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 chemokine (C-X-C motif) ligand 10 (CXCL10), TNF receptor superfamily, member 6 (FAS), chemokine (C-X-C motif) ligand 9 (CXCL9), tousled-like kinase 1 (TLK1), chemokine (C-X-C motif) ligand 11 (CXCL11), T-LAK cell-originated protein kinase (PBK), phosphoserine aminotransferase 1 (PSAT1), MAD2 mitotic arrest deficient-like 1 (yeast) (MAD2L1), carbonic anhydrase II (CA2), granzyme B (granzyme 2, cytotoxic T-lymphocyte-associated serine esterase 1) (GZMB), solute carrier family 4, sodium bicarbonate cotransporter, member 4 (SLC4A4), discs, large homolog 7 (Drosophila) (DLG7), tumor necrosis factor receptor superfamily, member 11a, activator of NFKB (TNFRSF11A), KIT ligand (KITLG), indoleamine-pyrrole 2,3 dioxygenase (INDO), guanylate binding protein 1, interferon-inducible, 67 kDa (GBP1), chemokine (C-X-C motif) ligand 13 (B-cell chemoattractant) (CXCL13), chloride channel, calcium activated, family member 4 (CLCA4), and Purkinje cell protein 4 (PCP4) 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 24.1 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 24.1, 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.