Methods and compositions involving microRNA
The present invention concerns methods and compositions for isolating, enriching, and/or labeling miRNA molecules and for preparing and using arrays or other detection techniques for miRNA analysis. Moreover, the present invention concerns methods and compositions for generating miRNA profiles and employing such profiles for therapeutic, diagnostic, and prognostic applications.
1. A method for identifying a human patient suspected of having cancer as having a marker correlated with cancer based on an increase in miR-21 expression comprising:
a) analyzing miR-21 expression in a biological sample from the patient comprising cells suspected of being cancerous; and,
b) identifying the patient as i) having a marker correlated with cancer if an increase in miR-21 expression compared to a noncancerous biological sample is detected in the biological sample or ii) as not having a marker correlated with cancer if the increase fails to be detected, wherein the compared biological samples are derived from the same tissue type.
2. The method of claim 1 , wherein the biological sample from the patient comprises breast tissue and the increase in miR-21 expression is correlated with breast cancer.
3. The method of claim 2 , further comprising analyzing the sample for 1) an increase in miR-200B and/or 2) a decrease in miR-100, miR-126, miR-143, miR-145, and/or miR-205 compared to a noncancerous breast sample.
4. The method of claim 1 , wherein the biological sample from the patient comprises colon tissue and the increase in miR-21 expression is correlated with colon cancer.
5. The method of claim 4 , further comprising analyzing the sample for 1) an increase in miR-31, miR-106A, miR-200B, miR-203, or miR-223 and/or 2) a decrease in miR-125a, mir-130a, miR-133, miR-135A, miR-143, or miR-145 compared to a noncancerous colon sample.
6. The method of claim 1 , wherein the biological sample from the patient comprises prostate tissue and the increase in miR-21 expression is correlated with prostate cancer.
7. The method of claim 6 , further comprising analyzing the sample for 1) an increase in miR-15A, miR-29, or miR-141 and/or 2) a decrease in miR-188, miR-290, or miR-331 compared to a noncancerous prostate sample.
8. The method of claim 1 , wherein the biological sample from the patient comprises thyroid tissue and the increase in miR-21 expression is correlated with thyroid cancer.
9. The method of claim 8 , further comprising analyzing the sample for 1) an increase in miR-15A or miR-200B and/or 2) a decrease in miR-30A-as, miR-31, miR-135A, miR-138, miR-152, miR-199A-as, miR-203, or miR-331 compared to a noncancerous thyroid sample.
10. The method of claim 1 , wherein the biological sample from the patient comprises bladder tissue and the increase in miR-21 expression is correlated with bladder cancer.
11. The method of claim 10 , further comprising analyzing the sample for 1) an increase in miR-9 as, miR-182, or miR-200B and/or 2) a decrease in miR-133, miR-143, or miR-145 compared to a noncancerous bladder sample.
12. A method for identifying a human patient as having a marker correlated with cancer based on an increase in miR-21 expression comprising:
a) obtaining from a patient a breast, colon, lung, thyroid, or bladder tissue sample comprising cells suspected of being cancerous; and,
b) identifying the patient, based on a determination of the tissue sample, as i) having a marker correlated with cancer if there is an increase in miR-21 expression in the tissue sample compared to a noncancerous tissue of the same type as the tissue sample or ii) as not having a marker correlated with cancer if the increase fails to be detected.
13. The method of claim 11 , wherein the tissue sample comprises breast cells.
14. The method of claim 11 , further comprising treating the patient for cancer after the patient is identified as having a marker correlated with cancer.
15. The method of claim 11 , wherein the tissue sample comprises breast cells and the increase in miR-21 expression is correlated with breast cancer.
16. The method of claim 15 , further comprising analyzing the sample for 1) an increase in miR-15a, miR-16, miR-24, miR-25, or miR-200B and/or 2) a decrease in miR-99, miR-100, miR-126, miR-135A, miR-143, miR-145, miR-197, miR-205, miR-211, miR-298 compared to a noncancerous breast sample.
17. The method of claim 11 , wherein the tissue sample comprises colon tissue and the increase in miR-21 expression is correlated with colon cancer.
18. The method of claim 17 , further comprising analyzing the sample for 1) an increase in miR-31, miR-106A, miR-200B, miR-203, or miR-223 and/or 2) a decrease in miR-125a, mir-130a, miR-133, miR-135A, miR-143, or miR-145 compared to a noncancerous colon sample.
19. The method of claim 11 , wherein the tissue sample comprises thyroid tissue and the increase in miR-21 expression is correlated with thyroid cancer.
20. The method of claim 19 , further comprising analyzing the sample for 1) an increase in miR-15A or miR-200B and/or 2) a decrease in miR-30A-as, miR-31, miR-135A, miR-138, miR-152, miR-199A-as, miR-203, or miR-331 compared to a noncancerous thyroid sample.
21. The method of claim 11 , wherein the tissue sample comprises bladder tissue and the increase in miR-21 expression is correlated with bladder cancer.
22. The method of claim 21 , further comprising analyzing the sample for 1) an increase in miR-9 as, miR-182, or miR-200B and/or 2) a decrease in miR-133, miR-143, or miR-145 compared to a noncancerous bladder sample.
23. A method for identifying a patient as having a marker correlated with cancer based on an increase in miR-21 expression comprising:
a) analyzing miR-21 expression in a breast, colon, lung, thyroid, or bladder sample from a patient suspected of having cancer; and,
b) identifying the patient as having a marker correlated with cancer if an increase in miR-21 expression of at least 50% in the patient's biological sample compared to a noncancerous comparable sample is determined; or identifying the patient as not having a marker correlated with cancer if the increase is not determined.
24. The method of claim 23 , further comprising analyzing the sample for a decrease in miR-143 and/or an increase in miR-200b compared to a noncancerous comparable sample.
25. A method for identifying a patient in need of cancer treatment comprising
a) analyzing miR-21 expression in a biological sample from the patient comprising breast cells suspected of being cancerous;
b) detecting an increase in miR-21 expression compared to a noncancerous breast cell sample; and,
c) identifying the patient as having a marker correlated with breast cancer.
26. The method of claim 25 , further comprising analyzing the sample for 1) an increase in miR-200B and/or 2) a decrease in miR-100, miR-126, miR-143, miR-145, and/or miR-205 compared to a noncancerous breast sample.
27. A method for identifying a human patient as having a marker correlated with breast cancer based on an increase in miR-21 expression comprising:
a) obtaining from a patient a breast tissue sample comprising cells suspected of being cancerous; and,
b) identifying the patient, based on a determination of the tissue sample, as i) having a marker correlated with breast cancer if there is an increase in miR-21 expression in the tissue sample compared to a noncancerous tissue of the same type as the tissue sample or ii) as not having a marker correlated with cancer if the increase fails to be detected.
28. The method of claim 12 , wherein the patient has an increase in miR-21 expression and is identifying as having a marker correlated with breast cancer.