Prognostic and predictive breast cancer signature
AssigneeThe University of Chicago
InventorsMarsha Rosner, Miao Sun, Unjin Lee
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Abstract
Embodiments of the invention are directed to methods of determining the prognosis of a breast cancer patient by evaluating a specified set of genes. Specifically, methods may comprise calculating a prognosis score based on a particular algorithm. Also disclosed are compositions, kits and methods for treating cancer in a subject in need thereof are disclosed involving one or more upstream activators and/or downstream effectors of TET1.
Claims50
A method for calculating a prognosis score of a breast cancer patient, comprising:
- a) measuring the level of expression or activity in a breast cancer sample of at least four of the following seven biomarkers:
- RKIP, MMP1, OPN, HMGA2, CXCR4, let-7, and BACH1;
- b) comparing the level of expression or activity of each biomarker measured in a) to a reference expression level or activity;
- c) calculating a prognosis score, using a computer algorithm, wherein the prognosis score is based on comparisons in b).
The method of any one of claims 9 to 10, wherein the method further comprises predicting a patient's response to DNMT inhibitor therapy, wherein the patient is predicted to respond to DNMT therapy when the level of expression or activity of RKIP is lower than a reference expression level or activity or wherein the patient is predicted to not benefit from DNMT therapy when the level of expression or activity of RKIP is higher than a reference expression level or activity.
A method for evaluating the response of a breast cancer patient to a breast cancer treatment, comprising:
- a) determining in a breast cancer sample from a patient under or after a breast cancer treatment that the sample has a prognosis score that indicates a poor prognosis, wherein the prognosis score is calculated based on:
- i) the level of expression or activity of at least four of the following seven biomarkers:
- RKIP, MMP1, OPN, HMGA2, CXCR4, let-7, and BACH1;
- or
- ii) the level of expression of at least four of the following 30 genes in the breast cancer sample:
- RKIP, MMP1, OPN, HMGA2, CXCR4, ARID3B, CCNJ, GOLT1B, HIC2, IGF2BP3, IL13, MAP4K4, NF2, PAPPA, SLC6A1, TGFBR1, ZC3H3, BMPER, DYM, FBXO42, FRMPD4, HERC3, HS3ST3B1, IL1RAP, IL7, MAGEC1, MYCT1, PDE1C, PRDM1, and RCAN3;
- and
- b) identifying the patient as being at high risk of a poor response to the breast cancer treatment.
A method of treating a patient determined to have a breast cancer, comprising:
- a) identifying the patient as having a prognosis score that indicates a poor prognosis, wherein the prognosis score is calculated based on:
- i) the level of expression or activity of at least four of the following seven biomarkers:
- RKIP, MMP1, OPN, HMGA2, CXCR4, let-7, and BACH1;
- or
- ii) the level of expression of at least four of the following 30 genes in the breast cancer sample:
- RKIP, MMP1, OPN, HMGA2, CXCR4, ARID3B, CCNJ, GOLT1B, HIC2, IGF2BP3, IL13, MAP4K4, NF2, PAPPA, SLC6A1, TGFBR1, ZC3H3, BMPER, DYM, FBXO42, FRMPD4, HERC3, HS3ST3B1, IL1RAP, IL7, MAGEC1, MYCT1, PDE1C, PRDM1, and RCAN3;
- and
- b) administering a treatment that inhibits or reduces the expression level of the RKIP gene and/or increases or enhances the expression level of one or more of genes:
- MMP1, OPN, HMGA2, CXCR4, ARID3B, CCNJ, GOLT1B, HIC2, IGF2BP3, IL13, MAP4K4, NF2, PAPPA, SLC6A1, TGFBR1, ZC3H3, BMPER, DYM, FBXO42, FRMPD4, HERC3, HS3ST3B1, IL1RAP, IL7, MAGEC1, MYCT1, PDE1C, PRDM1, and RCAN3.
A method of treating a patient determined to have a breast cancer, comprising:
- a) identifying the patient as having a prognosis score that indicates a favorable prognosis, wherein the prognosis score is calculated based on:
- i) the level of expression or activity of at least four of the following seven biomarkers:
- RKIP, MMP1, OPN, HMGA2, CXCR4, let-7, and BACH1;
- or
- ii) the level of expression of at least four of the following 30 genes in the breast cancer sample:
- RKIP, MMP1, OPN, HMGA2, CXCR4, ARID3B, CCNJ, GOLT1B, HIC2, IGF2BP3, IL13, MAP4K4, NF2, PAPPA, SLC6A1, TGFBR1, ZC3H3, BMPER, DYM, FBXO42, FRMPD4, HERC3, HS3ST3B1, IL1RAP, IL7, MAGEC1, MYCT1, PDE1C, PRDM1, and RCAN3;
- and;
- and
- b) administering a treatment comprising an anthracyclines, taxanes, beta-blockers, ixabepilone, bevacizumab, eribulin, or platinum-based therapy alone or combined with surgery.
A method of treating a patient determined to have a breast cancer, comprising:
- a) measuring the level of expression or activity in a breast cancer sample of RKIP;
- b) comparing the level of expression or activity of RKIP to a reference expression level or activity;
- c) treating the patient with a DNMT inhibitor when the expression level or activity of RKIP is lower than the reference expression level or activity.
- d) treating the patient with a therapy that does not comprise a DNMT inhibitor when the expression level or activity of RKIP is higher than the reference expression level or activity.
A tangible, computer-readable medium comprising computer-readable code that, when executed by a computer, causes the computer to perform operations comprising:
- a) receiving information corresponding to:
- i) the level of expression or activity of at least four of the following seven biomarkers:
- RKIP, MMP1, OPN, HMGA2, CXCR4, let-7, and BACH1;
- or ii) the level of expression of at least four of the following 30 genes in the breast cancer sample:
- RKIP, MMP1, OPN, HMGA2, CXCR4, ARID3B, CCNJ, GOLT1B, HIC2, IGF2BP3, IL13, MAP4K4, NF2, PAPPA, SLC6A1, TGFBR1, ZC3H3, BMPER, DYM, FBXO42, FRMPD4, HERC3, HS3ST3B1, IL1RAP, IL7, MAGEC1, MYCT1, PDE1C, PRDM1, and RCAN3 in a breast cancer sample from a patient;
- and
- b) calculating a prognosis score, using a computer algorithm, based on the level of expression or activity of each biomarker gene received in a) as compared to a reference expression level or activity.
A method of diagnosing a subject, the method comprises:
- analyzing a biological sample from the subject for expression of HMGA2, TET1, HOXA7, and HOXA9;
- comparing expression levels of the HMGA2, TET1, HOXA7, and HOXA9 in the biological sample to a respective expression reference level of HMGA2, TET1, HOXA7, and HOXA9 in a control sample;
- and
- diagnosing the subject with at least one of a decreased survival rate, a poor prognosis, a faster progression of a cancer, and a higher risk of relapse of a cancer, when the expression level of HMGA2 in the biological sample is higher than that of the respective control sample and the expression levels of TET1, HOXA7, and HOXA9 in the biological sample are lower than the respective expression reference level of the control sample.
Dependencies are inferred from the claim text.