MicroRNA Expression Abnormalities in Pancreatic Endocrine and Acinar Tumors

Abstract

The present invention provides novel methods and compositions for the diagnosis, prognosis and treatment of pancreatic cancer. The invention also provides methods of identifying anti-pancreatic cancer agent.

What is claimed is: 
     
         1 . A method of determining whether a subject having a pancreatic cancer has, or is at risk for developing, a liver metastasis, the method comprising:
 extracting from the subject a test sample comprising a miR-21 gene product;   measuring the level of the gene product in the test sample;   determining whether the subject has, or is at risk for developing, pancreatic cancer by comparing the level of the gene product in the test sample to the level of a corresponding miR gene product in a control sample; and,   correlating an increase in the level of the miR-103 gene product in the test sample, relative to the level of the corresponding miR gene product in the control sample, as being indicative of a diagnosis of the subject either having, or being at risk for developing, a liver metastasis.   
     
     
         2 . The method according to  claim 1 , wherein the measuring the level of the miR-21 gene product in the test sample is carried out by analyzing the test sample with a RT-PCR, a microarray and/or a Northern blot electrophoretic device. 
     
     
         3 . The method according to  claim 1 , further comprising: confirming diagnosis by searching, or periodically monitoring, for symptoms which are associated with pancreatic cancer and exhibited by the subject when there is an increase in the level of the miR-21 gene product in the test sample, relative to the level of the corresponding miR gene product in the control sample. 
     
     
         4 . The method according to  claim 1 , wherein the pancreatic cancer is a pancreatic endocrine tumor (PET). 
     
     
         5 . The method according to  claim 4 , wherein the pancreatic cancer is at least one pancreatic endocrine tumor (PET) selected from the group consisting of gastrinoma, insulinoma, somatostatinoma, VIPoma, and glucagonoma. 
     
     
         6 . The method according to  claim 1 , further comprising: confirming diagnosis by searching, or periodically monitoring, for symptoms of hormone hypersecretion associated with PET and exhibited by the subject when there is an increase in the level of the miR-21 gene product in the test sample, relative to the level of the corresponding miR gene product in the control sample. 
     
     
         7 . The method according to  claim 6 , wherein the hormone is at least one hypersecreted hormone selected from the group consisting of gastrin, insulin, somatostatin, vasoactive intestinal polypeptide (VIP), and glucagon. 
     
     
         8 . The method according to  claim 1 , further comprising: communicating to the subject the diagnosis of having, or being at risk for developing, liver metastasis of pancreatic cancer when there is an increase in the level of the miR-21 gene product in the test sample, relative to the level of the corresponding miR gene product in the control sample. 
     
     
         9 . A method of determining whether a subject having a pancreatic cancer has, or is at risk for developing, a liver metastasis, the method comprising:
 isolating RNA from a test sample extracted from the subject;   reverse transcribing the RNA isolated from the test sample to provide at least one target oligodeoxynucleotide;   hybridizing the at least one target oligodeoxynucleotide to a microarray comprising at least one miR-21 miRNA-specific probe oligonucleotide to provide a hybridization profile for the test sample;   determining whether the subject has, or is at risk for developing, a liver metastasis of pancreatic cancer by comparing the signal of the miR-21 miRNA in the hybridization profile for the test sample to the signal of a corresponding miRNA in the hybridization profile for a control sample; and,   correlating a up-regulated signal of the miR-103 miRNA in the test sample, relative to the signal of the corresponding miRNA in the control sample, as being indicative of a diagnosis of the subject either having, or being at risk for developing, a liver metastasis of pancreatic cancer.   
     
     
         10 . The method according to  claim 9 , further comprising: confirming diagnosis by searching, or periodically monitoring, for symptoms which are associated with pancreatic cancer and exhibited by the subject when there is an upregulated signal of the miR-21 miRNA in the test sample, relative to the signal of the corresponding miRNA in the control sample. 
     
     
         11 . The method according to  claim 9 , wherein the pancreatic cancer is a pancreatic endocrine tumor (PET). 
     
     
         12 . The method according to  claim 9 , wherein the pancreatic cancer is at least one pancreatic endocrine tumor (PET) selected from the group consisting of gastrinoma, insulinoma, somatostatinoma, VIPoma, and glucagonoma. 
     
     
         13 . The method according to  claim 12 , further comprising: confirming diagnosis by searching, or periodically monitoring, for symptoms of hormone hypersecretion associated with PET and exhibited by the subject when there is an upregulated signal of the miR-21 miRNA in the test sample, relative to the signal of the corresponding miRNA in the control sample. 
     
     
         14 . The method according to  claim 13 , wherein the hormone is at least one hypersecreted hormone selected from the group consisting of gastrin, insulin, somatostatin, vasoactive intestinal polypeptide (VIP), and glucagon.