Diagnosing and monitoring CNS malignancies using MicroRNA
The use of specific microRNAs (miRNAs) present in CSF as biomarkers for particular brain malignancies and disease activity.
1. A method of detecting or making a diagnosis between metastatic and primary brain tumors, the method comprising:
determining, using real time polymerase chain reaction (RT-PCR) or an RNA expression assay, levels of miR-10b, miR-21, and miR-200 in a sample comprising cerebrospinal fluid (CSF) from a subject, and
comparing the levels of miR-10b, miR-21, and miR-200 to reference levels of miR-10b, miR-21, and at least one miR-200 family member, and
determining that the subject does not have a metastatic or primary brain tumor when the levels of all of miR200, miR-10b or miR-21 are below the reference levels;
diagnosing a metastatic or primary brain tumor in a subject who has levels of miR-10b or miR-21 above the reference levels, and administering a treatment for a metastatic or primary brain tumor to the subject; and
diagnosing a metastatic brain tumor when the levels of the miR-200 family member are above the reference level, and administering a treatment for metastatic brain cancer to a subject who has levels of the miR-200 family member above the reference level.
2. The method of claim 1 , wherein the miR-200 family member is selected from the group consisting of miR-200a, miR-200b, and miR-200c.
3. A computer-implemented method of assigning a sample into a category, the method comprising:
determining levels of miR-10b, miR-21, and at least one miR-200 family member, in a sample comprising cerebrospinal fluid (CSF) from a subject, to provide a subject dataset;
downloading the subject dataset into a computer system having a memory, an output device, and a processor programmed for executing an algorithm, wherein the algorithm assigns the datasets into one of two categories using levels of miR-10b, miR-21, and at least one miR-200 family member;
assigning the subject dataset into the first or second category using the programmed processor; and
generating an output comprising a report indicating the assignment to the first or second category.
4. The method of claim 3 , wherein the first category is presence of a primary brain tumor and the second category is presence of a metastatic brain tumor.
5. The method of claim 3 , wherein the first category is presence of a primary brain tumor or a metastatic brain tumor, and the second category is absence of a primary brain tumor or a metastatic brain tumor.
6. The method of claim 3 , wherein the algorithm is a linear algorithm or radial basis function.
7. The method of claim 3 , wherein the algorithm is a linear algorithm comprising: (a*miR-125b)+(b*miR-10b)+(c*miR-21)+(d*miR-141)+(e*miR-200a)+(f*miR-200b)+(g*miR-200c)−h, wherein a-g are weights and h is a constant.
8. The method of claim 3 , wherein the miR-200 family member is selected from the group consisting of miR-200a, miR-200b, miR-200c, miR-141, and miR-429.
9. A method of detecting or making a diagnosis between metastatic and primary brain tumors, the method comprising:
determining, using real time polymerase chain reaction (RT-PCR) or an RNA expression assay, levels of miR-10b, miR-21, and at least one miR-200 family member in a sample comprising cerebrospinal fluid (CSF) from a subject, and
using a suitably programmed processor to apply a linear algorithm to the levels of miR-10b, miR-21, and miR-200 to classify the sample as (i) a primary brain tumor or (ii) a metastatic brain tumor, and
diagnosing a metastatic brain tumor in a subject classified as having a metastatic brain tumor, and diagnosing a primary brain tumor in a subject classified as having a primary brain tumor.
10. The method of claim 9 , comprising:
selecting a subject classified as having a metastatic brain tumor, and administering a treatment for metastatic brain cancer to the subject; or
selecting a subject classified as having a metastatic or primary brain tumor, and
administering a treatment for primary brain cancer to the subject.
11. The method of claim 9 , comprising determining levels of miR-125b, miR-10b, miR-21, miR-141, miR-200a, miR-200b, and miR-200c, wherein the linear algorithm comprises: (a*miR-125b)+(b*miR-10b)+(c*miR-21)+(d*miR-141)+(e*miR-200a)+(f*miR-200b)+(g*miR-200c)−h, wherein a-g are weights and h is a constant.