In vitro method for identifying pancreatic cancer or intraductal papillary mucinous neoplasm of the pancreas

Inventors

GIRONELLA COS, Meritxel • CASTELLS GARANGOU, ANTONI

Assignees

Hospital Clinic de Barcelona • Centro de Investigacion Biomedica en Red CIBER • Advanced Marker Discovery SL AMADIX

Abstract

The present invention refers to an in vitro method for screening for subjects at risk of developing pancreatic cancer or intraductal papillary mucinous neoplasm of the pancreas (IPMN) comprising: (a) measuring the expression pattern or level of at least hsa-miR-33a*, or of at least hsa-miR-320a, or of at least hsa-let-7e, or of at least hsa-let-7f, or of at least hsa-miR-1257, or of at least hsa-miR-1304, or of at least hsa-miR-151b, or of at least hsa-miR-3120-3p, or of at least hsa-miR-3133, or of at least hsa-miR-3714, or of at least hsa-miR-4468, or of at least hsa-miR-4639-5p, or of at least hsa-miR-4713-5p, or of at least hsa-miR-4714-5p, or of at least hsa-miR-4770, or of at least hsa-miR-548d-3p, or of at least hsa-miR-761, obtained from an isolated biological sample of the subjects to be screened; and (b) comparing said expression pattern or level of at least hsa-miR-33a*, or of at least hsa-miR-320a, or of at least hsa-let-7e, or of at least hsa-let-7f, or of at least hsa-miR-1257, or of at least hsa-miR-1304, or of at least hsa-miR-151b, or of at least hsa-miR-3120-3p, or of at least hsa-miR-3133, or of at least hsa-miR-3714, or of at least hsa-miR-4468, or of at least hsa-miR-4639-5p, or of at least hsa-miR-4713-5p, or of at least hsa-miR-4714-5p, or of at least hsa-miR-4770, or of at least hsa-miR-548d-3p, or of at least hsa-miR-761, of the subjects to be screened with an already established expression pattern or level, wherein over expression of at least any of the above mentioned miRNAs is indicative of pancreatic cancer or intraductal papillary mucinous neoplasm of the pancreas (IPMN).

Core Innovation

The invention relates to an in vitro method for detecting a miRNA biomarker in a test sample from a human subject at risk of developing pancreatic cancer or intraductal papillary mucinous neoplasm of the pancreas (IPMN). The method includes contacting the test sample with a primer specific to a miRNA biomarker comprising hsa-miR-33a*, amplifying the hsa-miR-33a* biomarker to produce an amplification product, and measuring the hsa-miR-33a* expression level by determining the level of the amplification product in the test sample.

The document describes extensive miRNA biomarker lists and highlights discriminatory miRNAs that are validated using next-generation sequencing (NGS) and qRT-PCR across multiple independent cohorts. The validation is reported using both tissue and EUS-FNA samples, with diagnostic performance reported using ROC and AUC metrics.

The described approach is applicable to different sample matrices, including plasma and serum, and is associated with use as kit(s). The invention is grounded in measuring miRNA expression levels in isolated biological samples and comparing the measured expression to reference patterns to support detection of subjects at risk of pancreatic cancer or IPMN.

Claims Coverage

The document contains one independent claim covering the core hsa-miR-33a* primer-based contacting, amplification to an amplification product, and measurement of hsa-miR-33a* expression level. Dependent claims further refine the inventive subject matter by adding additional miRNA biomarkers and specifying particular subtypes, sample-processing forms, and measurement readouts.

Across the independent claim and its dependents, the claim coverage centers on detecting hsa-miR-33a* by primer-specific contacting, amplification to an amplification product, and measuring expression level from the amplification product, with refinements that include additional miRNA biomarkers, combinations, pancreatic ductal adenocarcinoma, and primer-ligated cDNA processing with antisense-probe-based detection of sense target RNA.

Stated Advantages

Documented Applications