.