Microrna assay for detection and management of pancreatic cancer precursors

Abstract

The current invention pertains to miRNAs that are differentially expressed in samples of an individual having pancreatic cancer, or having a high risk of developing pancreatic cancer, as compared to the corresponding sample of an individual not having pancreatic cancer, or having low risk of developing pancreatic cancer, respectively. In certain embodiments, the miRNAs are differentially expressed in a tissue sample or blood plasma sample of an individual having a pancreatic lesion and having a high risk of developing pancreatic cancer as compared to the corresponding tissue sample or blood sample of an individual having the pancreatic lesion and having no risk or low risk of developing pancreatic cancer. These differentially expressed miRNAs can be used as biomarkers for diagnosis, treatment, and/or prevention of pancreatic cancer, particularly, in a subject having a pancreatic lesion. Microarray containing miRNAs indicative of the presence of pancreatic cancer, or having a high risk of pancreatic cancer development, particularly, in a subject having a pancreatic lesion, and methods of use of the microarrays are also provided.

We claim: 
     
         1 . A method of treating and/or preventing the development of pancreatic cancer in a subject, the method comprising:
 (a) detecting the level of expression of one or more miRNAs in a sample from the subject;   (b) comparing the detected expression level to a reference expression level, wherein a differential expression of the one or more miRNAs in the sample, as compared to the reference expression level, is indicative of the presence of pancreatic cancer, or a higher risk of developing pancreatic cancer, versus the absence of pancreatic cancer, or a lower risk of developing pancreatic cancer, respectively; and   (c) administering a therapy to treat and/or prevent the pancreatic cancer to the subject identified as having the pancreatic cancer, or at a higher risk of developing pancreatic cancer.   
     
     
         2 . The method of  claim 1 , wherein a differential expression of the one or more miRNAs in the sample, as compared to the reference expression level, is indicative of a pancreatic cancer precursor (such as intraductal papillary mucinous neoplasm (IPMN)) versus non-IPMN (normal cells). 
     
     
         3 . The method of  claim 1 , wherein the one or more miRNAs are selected from miR-100, miR-99b, miR-99a, miR-342-3p, miR-126, miR-888, miR-130a, let-7c, miR-150, miR-296, miR-199a, miR-199a-3p, and miR-302a. 
     
     
         4 . The method of  claim 1 , wherein the one or more mRNAs are selected from among let-7a-5p, let-7d-5p, let-7f-5p, let-7g-5p, let-7i-5p, miR-107, miR-1260b, miR-126-3p, miR-142-3p, miR-145-5p, miR-146a-5p, miR-148a-3p, miR-15b-5p, miR-181a-5p, miR-191-5p, miR-199a-3p, miR-199b-3p, miR-20a-5p, miR-20b-5p, miR-22-3p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-27a-3p, miR-29c-3p, miR-335-5p, miR-337-5p, miR-340-5p, miR-423-5p, miR-4454, miR-593-3p, and miR-98. 
     
     
         5 . The method of  claim 1 , wherein the one or more mRNAs are selected from among miR-200a-3p, miR-1185-5p, miR-33a-5p, miR-574-3p, and miR-663b. 
     
     
         6 . A method of treating and/or preventing pancreatic cancer in a subject, comprising measuring the level of expression of one or more miRNAs in a sample obtained from the subject; and administering a treatment for the pancreatic cancer, wherein the one or more miRNAs comprise:
 (a) one or more mRNAs selected from among miR-100, miR-99b, miR-99a, miR-342-3p, miR-126, miR-888, miR-130a, let-7c, miR-150, miR-296, miR-199a, miR-199a-3p, and miR-302a; or   (b) one or more mRNAs selected from among let-7a-5p, let-7d-5p, let-7f-5p, let-7g-5p, let-7i-5p, miR-107, miR-1260b, miR-126-3p, miR-142-3p, miR-145-5p, miR-146a-5p, miR-148a-3p, miR-15b-5p, miR-181a-5p, miR-191-5p, miR-199a-3p, miR-199b-3p, miR-20a-5p, miR-20b-5p, miR-22-3p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-27a-3p, miR-29c-3p, miR-335-5p, miR-337-5p, miR-340-5p, miR-423-5p, miR-4454, miR-593-3p, and miR-98; or   (c) one or more mRNAs selected from among miR-200a-3p, miR-1185-5p, miR-33a-5p, miR-574-3p, and miR-663b.   
     
     
         7 . The method of  claim 6 , wherein the one or more miRNAs comprise one or more from among miR-1185-5p, miR-33a-5p, miR-574-3p, and miR-663b. 
     
     
         8 . A composition of matter comprising:
 (a) a microarray chip corresponding to a profile of miRNAs that are differentially expressed in a sample of an individual having pancreatic cancer, or having a high risk of developing pancreatic cancer, as compared to the corresponding sample of an individual having no risk or low risk of developing pancreatic cancer, the microarray chip consisting essentially of oligonucleotides corresponding to one or more of miRNA selected from among miR-100, miR-99b, miR-99a, miR-342-3p, miR-126, miR-888, miR-130a, let-7c, miR-150, miR-296, miR-199a, miR-199a-3p, and miR-302a; or   (b) a microarray chip corresponding to a profile of miRNAs that are differentially expressed in a sample of an individual having a pancreatic lesion and having high risk of developing pancreatic cancer compared to the corresponding sample of an individual having the pancreatic lesion and having no risk or low risk of developing pancreatic cancer, the microarray chip consisting essentially of oligonucleotides corresponding to one or more selected from among miR-100, miR-99b, miR-99a, miR-342-3p, miR-126, miR-888, miR-130a, let-7c, miR-150, miR-296, miR-199a, miR-199a-3p, and miR-302a; or   (c) a microarray chip corresponding to a profile of miRNAs that are differentially expressed in a sample of an individual having a pancreatic cancer precursor (such as intraductal papillary mucinous neoplasm (IPMN)) as compared to a non-IPMN (normal cells), the microarray chip consisting essentially of oligonucleotides corresponding to one or more of miRNA selected from among one or more miRNA selected from among let-7a-5p, let-7d-5p, let-7f-5p, let-7g-5p, let-7i-5p, miR-107, miR-1260b, miR-126-3p, miR-142-3p, miR-145-5p, miR-146a-5p, miR-148a-3p, miR-15b-5p, miR-181a-5p, miR-191-5p, miR-199a-3p, miR-199b-3p, miR-20a-5p, miR-20b-5p, miR-22-3p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-27a-3p, miR-29c-3p, miR-335-5p, miR-337-5p, miR-340-5p, miR-423-5p, miR-4454, miR-593-3p, and miR-98; or   (d) a microarray chip corresponding to a profile of miRNAs that are differentially expressed in a sample of an individual having a malignant intraductal papillary mucinous neoplasm (IPMN)) as compared to a benign IPMN, the microarray chip consisting essentially of oligonucleotides corresponding to one or more of miRNA selected from among one or more miRNA selected from among miR-200a-3p, miR-1185-5p, miR-33a-5p, miR-574-3p, and miR-663b.