USE OF MiR-26 FAMILY AS A PREDICTIVE MARKER FOR HEPATOCELLULAR CARCINOMA AND RESPONSIVENESS TO THERAPY

Abstract

Provided is a method of selecting a patient diagnosed with HCC as a candidate for IFN-α therapy, by detecting the level of microRNA-26 expression in a sample obtained from the patient.

What is claimed is: 
     
         1 . A method of selecting a patient diagnosed with HCC as a candidate for IFN-α therapy, comprising detecting the level of miR-26 expression in a HCC tumor sample obtained from the patient, wherein a 1.5-fold or greater decrease in the level of miR-26 expression in the tumor sample relative to a control indicates the patient is a candidate for IFN-α therapy, wherein expression of miR-26 in the tumor sample is decreased at least 2-fold, at least 2.5-fold, at least 3-fold, at least 3.5-fold, or at least 4-fold. 
     
     
         2 . A method of identifying a therapeutic agent for the treatment of HCC, comprising screening candidate agents in vitro to select an agent that increases expression of miR-26 in HCC cells, thereby identifying an agent for the treatment of HCC. 
     
     
         3 . The method of  claim 1 , wherein screening comprises contacting the candidate agents with the HCC cells. 
     
     
         4 . The method of  claim 1 , wherein expression of miR-26 in the HCC cells is increased at least 2-fold relative to untreated cells. 
     
     
         5 . The method of  claim 1 , wherein expression of miR-26 in the HCC cells is increased at least 3-fold relative to untreated cells. 
     
     
         6 . The method of  claim 1 , wherein expression of miR-26 in the HCC cells is increased at least 4-fold relative to untreated cells. 
     
     
         7 . The method of  claim 1 , wherein the candidate agents are cytokines. 
     
     
         8 . The method of  claim 1 , wherein the candidate agents are small molecules. 
     
     
         9 . The method of  claim 1 , wherein the HCC cells are primary cells obtained from a HCC patient. 
     
     
         10 . The method of  claim 1 , wherein the HCC cells are immortalized cells. 
     
     
         11 . A method of treating a patient diagnosed with HCC, comprising:
 i) detecting the level of miR-26 expression in a tumor sample obtained from the patient;   ii) comparing the level of miR-26 expression in the tumor sample to a control; and   iii) selecting a method of treatment for the patient, wherein treatment comprises IFN-α therapy only if the patient has a 1.5-fold or greater decrease in the level of miR-26 expression in the tumor sample relative to the control.   
     
     
         12 . The method of  claim 11 , wherein miR-26 is miR-26a-1, miR-26a-2, miR-26b, or a combination thereof. 
     
     
         13 . The method of  claim 11 , wherein treatment further comprises liver resection. 
     
     
         14 . The method of  claim 11 , wherein IFN-α therapy comprises administration of IFN-α. 
     
     
         15 . The method of  claim 11 , wherein the control is a non-cancerous tissue sample obtained from the patient. 
     
     
         16 . The method of  claim 11 , wherein the control is a liver sample from a healthy subject. 
     
     
         17 . The method of  claim 11 , wherein the control is a standard value. 
     
     
         18 . The method of  claim 11 , wherein expression of miR-26 in the tumor sample is decreased at least 2-fold, at least 2.5-fold, at least 3-fold or at least 4-fold. 
     
     
         19 . A method for the characterization of hepatocellular carcinoma (HCC), wherein at least one feature of HCC is selected from one or more of the group consisting of: presence or absence of HCC; diagnosis of HCC; prognosis of HCC; therapy outcome prediction; therapy outcome monitoring; suitability of HCC to treatment, such as suitability of HCC to chemotherapy treatment and/or radiotherapy treatment; suitability of HCC to hormone treatment; suitability of HCC for removal by invasive surgery; suitability of HCC to combined adjuvant therapy. 
     
     
         20 . A kit for the detection of HCC, the kit comprising at least one detection probe comprising one or more members of the miR-26 family. 
     
     
         21 . The kit for the detection of HCC according to  claim 20 , wherein the kit is in the form or comprises an oligonucleotide array.