miRNAs as biomarkers for distinguishing benign from malignant thyroid neoplasms
The present invention concerns methods and compositions for identifying a miRNA profile for a particular condition, such as thyroid nodules or thyroid cancer, and using the profile in the diagnosis of a patient for a condition, such as thyroid nodules or thyroid cancer.
1. A method of treating a subject identified with a papillary thyroid carcinoma, the method comprising:
producing labeled nucleotide sequences from a thyroid sample from a subject;
contacting the thyroid sample from the subject with labeled primers specific for a group of microRNAs consisting of miR-375, miR-146b-5p, mir-138-1*, and miR-204; and
reacting the sample with the labeled primers under conditions to amplify the microRNAs using polymerase chain reaction to produce the labeled nucleotide sequences;
measuring expression levels of microRNAs miR-375, miR-146b-5p, mir-138-1*, and miR-204 from the unclassified thyroid sample from the subject with the labeled modified nucleotide microRNA probes that bind specifically to miR-375, miR-146b-5p, mir-138-1*, and miR-204 to produce a microRNA profile based upon the binding of the labeled nucleotide microRNA probes and the labeled nucleotide sequences produced using the polymerase chain reaction;
comparing the expression levels of the microRNAs in the profile from the unclassified thyroid sample from the subject to a normal thyroid reference level for each miRNA;
identifying the unclassified thyroid sample as papillary thyroid carcinoma when the profile expression levels of miR-375, miR-146b-5p are increased as compared to the normal reference level and mir-138-1* and miR-204 are decreased as compared to the normal reference level; and
treating the subject whose sample was identified as papillary thyroid carcinoma, wherein the treating comprises administering radioactive iodine, radiation, or chemotherapy to the subject identified as having papillary thyroid carcinoma or performing a thyroidectomy on the subject identified as having papillary thyroid carcinoma.
2. The method of claim 1 , wherein the sample is a biopsy.
3. The method of claim 2 , wherein the biopsy is surgical resection or a fine needle aspirate.
4. The method of claim 1 , further comprising obtaining a sample from the subject.