Methods and Materials Related to Ovarian Cancer
AssigneeThe Ohio State University
InventorsCarlo M. Croce, Andrea Vecchione
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Abstract
Described herein are methods for diagnosing ovarian cancer. In particular, certain microRNAs are useful to the response to chemotherapy of ovarian cancer patients.
Claims33
A method of diagnosing ovarian cancer that is resistant to chemotherapeutic intervention in a subject, comprising:
- a) identifying miR-484, miR-642 and/or miR-217 expression levels in a sample from the subject, as compared to control expression levels, and
- b) diagnosing chemoresistant ovarian cancer in the subject if the subject has decreased miR-484, miR-642 and/or miR-217 expression levels compared to the control expression levels, or
- c) diagnosing no chemoresistant ovarian cancer in the subject if the subject does not have decreased miR-484, miR-642 and/or miR-217 expression levels compared to the control expression levels.
A method of determining whether a human subject has a poor survival prognosis for an ovarian cancer, comprising:
- a) measuring the expression levels of a miR gene product signature in a sample of ovarian tissue from the human subject, the miR gene product signature consisting of miR gene products:
- miR-484, mir-642 and/or miR-217;
- and
- b) determining the poor survival prognosis of the human subject when a decrease in the expression levels one or more of the miR gene products in the sample, relative to corresponding expression levels of miR gene products in a control sample of cancer-free ovarian tissue, is indicative of the human subject having a poor survival prognosis for ovarian cancer.
The method of claim 12, wherein step (a), comprises:
- 1) reverse transcribing miR-484, miR-642 and/or miR-217 RNA from the sample to provide a set of target oligodeoxynucleotides;
- 2) hybridizing the target oligodeoxynucleotides to a microarray comprising miR-484, miR-642 and/or miR-217 miRNA-specific probe oligonucleotides to provide a hybridization profile for the test sample;
- and
- 3) comparing the profile of step (2) to control.
A method for determining a chemoresistant ovarian cancer is a subject, the method comprising:
- a) detecting a miRNA expression profile of a sample from the subject,
- b) comparing the miRNA profile of the sample to a miRNA expression profile of a control sample comprised of non-cancerous ovarian cells, and
- c) determining chemoresistant ovarian cancer when the miRNA expression profile comprises a statistically significant change in the expression levels of one or more of:
- hsa-miR-484, hsa-miR-642 and/or hsa-miR-217 in the sample.
A method for the assessment of a clinical condition of a patient, comprising the steps:
- a) providing a biological sample from the patient,
- b) determining expression levels a predetermined signature of miRNAs in the sample to obtain a miRNA expression profile, the predetermined signature of miRNAs comprising at least:
- hsa-miR-484, hsa-miR-642 and/or hsa-miR-217,
- c) comparing the expression levels of step (b) with one or more reference miRNA expression profiles characteristic for different diseases including ovarian cancer, and
- d) assessing the clinical condition of the patient based on the comparison of step (c).
A kit for the assessment of a clinical condition of a patient comprising:
- a) one or more biomarkers for determining a predetermined signature of miRNAs in a biological sample from a patient, the predetermined signature of miRNAs comprising at least one of:
- hsa-miR-484, hsa-miR-642 and/or hsa-miR-217, and
- b) a plurality of miRNA reference expression profiles characteristic for different diseases including ovarian cancer.
A kit for diagnosing ovarian cancer in a patient comprising:
- a) a capture reagent comprising one or more detectors specific for at least one ovarian cancer diagnostic biomarker, wherein at least a first ovarian cancer biomarker is a miR-484 biomarker,
- b) a detection reagent, and
- c) instructions for using the kit to diagnose a patient as having ovarian cancer when the expression levels of the miR-484 diagnostic biomarker in a biological sample from the patient is lower than the expression level of the same biomarkers in a control subject without ovarian cancer.
A set of oligo- or polynucleotides for diagnosing ovarian cancer comprising the sequences of a set of miRNAs selected from:
- miR-484, miR-642 and miR-217, and/or the complements thereof.
A method for diagnosing ovarian cancer in a patient comprising:
- a) detecting expression levels of at least one diagnostic biomarker in a biological sample from the patient, wherein at least a first diagnostic biomarker is a miR-484 biomarker, and
- b) diagnosing the patient as having ovarian cancer when the expression level of at least the mir-484 diagnostic biomarker in the patient sample is lower than normal expression levels of the same biomarker derived from a biological sample from a control subject without ovarian cancer.
Dependencies are inferred from the claim text.