MicroRNAs expression signature for determination of tumors origin
The present invention provides a process for classification of specific cancers and tumors origin through the analysis of the expression patterns of specific microRNAs and nucleic acid molecules relating thereto. Classification according to a microRNA expression framework allows optimization of treatment, and determination of specific therapy.
1. A method of distinguishing between a primary gastrointestinal (GI) tumor and a GI metastatic tumor, the method comprising:
(a) providing RNA from a biological sample obtained from a human subject;
(b) determining an expression profile of nucleic acids consisting of SEQ ID NOS: 1 and 4, by contacting the RNA with probes consisting of (i) a first nucleic acid probe, wherein the sequence of the first nucleic acid probe consists of the complement of SEQ ID NO: 1 and a linker of 10-60 nucleotides on the 3′ end of the complement of SEQ ID NO: 1; (ii) a second nucleic acid probe, wherein the sequence of the second nucleic acid probe consists of the complement of SEQ ID NO: 4 and a linker of 10-60 nucleotides at the 3′ end of the complement of SEQ ID NO: 4; and (iii) optionally a control probe; wherein the probes are attached to a solid support;
(c) comparing the expression profile from the biological sample to a reference expression profile; and
(d) distinguishing the biological sample as a primary GI tumor or a GI metastatic tumor based on the comparison of the expression profiles.
2. The method of claim 1 , wherein an expression level of SEQ ID NO: 4 that is less than or equal to half the expression level of SEQ ID NO: 1 is indicative of a primary GI tumor, and wherein an expression level of SEQ ID NO: 4 that is greater than half the expression level of SEQ ID NO: 1 is indicative of a GI metastatic tumor.
3. The method of claim 1 , wherein the primary GI tumor is selected from the group consisting of colon, pancreas and stomach tumor.
4. The method of claim 1 , wherein the biological sample is selected from the group consisting of bodily fluid, a cell line and a tissue sample.
5. The method of claim 4 , wherein the tissue sample is a fresh, frozen, fixed, wax-embedded or formalin fixed paraffin-embedded (FFPE) tissue.
6. The method of claim 1 , wherein the solid substrate comprises a biochip array.
7. The method of claim 1 , wherein the expression profile is determined by real-time PCR.
8. The method of claim 7 , wherein the real-time PCR further comprises contacting the RNA with a forward primer and a reverse primer.