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EMT Molecular Signatures of Pancreatic Neuroendocrine Neoplasms
journal contributionposted on 2023-01-27, 02:20 authored by Abhi VenugopalAbhi Venugopal, Agnes MichalczykAgnes Michalczyk, Mustafa Khasraw, Leigh Ackland
Neuroendocrine neoplasms (NENs) are relatively rare neoplasms occurring predominantly in the gastrointestinal tract and pancreas. Their heterogeneity poses challenges for diagnosis and treatment. There is a paucity of markers for characterisation of NEN tumours. For routine diagnosis, immunohistochemistry of the NEN-specific markers CgA and synaptophysin and the proliferation marker Ki-67 are used. These parameters, however, are qualitative and lack the capacity to fully define the tumour phenotype. Molecules of epithelial–mesenchymal transition (EMT) are potential candidates for improved tumour characterisation. Using qRT-PCR, we measured mRNA levels of 27 tumour markers, including 25 EMT-associated markers, in tumour tissue and matched non-tumour tissues for 13 patients with pancreatic NENs. Tissue from patients with three different grades of tumour had distinctly different mRNA profiles. Of the 25 EMT-associated markers analysed, 17 were higher in G3 tissue relative to matched non-tumour tissue, including CD14, CD24, CD31, CD44, CD45, CD56, CK6, CK7, CK13, CK20, NSE, CDX2, CgA, DAXX, PCNA, laminin and Ki-67. The differences in levels of seven EMT-associated markers, Ki-67, DAXX, CD24, CD44, vimentin, laminin and PDX1 plus CgA and NSE (neuroendocrine markers) enabled a distinct molecular signature for each tumour grade to be generated. EMT molecules differentially expressed in three tumour grades have potential for use in tumour stratification and prognostication and as therapeutic targets for treatment of neuroendocrine cancers, following validation with additional samples.
JournalInternational Journal of Molecular Sciences
Article numberARTN 13645
Publication classificationC1 Refereed article in a scholarly journal
Science & TechnologyLife Sciences & BiomedicinePhysical SciencesBiochemistry & Molecular BiologyChemistry, MultidisciplinaryChemistryneuroendocrine neoplasms (NEN)biomarkersqRT-PCRimmunohistochemistryepithelial to mesenchymal transition (EMT)CHROMOGRANIN-ACELL-ADHESIONTUMORSEXPRESSIONMETASTASESENDOCRINECATENINPROTEINCAREHumansBiomarkers, TumorEpithelial-Mesenchymal TransitionKi-67 AntigenLamininPancreatic NeoplasmsRNA, MessengerRare DiseasesGeneticsDigestive DiseasesCancerPancreatic Cancer4.1 Discovery and preclinical testing of markers and technologies2.1 Biological and endogenous factorsSchool of Life and Environmental SciencesCentre for Cellular And Molecular BiologyFaculty of Science Engineering and Built EnvironmentChemical Sciences not elsewhere classifiedGeneticsBiological Sciences not elsewhere classified