Molecular fingerprint of pre-tumor lesions of the pancreas discovereds. Just one study published in 'Nature Communications' by the research group of Giampaolo Tortora, professor of medical oncology at the Catholic University of the Sacred Heart and director of the Comprehensive Cancer Center of Gemelli Polyclinic in Rome, has identified specific tissue biomarkers – a sort of molecular fingerprint, in fact – which allow us to distinguish with certainty benign forms from those with a high degree of malignancy or at high risk of malignant transformation. A puzzle, so far, for doctors, given the difficulty in differentiating and recognizing which ones need to be monitored.
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To arrive at these results, researchers from Università Cattolica – Gemelli examined an incredible amount of data on surgical pieces of patients treated at Gemelli over the last ten years, making use of omics analyzes and in particular sophisticated spatial transcriptomic and proteomic technologies. .
Their work has made it possible to identify on tumor tissue the 'molecular signatures' that indicate low-grade dysplasia (Hoxb3 and Znf117), those of 'borderline' cases (Spdef) and finally the markers of high-grade dysplasia, i.e. forms definitely malignant (Nkx6-2). Not only. This research also sheds light on the role of the activation of some genes (TnfAlpha and Myc) in the progression of intraductal papillary mucinous tumors (Ipnm) from a benign to a malignant form (ductal pancreatic adenocarcinoma, or Pdac).
“Up to now, the risk stratification of IPNMs – explains Tortora – is done only on the basis of clinical characteristics (especially those at high risk are IPNMs that develop in the main ducts) and radiological (CT scan, MRI), while no criteria were available. that took their biology into account. This means that up to 10% of IPNMs considered at low risk – admits the expert – escape correct evaluation and, over time, can give rise to an aggressive tumor”. The research just published was supported by a grant from the Airc Foundation, assigned to the project of Carmine Carbone, team leader of the study and researcher at the Agostino Gemelli Irccs University Polyclinic Foundation.
The pancreatic intraductal papillary mucinous neoplasms – explain the Gemini experts – they are cystic lesions which develop inside the pancreatic ducts and which contain 'shoots' of tissue (papillary projections) lined with mucous epithelium. The frequency of these cysts with uncertain behavior, which are discovered by chance during a CT scan or MRI done for another reason, is increasing and grows with advancing age. A recent meta-analysis by the Mayo Clinic (USA) reveals that IPMNs are discovered by chance in approximately 11% of over-50s undergoing abdominal CT scans. However, certain data on prevalence and incidence are lacking. “An absolute necessity is to create an Italian register of IPNMs – underlines Tortora – because we are certain that their number is widely underestimated”.
These tumors arise from the pancreatic ducts and are considered precursors of pancreatic ductal adenocarcinoma, an extremely aggressive neoplasm, against which there are limited therapeutic options. Which ones will evolve in this direction? The research conducted at Cattolica and Gemelli makes a contribution to the identification of lesions with a high potential for malignant transformation. “And this is an important indication – remarks Tortora – because if it is fundamental to identify the lesions at high risk of malignant transformation, it is equally crucial to define the characteristics of 'benignity', to avoid patients having a useless, very invasive and not without risks.”
A precision diagnosis. “With a patient and meticulous study of transcriptomics and spatial proteomics carried out on tissue (i.e. on the operating piece) – reconstructs Carbone – we analyzed the cells that make up the Ipmn one by one to study the RNA and the corresponding proteins, respecting the cytoarchitecture of the tissue. Thus it was possible to highlight that the forms with a lower or greater risk of malignant transformation differ in the expression of some genes and proteins. In particular, the expression of the Nkx6-2 gene confers an increased risk of malignant differentiation; in contrast, the expression of the Hoxb3 and Znf117 genes indicates low-grade dysplasia, a benign condition. The next step will consist in the search for a prognostic biomarker of tumor transformation in the blood.” And in the future “we could hypothesize the development of treatments capable of blocking the molecular 'pathways' through which the transformation of a pre-cancerous lesion into a tumor travels: an anti-Myc is already being studied. But there is more. With theranostics we could try to conjugate an antibody targeted against Nkx6-2 with a radiopharmaceutical to precisely target, exploiting the 'good nuclear', the tumor cells that express this gene, an index of malignancy”, concludes Carbone .
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