Methods for treating colorectal cancer using prognostic genetic markers
This invention relates to prognostic signatures, and compositions and methods for determining the prognosis of cancer in a patient, particularly for colorectal cancer. Specifically, this invention relates to the use of genetic markers for the prediction of the prognosis of cancer, such as colorectal cancer, based on signatures of genetic markers. In various aspects, the invention relates to a method of predicting the likelihood of long-term survival of a cancer patient, a method of determining a treatment regime for a cancer patient, a method of preparing a treatment modality for a cancer patient, among other methods as well as kits and devices for carrying out these methods.
1. A method for treating a patient previously treated for colorectal cancer, consisting of the steps:
(i) obtaining a CRC tumor sample from a patient, isolating mRNA from said CRC tumor sample;
(ii) reverse transcribing said mRNA into cDNA;
(iii) using polymerase chain reaction (PCR) analysis of said cDNA obtained from the CRC tumor sample to determine the amounts of cDNA derived from the genes encoding WD repeat domain 44 (WDR44), rna binding motif, single stranded interacting protein 1, isoform d (RBMS1), Ras-GTPase activating protein SH3 domain-binding protein 2 (SACMIL), sterol o-acyltransferase acyl-coenzyme a: cholesterol acyltransferase 1 (SOAT1), pdz-binding kinase (PBK), ras-gtpase activating protein sh3 domain-binding protein 2 (G3BP2), zinc finger and BTB domain containing 20 (ZBTB20), zinc finger protein 410 (ZNF410), COMM domain containing 2 (COMMD2), proteasome (prosome, macropain) 26s subunit, atpase, 1 (PSMC1), COX10 homolog, cytochrome c oxidase assembly protein, heme A: famesyltransferase (yeast) (COX10), general transcription factor iiic, polypeptide 5 (63kd) (GTF3C5), hyaluronan-mediated motility receptor (rhamm) (HMMR), ubiquitin-conjugating enzyme e21 3 (UBE2L3), gnas complex locus (GNAS), protein phosphatase 2 (formerly 2a), regulatory subunit b (pr 52), alpha isoform (PP2R2A), ribonuclease, rnase a family, 2 (liver, eosinophil-derived neurotoxin) (RNASE2), short coiled-coil protein (SCOC), proteasome (prosome, macropain) 26s subunit, non-atpase, 9 (PSMD9), eukaryotic translation initiation factor 3, subunit 7 (zeta, 66/67kd) (EIF3 S7), ATPase, Ca++ transporting, plasma membrane 4 (ATP2B4), and atp-binding cassette, sub-family c, member 9, isoform sur2a-delta-14 (ABCC9) by contacting said cDNA from said patient with sets of three oligonucleotides, one oligonucleotide of each set comprising a synthetic forward primer having a length of between 17-30 mer and 20-80% G+C content, another oligonucleotide of said set comprising a synthetic reverse primer having a length of 17-30 mer and 20-80% G+C content, and a third oligonucleotide of said set comprising a reporter fluorescent dye and a quencher fluorescent dye-labeled probe, specific for one of the genes;
(iv) calculating the odds ratio for disease recurrence;
(v) if the odds ratio is 8.4 or higher, the patient is treated with a higher or longer dose of chemotherapeutic agent, pursue aggressive or experimental treatments, and
(vi) if the odds ratio is less than 8.4, the patient is treated with surgery alone.
2. The method of claim 1 , wherein the step of determining the amounts of at least one oligonucleotide derived from the genes is carried out using a nucleotide complementary to at least a portion of said cDNA of said gene.