Novel Biomarkers for Sub-Typing Pancreatic Ductal Adenocarcinoma
AssigneeHi-Stem Ggmbh
InventorsChristian Thomas Eisen, Andreas Trumpp, Martin Ronald Sprick
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Abstract
This invention relates to novel approaches for the identification and stratification of subtypes of pancreatic ductal adenocarcinoma (PDAC), in particular to novel PDAC subtype-specific markers, and to diagnostic kits comprising reagents for detecting said markers.
Claims27
In vitro method for the subtype-specific detection of PDAC cells in a tumor sample characterized by (A) the step of detecting expression of subtype-specific markers, either as proteins or as oligonucleotides encoding such proteins, wherein keratin 81 and vimentin are detected as markers for PDAC cells of the quasi-mesenchymal subtype, wherein (i) one or more transcription factors selected from HNF-1A, HNF-1B, FOXA2 (HNF3B), FOXA3 (HNF3G), HNF4G, and ONECUT1 (HNF6), (ii) one or more target genes regulated by HNF-1A, particularly the HNF-1A target genes listed in Table 2, and (iii) cadherin17 (CDH17) are detected as markers for cells of the exocrine-like subtype, and wherein PDAC cells of the classical subtype are characterized by the absence of (i) keratin 81 and/or vimentin, and (ii) HNF-1A and/or HNF-1B, or characterized by (B) the step of detecting expression of subtype-specific markers, either as proteins or as oligonucleotides encoding such proteins, wherein keratin 81 is the marker for PDAC cells of the quasi-mesenchymal subtype, wherein HNF-1A is the marker for cells of the exocrine-like subtype, and wherein PDAC cells of the classical subtype are characterized by the absence of keratin 81 and HNF-1A.
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In vitro method for the subtype-specific detection of PDAC cells in a tumor sample, characterized by the step of analyzing the Src inhibitor sensitivity signature in a gene expression profile, particularly wherein the gene expression profile is based on the set of 30 genes as shown in Table 1
Kit for the subtype-specific detection of PDAC cells comprising at least two reagents specific for PDAC subtype-specific markers selected from the list of:
- (i) keratin 81, (ii) vimentin, (iii) one or more transcription factors selected from HNF-1A, HNF-1B, FOXA2 (HNF3B), FOXA3 (HNF3G), HNF4G, and ONECUT1 (HNF6), (iv) one or more target genes regulated by HNF-1A, particularly the HNF-1A target genes listed in Table 2, and (v) cadherin17 (CDH17), wherein said reagents are selected from the list of:
- detection antibodies and oligonucleotide probes, and optionally further comprising at least one reagent for the detection of at least one of said reagents.
A kit for the subtype-specific detection of Src inhibitor-sensitive PDAC cells comprising oligonucleotide probes for the identification of a Src inhibitor sensitivity signature, particularly comprising oligonucleotide probes representing the 30 genes shown in Table 1.
A method of stratifying patients suffering from PDAC into treatment cohorts, the method comprising:
- (A) the steps of:
- (a) in vitro determination of (i) the expression and/or the presence of (i) keratin 81, (ii) vimentin, (iii) one or more transcription factors selected from HNF-1A, HNF-1B, FOXA2 (HNF3B), FOXA3 (HNF3G), HNF4G, and ONECUT1 (HNF6), (iv) one or more HNF-1A target genes, particularly the HNF-1A target genes listed in Table 2, and/or (v) cadherin17 (CDH17);
- (b) identifying the PDAC subtype based on the expression and/or the presence of the selected proteins;
- (c) stratifying PDAC patients into drug treatment cohorts based on the PDAC subtype they are suffering from;
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- (B) the steps of:
- (a) establishing an in vitro gene expression profile for the determination of the Src inhibitor sensitivity signature in cells of a patient sample containing pancreatic tissue;
- (b) identifying the PDAC subtype based on the gene expression profile;
- (c) stratifying PDAC patients into drug treatment cohorts based on the PDAC subtype they are suffering from.
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Dependencies are inferred from the claim text.